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  • Influenza A virus polymerase: an attractive target for next-generation anti-influenza therapeutics
    Drug. Discov. Today (IF 6.369) Pub Date : 2018-01-12
    Zhongxia Zhou, Tao Liu, Jian Zhang, Peng Zhan, Xinyong Liu

    The influenza RNA-dependent RNA polymerase (RdRP) is conserved among different types of influenza virus, playing an important part in transcription and replication. In this regard, influenza RdRP is an attractive target for novel anti-influenza drug discovery. Herein, we will introduce the structural and functional information of influenza polymerase; and an overview of inhibitors targeting the PA endonuclease and PB2 cap-binding site is provided, along with the approaches utilized for identification of these inhibitors. The protein–protein interactions (PPIs) of the three polymerase subunits: PA, PB1 and PB2, are described based on the published crystal structures, and inhibitors targeting the PA–PB1 interaction are introduced briefly.

    更新日期:2018-01-12
  • Safinamide: a new hope for Parkinson’s disease?
    Drug. Discov. Today (IF 6.369) Pub Date : 2018-01-12
    Fábio G. Teixeira, Miguel F. Gago, Paulo Marques, Pedro Silva Moreira, Ricardo Magalhães, Nuno Sousa, António J. Salgado

    The loss of dopaminergic neurons (DAn) and reduced dopamine (DA) production underlies the reasoning behind the gold standard treatment for Parkinson’s disease (PD) using levodopa (L-DOPA). Recently licensed by the European Medicine Agency (EMA) and US Food and Drug Administration (FDA), safinamide [a monoamine oxidase B (MOA-B) inhibitor] is an alternative to L-DOPA; as we discuss here, it enhances dopaminergic transmission with decreased secondary effects compared with L-DOPA. In addition, nondopaminergic actions (neuroprotective effects) have been reported, with safinamide inhibiting glutamate release and sodium/calcium channels, reducing the excitotoxic input to dopaminergic neuronal death. Effects of safinamide have been correlated with the amelioration of non-motor symptoms (NMS), although these remain under discussion. Overall, safinamide can be considered to have potential antidyskinetic and neuroprotective effects and future trials and/or studies should be performed to provide further evidence for its potential as an anti-PD drug.

    更新日期:2018-01-12
  • Mimicking the 3D biology of osteochondral tissue with microfluidic-based solutions: breakthroughs towards boosting drug testing and discovery
    Drug. Discov. Today (IF 6.369) Pub Date : 2018-01-12
    Mariana R. Carvalho, Rui Luís Reis, Joaquim Miguel Oliveira

    The development of tissue-engineering (TE) solutions for osteochondral (OC) regeneration has been slowed by technical hurdles related to the recapitulation of their complex and hierarchical architecture. OC defects refer to damage of both the articular cartilage and the underlying subchondral bone. To repair an OC tissue defect, the complexity of the bone and cartilage must be considered. To help achieve this, microfluidics is converging with TE approaches to provide new treatment possibilities. Microfluidics uses precise micrometer-to-millimeter-scale fluid flows to achieve high-resolution and spatial and/or temporal control of the cell microenvironment, providing powerful tools for cell culturing. Herein, we overview the progress of microfluidics for developing 3D in vitro models of OC tissue, with a focus on cancer bone metastasis.

    更新日期:2018-01-12
  • Designing an intuitive web application for drug discovery scientists
    Drug. Discov. Today (IF 6.369) Pub Date : 2018-01-11
    Nikiforos Karamanis, Miguel Pignatelli, Denise Carvalho-Silva, Francis Rowland, Jennifer A. Cham, Ian Dunham
    更新日期:2018-01-12
  • Progress with covalent small-molecule kinase inhibitors
    Drug. Discov. Today (IF 6.369) Pub Date : 2018-01-11
    Zheng Zhao, Philip E. Bourne

    With reduced risk of toxicity and high selectivity, covalent small-molecule kinase inhibitors (CSKIs) have emerged rapidly. Through the lens of structural system pharmacology, here we review this rapid progress by considering design strategies and the challenges and opportunities offered by current CSKIs.

    更新日期:2018-01-12
  • On the glycosylation aspects of biosimilarity
    Drug. Discov. Today (IF 6.369) Pub Date : 2018-01-11
    László Hajba, Ákos Szekrényes, Beáta Borza, András Guttman

    The recent expiration of several protein therapeutics opened the door for biosimilar development. Biosimilars are biologic medical products that are similar but not identical copies of already-authorized protein therapeutics. Critical quality attributes (CQA), such as post-translational modifications of recombinant biotherapeutics, are important for the clinical efficacy and safety of both the innovative biologics and their biosimilar counterparts. Here, we summarize biosimilarity CQAs, considering the regulatory guidelines and the statistical aspects (e.g., biosimilarity index) and then discuss glycosylation as one of the important attributes of biosimilarity. Finally, we introduced the ‘Glycosimilarity Index’, which is based on the averaged biosimilarity criterion.

    更新日期:2018-01-12
  • Stem cells as vehicles and targets of nanoparticles
    Drug. Discov. Today (IF 6.369) Pub Date : 2018-01-11
    Sónia Pinho, Maria H. Macedo, Catarina Rebelo, Bruno Sarmento, Lino Ferreira

    Modulation of endogenous adult stem cell niches represents a promising strategy for regeneration of tissues and to correct cell abnormalities, including cancer. Recent advances show the possibility to target endogenous stem cells or their progenies by using nanoparticles conjugated with specific biomolecules. In addition, the targeting of the stem cell niche can be accomplished by using stem cells loaded with nanoparticles. This review examines principles for the targeting of endogenous stem cells as well as factors for the modulation of stem cells.

    更新日期:2018-01-12
  • The positive impacts of Real-World Data on the challenges facing the evolution of biopharma
    Drug. Discov. Today (IF 6.369) Pub Date : 2018-01-11
    John Wise, Angeli Möller, David Christie, Dipak Kalra, Elia Brodsky, Evelina Georgieva, Greg Jones, Ian Smith, Lars Greiffenberg, Marie McCarthy, Michael Arend, Olivier Luttringer, Sebastian Kloss, Steve Arlington

    Demand for healthcare services is unprecedented. Society is struggling to afford the cost. Pricing of biopharmaceutical products is under scrutiny, especially by payers and Health Technology Assessment agencies. As we discuss here, rapidly advancing technologies, such Real-World Data (RWD), are being utilized to increase understanding of disease. RWD, when captured and analyzed, produces the Real-World Evidence (RWE) that underpins the economic case for innovative medicines. Furthermore, RWD can inform the understanding of disease, help identify new therapeutic intervention points, and improve the efficiency of research and development (R&D), especially clinical trials. Pursuing precompetitive collaborations to define shared requirements for the use of RWD would equip service-providers with the specifications needed to implement cloud-based solutions for RWD acquisition, management and analysis. Only this approach would deliver cost-effective solutions to an industry-wide problem.

