Abstract
Inflammation is not only a defense mechanism of the innate immune system against invaders, but it is also involved in the pathogenesis of many diseases such as atherosclerosis, thrombosis, diabetes, epilepsy, and many neurodegenerative disorders. The World Health Organization (WHO) reports worldwide estimates of people (9.6% in males and 18.0% in females) aged over 60 years, suffering from symptomatic osteoarthritis, and around 339 million suffering from asthma. Other chronic inflammatory diseases, such as ulcerative colitis and Crohn’s disease are also highly prevalent. The existing anti-inflammatory agents, both non-steroidal and steroidal, are highly effective; however, their prolonged use is marred by the severity of associated side effects. A holistic approach to ensure patient compliance requires understanding the pathophysiology of inflammation and exploring new targets for drug development. In this regard, various intracellular cell signaling pathways and their signaling molecules have been identified to be associated with inflammation. Therefore, chemical inhibitors of these pathways may be potential candidates for novel anti-inflammatory drug approaches. This review focuses on the anti-inflammatory effect of these inhibitors (for JAK/STAT, MAPK, and mTOR pathways) describing their mechanism of action through literature search, current patents, and molecules under clinical trials.
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Abbreviations
- PG:
-
Prostaglandin
- T-cells:
-
Thymus cells
- B-cells:
-
Bone marrow cells
- WBCs:
-
White blood cells
- WHO:
-
World health organization
- NSAIDs:
-
Non-steroidal anti-inflammatory drugs
- COX:
-
Cyclooxygenase
- JAK/STAT:
-
Janus kinases and signal transducer and activator of transcription proteins
- MAPK:
-
Mitogen-activated protein kinase
- mTOR:
-
Mammalian target of rapamycin
- JAK:
-
Janus kinases
- MEK:
-
Serine/tyrosine/threonine kinase
- mTOR:
-
Mammalian target of rapamycin
- ER-positive breast cancer:
-
Estrogen receptor-positive breast cancer
- RA:
-
Rheumatoid arthritis
- cAMP:
-
Cyclic adenosine monophosphate
- cGMP:
-
Cyclic guanosine monophosphate
- Ca2+ :
-
Calcium
- NF-κB:
-
Nuclear factor kappa light chain enhancer of activated B cells
- DNA:
-
Deoxyribonucleic acid
- SH2:
-
Src homology 2
- EGF:
-
Epidermal growth factor
- IL:
-
Interleukin
- IFN:
-
Interferon
- LIF:
-
Leukemia inhibitory factor
- CNTF:
-
Ciliary neurotrophic factor
- OM:
-
Oncostatin M
- CT-1:
-
Cardiotrophin-1
- G-CSF:
-
Granulocyte colony-stimulating factor
- GM-CSF:
-
Granulocyte–macrophage colony stimulating factor
- GH:
-
Growth factor
- Epo:
-
Erythropoietin
- Th2:
-
Thymus helper-2
- IBD:
-
Inflammatory bowel disease
- JNK:
-
C-Jun N-terminal kinase
- ERK:
-
Xtracellular-signal-regulated kinase
- MAPKKK:
-
Mitogen-activated protein kinase kinase kinase
- MAPKK:
-
Mitogen-activated protein kinase kinase
- MAPK:
-
Mitogen-activated protein kinase
- RTK:
-
Receptor tyrosine kinases
- GPCR:
-
G-protein-coupled receptors
- TYK-2:
-
Non-receptor tyrosine-protein kinase
- Sap-1a:
-
Serum response factor accessory protein-1
- GADD153:
-
Growth arrest- and DNA damage-inducible gene 153
- MNK1:
-
MAPK interacting protein kinase 1
- ASK:
-
Apoptosis signal-regulating kinase
- VEGF:
-
Vascular endothelial growth factor
- BMK1:
-
Big mitogen-activated protein kinase
- Atf-2:
-
Activating transcription factor 2
- PEG-2:
-
Prostaglandin E2
- TPA:
-
Tissue plasminogen activator
- LPS:
-
Lipopolysaccharide
- PPR:
-
Pattern recognition receptor
- CSBP:
-
Cytokine-specific binding protein
- Cd42:
-
Glycoprotein Ib
- TSC:
-
Tissue sclerosis complex
- OA:
-
Osteoarthritis
- mRNA:
-
Messenger ribonucleic acid
- COPD:
-
Chronic obstructive pulmonary disorder
- PI3K:
-
Phosphoinositide 3-kinase
- TNF:
-
Tumor necrosis factor
- NA:
-
Not available
- CD:
-
Crohn’s disease
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Nailwal, N.P., Doshi, G.M. Role of intracellular signaling pathways and their inhibitors in the treatment of inflammation. Inflammopharmacol 29, 617–640 (2021). https://doi.org/10.1007/s10787-021-00813-y
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DOI: https://doi.org/10.1007/s10787-021-00813-y