    更新日期:2018-01-12
  • Increasing mtDNA levels as therapy for mitochondrial optic neuropathies
    Drug. Discov. Today (IF 6.369) Pub Date : 2018-01-11
    Eduardo Ruiz-Pesini, Sonia Emperador, Ester López-Gallardo, Carmen Hernandez-Ainsa, Julio Montoya

    Leber hereditary optic neuropathy (LHON) is a rare, inherited mitochondrial disease. No treatment has shown a clear-cut benefit on a clinically meaningful end-point. Primary open-angle glaucoma is a frequent, acquired optic neuropathy. Lowering intraocular pressure reduces disease progression. However, current methods to decelerate this progression are recognized as being inadequate. Therefore, there is a clear need to look for new therapeutic approaches. The growing evidence indicates that primary open-angle glaucoma can also be a mitochondrial optic neuropathy (MON). Several risk elements are common for both diseases and all of them decrease mitochondrial (mt)DNA content. Based on these susceptibility factors and their molecular mechanism, we suggest herein pharmacological therapies targeted to increase mtDNA levels, oxidative phosphorylation capability, and mitochondrial energy production as treatments for MONs.

    更新日期:2018-01-12
  • Incorporating upper motor neuron health in ALS drug discovery
    Drug. Discov. Today (IF 6.369) Pub Date : 2018-01-10
    Ina Dervishi, P.Hande Ozdinler

    Amyotrophic lateral sclerosis (ALS) is a complex disease, affecting the motor neuron circuitry. After consecutive failures in clinical trials for the past 20 years, edaravone was recently approved as the second drug for ALS. This generated excitement in the field and revealed the need to improve preclinical assays for continued success. Here, we focus on the importance and relevance of upper motor neuron (UMN) pathology in ALS, and discuss how incorporation of UMN survival in preclinical assays will improve inclusion criteria for clinical trials and expedite the drug discovery effort in ALS and related motor neuron diseases.

    更新日期:2018-01-11
  • Peripheral modulation of the endocannabinoid system in metabolic disease
    Drug. Discov. Today (IF 6.369) Pub Date : 2018-01-10
    Nirajan Shrestha, James S.M. Cuffe, Dana S. Hutchinson, John P. Headrick, Anthony V. Perkins, Andrew J. McAinch, Deanne H. Hryciw

    Dysfunction of the endocannabinoid system (ECS) has been identified in metabolic disease. Cannabinoid receptor 1 (CB1) is abundantly expressed in the brain but also expressed in the periphery. Cannabinoid receptor 2 (CB2) is more abundant in the periphery, including the immune cells. In obesity, global antagonism of overexpressed CB1 reduces bodyweight but leads to centrally mediated adverse psychological outcomes. Emerging research in isolated cultured cells or tissues has demonstrated that targeting the endocannabinoid system in the periphery alleviates the pathologies associated with metabolic disease. Further, peripheral specific cannabinoid ligands can reverse aspects of the metabolic phenotype. This Keynote review will focus on current research on the functionality of peripheral modulation of the ECS for the treatment of obesity.

    更新日期:2018-01-11
  • The hitchhiker’s guide to the chemical-biological galaxy
    Drug. Discov. Today (IF 6.369) Pub Date : 2018-01-09
    Giulia Opassi, Alessandro Gesù, Alberto Massarotti
    更新日期:2018-01-10
  • A bibliometric review of drug repurposing
    Drug. Discov. Today (IF 6.369) Pub Date : 2018-01-09
    Nancy C. Baker, Sean Ekins, Antony J. Williams, Alexander Tropsha

    We have conducted a bibliometric review of drug repurposing by scanning >25 million papers in PubMed and using text-mining methods to gather, count and analyze chemical–disease therapeutic relationships. We find that >60% of the ∼35 000 drugs or drug candidates identified in our study have been tried in more than one disease, including 189 drugs that have been tried in >300 diseases each. Whereas in the majority of cases these drugs were applied in therapeutic areas close to their original use, there have been striking, and perhaps instructive, successful attempts of drug repurposing for unexpected, novel therapeutic areas.

    更新日期:2018-01-10
  • Recent progress in the discovery of myeloid differentiation 2 (MD2) modulators for inflammatory diseases
    Drug. Discov. Today (IF 6.369) Pub Date : 2018-01-09
    Lingfeng Chen, Weitao Fu, Lulu Zheng, Yi Wang, Guang Liang

    Myeloid differentiation protein 2 (MD2), together with Toll-like receptor 4 (TLR4), binds lipopolysaccharide (LPS) with high affinity, inducing the formation of the activated homodimer LPS-MD2-TLR4. MD2 directly recognizes the Lipid A domain of LPS, leading to the activation of downstream signaling of cytokine and chemokine production, and initiation of inflammatory and immune responses. However, excessive activation and potent host responses generate severe inflammatory syndromes such as acute sepsis and septic shock. MD2 is increasingly being considered as an attractive pharmacological target for the development of potent anti-inflammatory agents. In this Keynote review, we provide a comprehensive overview of the recent advances in the structure and biology of MD2, and present MD2 modulators as promising agents for anti-inflammatory intervention.

    更新日期:2018-01-10
  • Present drug-likeness filters in medicinal chemistry during the hit and lead optimization process: how far can they be simplified?
    Drug. Discov. Today (IF 6.369) Pub Date : 2018-01-09
    Serge Mignani, João Rodrigues, Helena Tomas, Rachid Jalal, Parvinder Pal Singh, Jean-Pierre Majoral, Ram A. Vishwakarma
    更新日期:2018-01-10
  • An update on the role of nanovehicles in nose-to-brain drug delivery
    Drug. Discov. Today (IF 6.369) Pub Date : 2018-01-09
    Yunhai Feng, Haisheng He, Fengqian Li, Yi Lu, Jianping Qi, Wei Wu

    A quantitative analysis has cast doubt over the limited advantages provided by particles for nose-to-brain (NTB) drug delivery. Thus, it is imperative to identify the role of nanovehicles in NTB drug delivery. If nanocarriers are used merely as an option to improve various properties of the drugs or the formulations, it is difficult for them to outperform conventional formulations, such as solutions or gels. However, nanovehicles bring about special features, such as maintenance of the solubilized state of drugs, sustained or delayed release, and enhanced penetration because of surface modifications, all of which lead to enhanced NTB delivery efficiency.

    更新日期:2018-01-10
  • Privileged portal metastasis of hepatocellular carcinoma in light of the coevolution of a visceral portal system and liver in the chordate lineage: a search for therapeutic targets
    Drug. Discov. Today (IF 6.369) Pub Date : 2018-01-09
    Vladimir M. Subbotin

    Hepatocellular carcinoma (HCC) disseminates systemically, but metastases occur in distant organs in only a few patients, whereas HCC routinely metastasizes to liver and its vessels. HCC cells disseminate via hepatic veins, but portal veins are affected by metastasis more frequently than are hepatic veins, and correlates with poor prognosis. In this review, I suggest that privileged HCC portal metastasis occurs because of high levels of pancreatic family hormones and growth factors (PHGFs) in the portal blood. The analysis suggests that the appearance of the portal system carrying PHGFs in the evolution of invertebrate chordate (Amphioxus) led to the evolution of the liver in vertebrate; given that the portal pattern of HCC metastasis and selection of more-aggressive clones are PHGF dependent, PHGFs and their ligands constitute therapeutic targets.

    更新日期:2018-01-10
  • Manipulating the epigenome for the treatment of disorders with thrombotic complications
    Drug. Discov. Today (IF 6.369) Pub Date : 2018-01-09
    Faith A.A. Kwa, Denise E. Jackson

    The haemostatic system is tightly regulated to maintain homeostasis to avoid unwanted bleeding or thrombotic complications. Recent research has highlighted the importance of epigenetic changes, such as DNA methylation, histone modifications, and miRNA-based mechanisms, that alter gene expression. This can give rise to dysregulated haemostatic or vascular expressed molecules contributing to the development of thrombotic complications. Targeting these epigenetic changes could provide a new avenue for the treatment of pathological blood clots. However, the lack of tissue specificity warrants high-resolution genomic studies of the transcriptome and methylome that will reveal explicit epigenetic targets for the design of superior drugs with minimum off-target effects.

    更新日期:2018-01-10
  • Unlocking the full potential of open innovation in the life sciences through a classification system
    Drug. Discov. Today (IF 6.369) Pub Date : 2018-01-08
    Niclas Nilsson, Timo Minssen

    A common understanding of expectations and requirements is critical for boosting research-driven business opportunities in open innovation (OI) settings. Transparent communication requires common definitions and standards for OI to align the expectations of both parties. Here, we suggest a five-level classification system for OI models, reflecting the degree of openness. The aim of this classification system is to reduce contract negotiation complexity and times between two parties looking to engage in OI. Systematizing definitions and contractual terms for OI in the life sciences helps to reduce entry barriers and boosts collaborative value generation. By providing a contractual framework with predefined rules, science will be allowed to move more freely, thus maximizing the potential of OI.

    更新日期:2018-01-09
  • Use of CRISPR/Cas9 gene-editing tools for developing models in drug discovery
    Drug. Discov. Today (IF 6.369) Pub Date : 2018-01-08
    Gulzar Ahmad, Mansoor Amiji

    Clustered regularly interspaced short palindromic repeat/CRISPR-associated 9 (CRISPR/Cas9) enables targeted genome engineering. The simplicity of this system, its facile engineering, and amenability to multiplex genes make it the system of choice for many applications. This system has revolutionized our ability to carry out gene editing, transcription regulation, genome imaging, and epigenetic modification. In this review, we discuss the discovery of CRISPR/Cas9, its mechanism of action, its application in medicine and animal model development, and its delivery. We also highlight how the CRISPR/Cas9 system can affect the next generation of drugs by accelerating the identification and validation of high-value targets. The generation of precision disease models through this system will provide a rapid avenue for functional drug screening.

    更新日期:2018-01-09
  • Light-triggerable formulations for the intracellular controlled release of biomolecules
    Drug. Discov. Today (IF 6.369) Pub Date : 2018-01-08
    Miguel M. Lino, Lino Ferreira

    New therapies based on the use of biomolecules [e.g., proteins, peptides, and non-coding (nc)RNAs] have emerged during the past few years. Given their instability, adverse effects, and limited ability to cross cell membranes, delivery systems are required to fully reveal their biological potential. Sophisticated nanoformulations responsive to light offer an excellent opportunity for the controlled release of these biomolecules, enabling the control of timing, duration, location, and dosage. In this review, we discuss the design principles for the delivery of biomolecules, in particular proteins and RNA-based therapeutics, by light-triggerable formulations. We further discuss the opportunities offered by these formulations in terms of endosomal escape, as well as their limitations.

    更新日期:2018-01-09
  • Pharmaceutical nanocrystals: production by wet milling and applications
    Drug. Discov. Today (IF 6.369) Pub Date : 2018-01-08
    Maria Malamatari, Kevin M.G. Taylor, Stavros Malamataris, Dennis Douroumis, Kyriakos Kachrimanis

    Nanocrystals are regarded as an important nanoformulation approach exhibiting advantages of increased dissolution and saturation solubility with chemical stability and low toxicity. Nanocrystals are produced in the form of nanosuspensions using top-down (e.g., wet milling or high pressure homogenization) and bottom-up methods (e.g., antisolvent precipitation). Wet milling is a scalable method applicable to drugs with different physicochemical and mechanical properties. Nanocrystalline-based formulations, either as liquid nanosuspensions or after downstream processing to solid dosage forms, have been developed as drug delivery systems for various routes of administration (i.e., oral, parenteral, pulmonary, ocular, and dermal). In this review, we summarize and discuss the features, preparation methods, and therapeutic applications of pharmaceutical nanocrystals, highlighting their universality as a formulation approach for poorly soluble drugs.

    更新日期:2018-01-09
  • NCp7: targeting a multitask protein for next-generation anti-HIV drug development part 2. Noncovalent inhibitors and nucleic acid binders
    Drug. Discov. Today (IF 6.369) Pub Date : 2018-01-08
    Nunzio Iraci, Oriana Tabarrini, Claudio Santi, Luca Sancineto

    Nucleocapsid protein 7 (NCp7) represents a viable target not yet reached by the currently available antiretrovirals. It is a small and highly basic protein, which is essential for multiple stages of the viral replicative cycle, with its structure preserved in all viral strains, including clinical isolates. NCp7 can be inhibited covalently, noncovalently and by shielding the nucleic acid (NA) substrates of its chaperone activity. Although covalent NCp7 inhibitors have already been detailed in the first part of this review series, the focus here is based on noncovalent and NA-binder inhibitors and on the analysis of the NCp7 3D structure to deliver fruitful insights for future drug design strategies.

    更新日期:2018-01-09
  • Macromolecule nanotherapeutics: approaches and challenges
    Drug. Discov. Today (IF 6.369) Pub Date : 2018-01-08
    Puneet Tyagi, Jose Luis Santos
    更新日期:2018-01-09
  • Mechanism of nanoparticle-induced hypersensitivity in pigs: complement or not complement?
    Drug. Discov. Today (IF 6.369) Pub Date : 2018-01-08
    János Szebeni

    A recent study on nanoparticle-induced hypersensitivity reactions in pigs showed robust pulmonary intravascular macrophage clearance of Polybead® carboxylate microspheres in mediating the adverse cardiopulmonary distress, irrespective of the ability of these particles to activate the Complement (C) system in vitro. Focusing on this observation, this article highlights the controversies in projecting in vitro C assay data to in vivo conditions and applying data on polystyrene particles to therapeutic nanopharmaceuticals. Based on overwhelming evidence of a role of anaphylatoxins in hypersensitivity reactions, the need to further explore the role of C activation in the reported and other reactions is highlighted. C-activation-related and C-independent pseudoallergies (CARPA and CIPA) can proceed simultaneously, as outlined by the ‘double-hit’ hypothesis.

    更新日期:2018-01-09
  • Phage-derived lysins as potential agents for eradicating biofilms and persisters
    Drug. Discov. Today (IF 6.369) Pub Date : 2018-01-08
    Umender Sharma, Aradhana Vipra, Shankaramurthy Channabasappa

    Bacterial biofilms are highly resistant to the action of antibiotics. Presence of persisters, phenotypically resistant populations of bacterial cells, is thought to contribute toward recalcitrance of biofilms. The phage-derived lysins, by virtue of their ability to cleave the peptidoglycan of bacterial cells in an enzymatic manner, have the unique ability to kill dormant cells. Several lysins have shown potent antibiofilm activity in vitro. The fact that lysins have shown better efficacy than conventional drugs in animal models of endocarditis and other infections involving biofilms suggests that the lysins can potentially be developed against difficult-to-treat bacterial infections.

    更新日期:2018-01-09
  • Ligandomics: a paradigm shift in biological drug discovery
    Drug. Discov. Today (IF 6.369) Pub Date : 2018-01-08
    Wei Li, Iok-Hou Pang, Mario Thiego F. Pacheco, Hong Tian
    更新日期:2018-01-09
  • Overcoming the resistance mechanisms of Smoothened inhibitors
    Drug. Discov. Today (IF 6.369) Pub Date : 2018-01-08
    Xiaochun Dong, Chenglin Wang, Zhongjian Chen, Weili Zhao

    Smoothened (Smo), the main transducer of the Hedgehog (Hh) signaling pathway, is a promising target for anticancer therapy. Although vismodegib and sonidegib have demonstrated effectiveness for the treatment of basal cell carcinoma (BCC), their clinical use has been associated with mutation-related drug resistance. In this review, we outline the resistance mechanisms of Smo inhibitors and point the way for future endeavors. We focus in particular on the development of second-generation Smo inhibitors based on co-crystal structures, inhibition of downstream components, and the regulation of other interacting pathways or mediators that could compensate for the inhibitory activity of upstream inhibitors.

    更新日期:2018-01-09
  • Administration of antioxidants in cancer: debate of the decade
    Drug. Discov. Today (IF 6.369) Pub Date : 2018-01-06
    Rajneet Kaur Khurana, Ashay Jain, Atul Jain, Teenu Sharma, Bhupinder Singh, Prashant Kesharwani

    Several randomized clinical trials have divulged that administration of antioxidants during chemotherapy decreases the effectiveness of treatment. Hence, the characteristic feature of this article is extensive assessment of putative benefits and potential risks of natural and synthetic antioxidant supplementation, administered with chemotherapy, based upon the available preclinical and clinical data. After analyzing mixed results, it was concluded that current FDA guidelines should be followed before supplementing antioxidants during cytotoxic treatment. Nevertheless, contradictory experimental animal models opposing human clinical trials discourage the concurrent administration of antioxidants ostensibly owing to the possibility of tumor protection and reduced survival.

    更新日期:2018-01-07
  • Astrocytes as targets for drug discovery
    Drug. Discov. Today (IF 6.369) Pub Date : 2018-01-06
    Kirill Gorshkov, Francis Aguisanda, Natasha Thorne, Wei Zheng

    Recent studies have illuminated the crucial role of astrocytes in maintaining proper neuronal health and function. Abnormalities in astrocytic functions have now been implicated in the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS). Historically, drug development programs for neurodegenerative diseases generally target only neurons, overlooking the contributions of astrocytes. Therefore, targeting both disease neurons and astrocytes offers a new approach for drug development for the treatment of neurological diseases. Looking forward, the co-culturing of human neurons with astrocytes could be the next evolutionary step in drug discovery for neurodegenerative diseases.

    更新日期:2018-01-06
  • From clinical proof-of-concept to commercialization of CAR T cells
    Drug. Discov. Today (IF 6.369) Pub Date : 2018-01-06
    Boris Calmels, Bechara Mfarrej, Christian Chabannon

    The development of CAR T cells currently represents an exciting opportunity to convert the already published clinical successes observed in clinical trials into commercially available efficient therapies. However, the path toward successful commercialization is still hindered by many hurdles. Here, we review such issues as: the need for structured collaborations between hospital collection and clinical facilities and industry manufacturing facilities to streamline the supply chain; necessity for uniform and efficient medical procedures to cope with severe toxicities associated with CAR T cells; and absolute need to define an economical and sustainable model for manufacturers and payers. The fast pace at which the field is evolving requires careful assessments for the benefit of patients.

    更新日期:2018-01-06
  • The microRNA landscape of cutaneous squamous cell carcinoma
    Drug. Discov. Today (IF 6.369) Pub Date : 2018-01-06
    Kathryn Konicke, Argelia Lopez, José Luis Muñoz, Luis Steven Servin, Armando Flores, Edit Olasz, Zelmira Lazarova

    Cutaneous squamous cell carcinoma (cSCC) is a keratinocyte-derived skin tumor. It is the second-most-common cancer affecting the Caucasian population and is responsible for >20% of all skin-cancer-related deaths. The estimated incidence of non-melanoma skin cancer in the USA is >1 000 000 cases per year, of which roughly 20–30% are squamous cell carcinoma. To better understand and treat this challenging cancer, current research focuses on development of novel strategies to improve the understanding of tumor biogenesis on an individual basis. microRNAs are becoming important biomarkers in the diagnosis, prognosis and treatment of cSCC. This review describes the current knowledge on miRNA expression in cSCC and its role as a biomarker for personalized medicine.

    更新日期:2018-01-06
  • Pathway-based technologies for early drug discovery
    Drug. Discov. Today (IF 6.369) Pub Date : 2017-12-30
    Chris Fotis, Asier Antoranz, Dimitris Hatziavramidis, Theodore Sakellaropoulos, Leonidas G. Alexopoulos
    更新日期:2017-12-31
  • Real world big data for clinical research and drug development
    Drug. Discov. Today (IF 6.369) Pub Date : 2017-12-30
    Gurparkash Singh, Duane Schulthess, Nigel Hughes, Bart Vannieuwenhuyse, Dipak Kalra

    The objective of this paper is to identify the extent to which real world data (RWD) is being utilized, or could be utilized, at scale in drug development. Through screening peer-reviewed literature, we have cited specific examples where RWD can be used for biomarker discovery or validation, gaining a new understanding of a disease or disease associations, discovering new markers for patient stratification and targeted therapies, new markers for identifying persons with a disease, and pharmacovigilance. None of the papers meeting our criteria was specifically geared toward new novel targets or indications in the biopharmaceutical sector; the majority were focused on the area of public health, often sponsored by universities, insurance providers or in combination with public health bodies such as national insurers. The field is still in an early phase of practical application, and is being harnessed broadly where it serves the most direct need in public health applications in early, rare and novel disease incidents. However, these exemplars provide a valuable contribution to insights on the use of RWD to create novel, faster and less invasive approaches to advance disease understanding and biomarker discovery. We believe that pharma needs to invest in making better use of EHRs and the need for more precompetitive collaboration to grow the scale of this ‘big denominator’ capability, especially given the needs of precision medicine research.

    更新日期:2017-12-31
  • One-Size-Fits-All Dosing in Oncology Wastes Money, Innovation and Lives
    Drug. Discov. Today (IF 6.369) Pub Date : 2017-11-21
    David C. Norris

    Failure to individualize drug dosing may waste 50% of the value of pharmaceutical innovation coming off the bench, driving the unacceptable failure rates of drug development programs and unsustainable drug costs. An immense opportunity is thus presented to investors in pharmaceutical innovation who are willing to develop and field innovative Phase 1 trial methodologies that solve this problem. The principle of Dose Titration Algorithm Tuning (DTAT) offers a reasoned strategy for accomplishing this. Image for unlabelled figure Figure options

    更新日期:2017-11-21
  • Recent advances in bacteriophage-based methods for bacteria detection
    Drug. Discov. Today (IF 6.369) Pub Date : 2017-11-20
    Łukasz Richter, Marta Janczuk-Richter, Joanna Niedziółka-Jönsson, Jan Paczesny, Robert Hołyst

    Fast and reliable bacteria detection is crucial for lowering the socioeconomic burden related to bacterial infections (e.g., in healthcare, industry or security). Bacteriophages (i.e., viruses with bacterial hosts) pose advantages such as great specificity, robustness, toughness and cheap preparation, making them popular biorecognition elements in biosensors and other assays for bacteria detection. There are several possible designs of bacteriophage-based biosensors. Here, we focus on developments based on whole virions as recognition agents. We divide the review into sections dealing with phage lysis as an analytical signal, phages as capturing elements in assays and phage-based sensing layers, putting the main focus on development reported within the past three years but without omitting the fundamentals.

    更新日期:2017-11-20
  • Understanding missing proteins: a functional perspective
    Drug. Discov. Today (IF 6.369) Pub Date : 2017-11-20
    Longjian Zhou, Limsoon Wong, Wilson Wen Bin Goh

    A missing protein (MP) is an unconfirmed genetic sequence for which a protein product is not yet detected. Currently, MPs are tiered based on supporting evidence mainly in the form of protein existence (PE) classification. As we discuss here, this definition is overly restrictive because proteins go missing in day-to-day proteomics as a result of low abundance, lack of sequence specificity, splice variants, and so on. Thus, we propose a broader functional classification of MPs that complements PE classification, discuss major causes, and examine three corresponding solution tiers:. biological, technical, and informatics. We assert that informatics-driven solutions would have a major role in resolving the MP problem (MPP).

    更新日期:2017-11-20
  • Applications of stimuli-responsive nanoscale drug delivery systems in translational research
    Drug. Discov. Today (IF 6.369) Pub Date : 2017-11-16
    Mengjie Gu, Xin Wang, Tan Boon Toh, Edward Kai-Hua Chow

    Nanoscale drug delivery systems or nanocarriers have shown tremendous promise in the target-specific delivery of therapeutics as well as diagnostic agents. Additional properties can be introduced into nanocarriers to enhance the bioavailability and targeting efficiency of the transported drugs at diseased sites. Such nanocarriers are usually incorporated with stimuli-responsive components that can be triggered by specific stimuli (e.g., temperature, pH, or enzymes) and further induced by certain biological responses, such as enzyme hydrolysis and molecular conformational changes, leading to the controlled release of the transported molecules at targeted sites. In this review, we discuss various stimuli-responsive nanoscale delivery systems and summarize the current perspectives as well as challenges facing the successful translation of these innovative stimuli-responsive nanocarriers from the bench to the bedside.

    更新日期:2017-11-20
  • Personalized nanomedicine for CNS diseases
    Drug. Discov. Today (IF 6.369) Pub Date : 2017-11-15
    Ajeet Kaushik, Rahul Dev Jayant, Vinay Bhardwaj, Madhavan Nair

    Central nervous system (CNS) diseases are rapidly increasing globally. Currently used therapeutic agents to treat CNS diseases exhibit significant efficacy. However, the inability of these drugs to cross the blood–brain barrier (BBB) and invasiveness of the technologies to achieve localized drug delivery in disease-specific parts of the brain have thwarted pain-free and complete treatment of CNS diseases. Therefore, the safe, non-invasive, and targeted delivery of drugs to the brain using nanoparticles (NPs) is currently receiving considerable research attention. Here, we highlight advances in state-of-the-art personalized nanomedicine for the treatment of CNS diseases (with a focus on dementia), the related challenges, possible solutions, and prospects for nano-enabled personalized medicine.

    更新日期:2017-11-17
  • The role of fMRI in drug development
    Drug. Discov. Today (IF 6.369) Pub Date : 2017-11-15
    Owen Carmichael, Adam J. Schwarz, Christopher H. Chatham, David Scott, Jessica A. Turner, Jaymin Upadhyay, Alexandre Coimbra, James A. Goodman, Richard Baumgartner, Brett A. English, John W. Apolzan, Preetham Shankapal, Keely R. Hawkins

    Functional magnetic resonance imaging (fMRI) has been known for over a decade to have the potential to greatly enhance the process of developing novel therapeutic drugs for prevalent health conditions. However, the use of fMRI in drug development continues to be relatively limited because of a variety of technical, biological, and strategic barriers that continue to limit progress. Here, we briefly review the roles that fMRI can have in the drug development process and the requirements it must meet to be useful in this setting. We then provide an update on our current understanding of the strengths and limitations of fMRI as a tool for drug developers and recommend activities to enhance its utility.

    更新日期:2017-11-17
  • Nanomedicine safety in preclinical and clinical development: focus on idiosyncratic injection/infusion reactions
    Drug. Discov. Today (IF 6.369) Pub Date : 2017-11-13
    S.M. Moghimi

    Injection/infusion reactions to nanopharmaceuticals (and particulate drug carriers) are idiosyncratic and well documented. The molecular basis of nanoparticle-mediated injection reactions is debatable, with two hypotheses as front-runners. The first is complement-activation-related ‘pseudoallergy’, where a causal role for nanoparticle-mediated complement activation in injection/infusion reactions is considered. However, the second hypothesis (the rapid phagocytic response hypothesis) states a transitional link from robust clearance of nanoparticles (NPs) from the blood by strategically placed responsive macrophages to adverse hemodynamic and cardiopulmonary reactions, regardless of complement activation. Here, I critically examine and discuss these hypotheses. Current experimentally derived evidence appears to be more in support of the rapid phagocytic response hypothesis than of the pseudoallergy hypothesis.

    更新日期:2017-11-14
  • Galectin-3: mediator of microglia responses in injured brain
    Drug. Discov. Today (IF 6.369) Pub Date : 2017-11-10
    Reza Rahimian, Louis-Charles Béland, Jasna Kriz

    Galectin-3 is a pleiotropic protein involved in cell activation, proliferation and migration and plays a pivotal part as an inflammatory mediator in neurodegeneration. Galectin-3 is associated with microglial activation and proliferation after ischemia. Given its putative role as a dynamic fine-tuner of microglia, activation of Galectin-3 provides molecular cues in design of new immunomodulatory strategies for stroke management. This review summarizes recent evidence on the role of Galectin-3 as a mediator of immune responses in damaged brain and mechanisms employed by Galectin-3 to affect microglial function.

    更新日期:2017-11-11
  • Rare genetic diseases: update on diagnosis, treatment and online resources
    Drug. Discov. Today (IF 6.369) Pub Date : 2017-11-10
    Robert E. Pogue, Denise P. Cavalcanti, Shreya Shanker, Rosangela V. Andrade, Lana R. Aguiar, Juliana L.de Carvalho, Fabrício F. Costa

    Rare genetic diseases collectively impact a significant portion of the world’s population. For many diseases there is limited information available, and clinicians can find difficulty in differentiating between clinically similar conditions. This leads to problems in genetic counseling and patient treatment. The biomedical market is affected because pharmaceutical and biotechnology industries do not see advantages in addressing rare disease treatments, or because the cost of the treatments is too high. By contrast, technological advances including DNA sequencing and analysis, together with computer-aided tools and online resources, are allowing a more thorough understanding of rare disorders. Here, we discuss how a collection of various types of information together with the use of new technologies is facilitating diagnosis and, consequently, treatment of rare diseases.

    更新日期:2017-11-10
  • Recent advances in galactose-engineered nanocarriers for the site-specific delivery of siRNA and anticancer drugs
    Drug. Discov. Today (IF 6.369) Pub Date : 2017-11-10
    Ashay Jain, Atul Jain, Prahlad Parajuli, Vijay Mishra, Gargi Ghoshal, Bhupinder Singh, Uma Shankar Shivhare, Om Prakash Katare, Prashant Kesharwani

    Galactosylated nanocarriers have recently emerged as viable and versatile tools to deliver drugs at an optimal rate specifically to their target tissues or cells, thus maximizing their therapeutic benefits while circumventing off-target effects. The abundance of lectin receptors on cell surfaces makes the galactosylated carriers suitable for the targeted delivery of bioactives. Additionally, tethering of galactose (GAL) to various carriers, including micelles, liposomes, and nanoparticles (NPs), might also be appropriate for drug delivery. Here, we review recent advances in the development of galactosylated nanocarriers for active tumor targeting. We also provide a brief overview of the targeting mechanisms and cell receptor theory involved in the ligand–receptor-mediated delivery of drug carriers.

    更新日期:2017-11-10
  • Mesoporous silica nanoparticles: a smart nanosystem for management of breast cancer
    Drug. Discov. Today (IF 6.369) Pub Date : 2017-11-08
    Neelam Poonia, Viney Lather, Deepti Pandita

    Breast cancer is the second-leading cause of death in women worldwide owing to aggressive metastasis, lack of early diagnosis and poor access to treatment amenities. During the past decade, mesoporous silica nanoparticles (MSNs) have gained ground for the delivery of a wide variety of chemotherapeutic and bioimaging agents owing to their unique characteristics and straightforward fabrication methods. Present research studies based on MSNs have provided various potential insights in their applicability in breast cancer treatment by improving solubility and stability and decreasing the adverse effects of current treatment regimens. This review focuses on the applicability of this novel modality in the management of breast cancer.

    更新日期:2017-11-10
  • What is precise pathophysiology in development of hypertension in pregnancy? Precision medicine requires precise physiology and pathophysiology
    Drug. Discov. Today (IF 6.369) Pub Date : 2017-10-31
    Qinqin Gao, Jiaqi Tang, Na Li, Bailin Liu, Mengshu Zhang, Miao Sun, Zhice Xu

    It is widely accepted that placental ischemia is central in the evolution of hypertension in pregnancy. Many studies and reviews have targeted placental ischemia to explain mechanisms for initiating pregnancy hypertension. The placenta is rich in blood vessels, which are the basis for developing placental ischemia. However, is the physiology of placental vessels the same as that of nonplacental vessels? What is the pathophysiology of placental vessels in development of pregnancy hypertension? This review aims to provide a comprehensive summary of special features of placental vascular regulations and the pathophysiological changes linked to preeclamptic conditions. Interestingly, some popular theories or accepted concepts could be based on our limited knowledge and evidence regarding placental vascular physiology, pharmacology and pathophysiology. New views raised could offer interesting ideas for future investigation of mechanisms as well as targets for pregnancy hypertension.

    更新日期:2017-11-01
  • Interfering peptides targeting protein–protein interactions: the next generation of drugs?
    Drug. Discov. Today (IF 6.369) Pub Date : 2017-10-31
    Heriberto Bruzzoni-Giovanelli, Valerie Alezra, Nicolas Wolff, Chang-Zhi Dong, Pierre Tuffery, Angelita Rebollo

    Protein–protein interactions (PPIs) are well recognized as promising therapeutic targets. Consequently, interfering peptides (IPs) – natural or synthetic peptides capable of interfering with PPIs – are receiving increasing attention. Given their physicochemical characteristics, IPs seem better suited than small molecules to interfere with the large surfaces implicated in PPIs. Progress on peptide administration, stability, biodelivery and safety are also encouraging the interest in peptide drug development. The concept of an IP has been validated for several PPIs, generating great expectations for their therapeutic potential. Here, we describe approaches and methods useful for IP identification and in silico, physicochemical and biological-based strategies for their design and optimization. Selected promising in-vivo-validated examples are described and advantages, limitations and potential of IPs as therapeutic tools are discussed.

    更新日期:2017-11-01
  • Fishing anti(lymph)angiogenic drugs with zebrafish
    Drug. Discov. Today (IF 6.369) Pub Date : 2017-10-31
    Melissa García-Caballero, Ana R. Quesada, Miguel A. Medina, Manuel Marí-Beffa

    Zebrafish, an amenable small teleost fish with a complex mammal-like circulatory system, is being increasingly used for drug screening and toxicity studies. It combines the biological complexity of in vivo models with a higher-throughput screening capability compared with other available animal models. Externally growing, transparent embryos, displaying well-defined blood and lymphatic vessels, allow the inexpensive, rapid, and automatable evaluation of drug candidates that are able to inhibit neovascularisation. Here, we briefly review zebrafish as a model for the screening of anti(lymph)angiogenic drugs, with emphasis on the advantages and limitations of the different zebrafish-based in vivo assays.

    更新日期:2017-11-01
  • NCp7: targeting a multitasking protein for next-generation anti-HIV drug development: covalent inhibitors
    Drug. Discov. Today (IF 6.369) Pub Date : 2017-10-28
    Luca Sancineto, Nunzio Iraci, Oriana Tabarrini, Claudio Santi

    The major internal component of the HIV virion core is the nucleocapsid protein 7 (NCp7), a small, highly basic protein that is essential for multiple stages of the viral replicative cycle, and whose structure is preserved in all viral strains, including clinical isolates from therapy-experienced patients. This key protein is recognised as a potential target for an effective next-generation antiretroviral therapy, because it could offer the possibility to develop broad-spectrum agents that are less prone to select for resistant strains. Here, we provide a comprehensive overview of the covalent NCp7 inhibitors that have emerged over the past 25 years of drug discovery campaigns, emphasising, where possible, their structure–activity relationships (SARs) and pharmacophoric features.

    更新日期:2017-10-30
  • Current attempts to implement microRNA-based diagnostics and therapy in cardiovascular and metabolic disease: a promising future
    Drug. Discov. Today (IF 6.369) Pub Date : 2017-10-28
    Punniyakoti V. Thanikachalam, Srinivasan Ramamurthy, Zheng W. Wong, Koo B. Jin, Wong J. Ying, Mohd F.B. Abdullah, Chin Y. Haur, Chia C. Hou, Tan J. Yi, Neo W. Ting, Tan B. Sen, Khan W. Fang, Prashant Kesharwani

    MicroRNAs (miRNAs) are small, noncoding RNAs regulating gene expression at the post-translational level. miRNA-based therapeutic agents are important because of the functionality of miRNAs in regulating lipid and glucose metabolism and their role in the pathogenesis of metabolic disorders such as diabetes and obesity, where dysregulation leads to disease; they are also important in angiogenesis. miRNAs additionally serve as biomarkers in the diagnosis, prognosis and risk assessment of disease and in monitoring the response to treatment. Here, we provide a brief overview of progress in miRNA-based therapeutics in the preclinical and clinical setting and highlight the novel outcomes and opportunities in the diagnosis and treatment of metabolic conditions. In addition, we present the role of miRNAs in stem cell therapy which could have great potential in regenerative medicine.

    更新日期:2017-10-30
  • Alternative fluorophores designed for advanced molecular imaging
    Drug. Discov. Today (IF 6.369) Pub Date : 2017-10-27
    Lara G. Freidus, Priyamvada Pradeep, Pradeep Kumar, Yahya E. Choonara, Viness Pillay
    更新日期:2017-10-28
  • Anticancer activity of seaweeds
    Drug. Discov. Today (IF 6.369) Pub Date : 2017-10-26
    Anllely G. Gutiérrez-Rodríguez, Claudia Juárez-Portilla, Tatiana Olivares-Bañuelos, Rossana C. Zepeda

    Cancer is a major health problem worldwide and still lacks fully effective treatments. Therefore, alternative therapies, using natural products, have been proposed. Marine algae are an important component of the marine environment, with high biodiversity, and contain a huge number of functional compounds, including terpenes, polyphenols, phlorotannins, and polysaccharides, among others. These compounds have complex structures that have shown several biological activities, including anticancer activity, in several in vitro and in vivo models. Moreover, seaweed-derived compounds target important molecules that regulate cancer processes. Here, we review our current understanding of the anticancer activity of seaweeds.

    更新日期:2017-10-27
  • Indacaterol/glycopyrronium: a dual bronchodilator for COPD
    Drug. Discov. Today (IF 6.369) Pub Date : 2017-10-24
    Donald Banerji, Robert Fogel, Francesco Patalano

    Indacaterol/glycopyrronium (IND/GLY) 110/50 mg was the first once-daily, long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) fixed-dose combination (FDC) approved in Europe for the treatment of chronic obstructive pulmonary disease (COPD). Development of IND/GLY was driven by the need to improve the standard of care for patients with this disease, in terms of symptom control and exacerbation frequency. IGNITE, an adaptive, comprehensive, and innovative Phase 3 development program, demonstrated the efficacy of IND/glycopyrronium in optimising bronchodilation, reducing symptoms, and reducing exacerbations in patients with COPD. IGNITE challenged contemporary thinking about the pharmacological treatment and management of patients with this disease.

    更新日期:2017-10-25
  • 3D nerve cell cultures and complex physiological relevance
    Drug. Discov. Today (IF 6.369) Pub Date : 2017-10-23
    Xin Cheng, Kenneth Ndyabawe, Amish Asthana, William S. Kisaalita

    The field of tissue engineering has not yet provided knowledge on which a consensus for the complex physiological relevance (CPR) of neuronal cultures could be established. The CPR of 3D neuronal cultures can have a profound impact on the drug discovery process through the validation of in vitro models for the study of neuropsychiatric and degenerative diseases, as well as screening for neurotoxicity during drug development. Herein, we assemble evidence in support of the potential of [Ca2+]i oscillation frequency as a CPR outcome that can demonstrate the in vivo-like behavior of 3D cultures and differentiate them from 2D monolayers. We demonstrate that [Ca2+]i oscillation frequencies in 2D cultures are significantly higher than those found in 3D cultures, and provide a possible molecular explanation.

    更新日期:2017-10-24
  • Gemcitabine and glioblastoma: challenges and current perspectives
    Drug. Discov. Today (IF 6.369) Pub Date : 2017-10-23
    Chiara Bastiancich, Guillaume Bastiat, Frederic Lagarce

    Gemcitabine is a nucleoside analog currently used for the treatment of various solid tumors as a single agent or in combination with other chemotherapeutic drugs. Its use against highly aggressive brain tumors (glioblastoma) has been evaluated in preclinical and clinical trials leading to controversial results. Gemcitabine can inhibit DNA chain elongation, is a potent radiosensitizer and it can enhance antitumor immune activity, but it also presents some drawbacks (e.g., short half-life, side effects, chemoresistance). The aim of this review is to discuss the challenges related to the use of gemcitabine for glioblastoma and to report recent studies that suggest overcoming these obstacles opening new perspectives for its use in the field (e.g., gemcitabine derivatives and/or nanomedicines).

    更新日期:2017-10-24
  • Microarray patches: potentially useful delivery systems for long-acting nanosuspensions
    Drug. Discov. Today (IF 6.369) Pub Date : 2017-10-23
    Ryan F. Donnelly, Eneko Larrañeta

    Long-acting drug nanosuspension formulations are coming to the fore as controlled release strategies for several medical conditions and as a preventative measure against HIV infection. However, such delivery systems must, by necessity, be given by hypodermic injection, typically into muscle. This poses problems for patients who are needle-phobic, given that injections have to be administered on a weekly or monthly basis. Needle-stick injuries, inappropriate reuse of needles, and poor disposal practices are major challenges in developing countries. Dissolving microneedles (MNs) are capable of delivering high drug doses, if suitably designed and formulated, and are also capable of delivering nanoparticles (NPs) into viable skin. Given that such microneedles are minimally invasive and self-disabling, the potential for major enhancement in patient care and compliance exists. In this review, we explore the key considerations in the development of these combination drug delivery systems.

    更新日期:2017-10-24
  • Marketing authorisation of orphan medicines in Europe from 2000 to 2013
    Drug. Discov. Today (IF 6.369) Pub Date : 2017-10-23
    Matthias P. Hofer, Hanna Hedman, Maria Mavris, Franz Koenig, Thorsten Vetter, Martin Posch, Spiros Vamvakas, Jan Regnstrom, Stiina Aarum

    An analysis was performed on a data set of 157 orphan designated medicines with an outcome for marketing authorisation application (MAA) between 2000 and 2013. The intention was to understand the factors associated with marketing authorisation success, the challenges developers face regarding orphan medicine development, and how scientific advice (SA) is used during development. The results demonstrated that orphan medicines have a lower success rate compared with non-orphan medicines and that determinants for marketing authorisation success were company size and compliance with SA. Compliance with SA could help orphan medicine developers overcome clinical development challenges.

    更新日期:2017-10-24
  • Computational drug repositioning for rare diseases in the era of precision medicine
    Drug. Discov. Today (IF 6.369) Pub Date : 2017-10-18
    Brian Delavan, Ruth Roberts, Ruili Huang, Wenjun Bao, Weida Tong, Zhichao Liu

    There are tremendous unmet needs in drug development for rare diseases. Computational drug repositioning is a promising approach and has been successfully applied to the development of treatments for diseases. However, how to utilize this knowledge and effectively conduct and implement computational drug repositioning approaches for rare disease therapies is still an open issue. Here, we focus on the means of utilizing accumulated genomic data for accelerating and facilitating drug repositioning for rare diseases. First, we summarize the current genome landscape of rare diseases. Second, we propose several promising bioinformatics approaches and pipelines for computational drug repositioning for rare diseases. Finally, we discuss recent regulatory incentives and other enablers in rare disease drug development and outline the remaining challenges.

    更新日期:2017-10-18
  • Biochemical marker discovery, testing and evaluation for facilitating OA drug discovery and development
    Drug. Discov. Today (IF 6.369) Pub Date : 2017-10-14
    Anne-Christine Bay-Jensen, Christian S. Thudium, Oreste Gualillo, Ali Mobasheri
    更新日期:2017-10-14
  • Insights from pharmacological similarity of epigenetic targets in epipolypharmacology
    Drug. Discov. Today (IF 6.369) Pub Date : 2017-10-14
    J.Jesús Naveja, José L. Medina-Franco
    更新日期:2017-10-14
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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