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Recent Patents on Anti-Cancer Drug Discovery

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ISSN (Print): 1574-8928
ISSN (Online): 2212-3970

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Santacruzamate A Compositions, Analogs and Methods of Use: A Patent Evaluation of WO 2014/018913 (A2)

Author(s): Lin Zhang and Lei Zhang*

Volume 16, Issue 4, 2021

Published on: 15 June, 2021

Page: [469 - 478] Pages: 10

DOI: 10.2174/1872212115666210615153507

Price: $65

Abstract

Background: Santacruzamate A (SCA) is a natural product isolated from a marine cyanobacterium. Activity test results revealed that SCA is a highly potent HDAC2 inhibitor with an IC50 value of 0.112 nM. The IC50 of SCA in inhibiting cancer cell proliferation is 28.3 μM and 1.3μM on HCT116 and HuT-78 cells, respectively.

Objective: To develop HDAC inhibitors with improved activity, SCA analogs were synthesized for the Structure-Activity Relationship (SAR) studies.

Methods: Various substituted groups were introduced into the zinc binging group, linker, and cap regions of SCA by various chemical synthetic methods.

Results: Compared with SCA, the derivatives of SCA did not exhibit improved HDAC2 inhibitory activity. Nevertheless, several molecules such as III-32, III-33, IV-4b, and IV-11 showed improved activity in inhibiting cell proliferation on HCT116 and HuT-78 cells.

Conclusion: Collectively, a potent HDAC2 inhibitor SCA was discovered as a lead compound for further development of selective HDAC inhibitors.

Keywords: Cancer, histone deacetylase 2, inhibitor, santacruzamate A, structure-activity relationship, selectivity.

« Previous Next »
[1]
Bernstein BE, Tong JK, Schreiber SL. Genomewide studies of histone deacetylase function in yeast. Proc Natl Acad Sci USA 2000; 97(25): 13708-13.
[http://dx.doi.org/10.1073/pnas.250477697] [PMID: 11095743]
[2]
de Ruijter AJ, van Gennip AH, Caron HN, Kemp S, van Kuilenburg AB. Histone deacetylases (HDACs): Characterization of the classical HDAC family. Biochem J 2003; 370(Pt 3): 737-49.
[http://dx.doi.org/10.1042/bj20021321] [PMID: 12429021]
[3]
Foglietti C, Filocamo G, Cundari E, et al. Dissecting the biological functions of Drosophila histone deacetylases by RNA interference and transcriptional profiling. J Biol Chem 2006; 281(26): 17968-76.
[http://dx.doi.org/10.1074/jbc.M511945200] [PMID: 16632473]
[4]
Zhang L, Han Y, Jiang Q, et al. Trend of histone deacetylase inhibitors in cancer therapy: Isoform selectivity or multitargeted strategy. Med Res Rev 2015; 35(1): 63-84.
[http://dx.doi.org/10.1002/med.21320] [PMID: 24782318]
[5]
Marks PA. Discovery and development of SAHA as an anticancer agent. Oncogene 2007; 26(9): 1351-6.
[http://dx.doi.org/10.1038/sj.onc.1210204] [PMID: 17322921]
[6]
Grant C, Rahman F, Piekarz R, et al. Romidepsin: A new therapy for cutaneous T-cell lymphoma and a potential therapy for solid tumors. Expert Rev Anticancer Ther 2010; 10(7): 997-1008.
[http://dx.doi.org/10.1586/era.10.88] [PMID: 20645688]
[7]
Rashidi A, Cashen AF. Belinostat for the treatment of relapsed or refractory peripheral T-cell lymphoma. Future Oncol 2015; 11(11): 1659-64.
[http://dx.doi.org/10.2217/fon.15.62] [PMID: 26043217]
[8]
Greig SL. Panobinostat: A review in relapsed or refractory multiple myeloma. Target Oncol 2016; 11(1): 107-14.
[http://dx.doi.org/10.1007/s11523-015-0413-6] [PMID: 26826025]
[9]
Krämer OH. HDAC2: A critical factor in health and disease. Trends Pharmacol Sci 2009; 30(12): 647-55.
[http://dx.doi.org/10.1016/j.tips.2009.09.007] [PMID: 19892411]
[10]
Müller BM, Jana L, Kasajima A, et al. Differential expression of histone deacetylases HDAC1, 2 and 3 in human breast cancer-overexpression of HDAC2 and HDAC3 is associated with clinicopathological indicators of disease progression. BMC Cancer 2013; 13: 215.
[http://dx.doi.org/10.1186/1471-2407-13-215] [PMID: 23627572]
[11]
Shan W, Jiang Y, Yu H, et al. HDAC2 overexpression correlates with aggressive clinicopathological features and DNA-damage response pathway of breast cancer. Am J Cancer Res 2017; 7(5): 1213-26.
[PMID: 28560068]
[12]
Pavlik CM, Wong CY, Ononye S, et al. Santacruzamate A, a potent and selective histone deacetylase inhibitor from the Panamanian marine cyanobacterium cf. Symploca sp. J Nat Prod 2013; 76(11): 2026-33.
[http://dx.doi.org/10.1021/np400198r] [PMID: 24164245]
[13]
Gromek SM, deMayo JA, Maxwell AT, et al. Synthesis and biological evaluation of santacruzamate A analogues for anti-proliferative and immunomodulatory activity. Bioorg Med Chem 2016; 24(21): 5183-96.
[http://dx.doi.org/10.1016/j.bmc.2016.08.040] [PMID: 27614919]
[14]
O'hagan R, Phillips J, Pinheiro EM, Sriram V. Combination of a PD-1 antagonist and vorinostat for treating cancer. WO2016153839, 2016.
[15]
Ge M, Li D, Liu H, Qiao Z, Sun Y. Application of combination of bortezomib and panobinostat or vorinostat in preparing drugs for treating drug-resistant MLL. CN110314222, 2019.
[16]
Huang W, Xu S, Yan D, Zhou Y, Zhu X. Preparation and application of amphiphilic drug-drug nanoparticle for reversing platinum-based anticancer drug resistance in cancer therapy. WO2018133687, 2018.
[17]
Tao A, Yan X, Yuan J. Romidepsin fat microsphere preparation and preparing method thereof. CN106137980, 2016.
[18]
Blodgett J, Oddone G, Reveles R. A method for increasing romidepsin production from fermentation broth. WO2020139453, 2020.
[19]
Dhiman AM, Sharma TP, Vaid AS. Process for isolation of romidepsin from fermentation broth and preparation of crystals of romidepsin. US10294276, 2019.
[20]
Bloom C, Lemarchand C, Pivette P, Yates I. WO2019002614, 2019.
[21]
Acharya H, Cabri W, Lahiri S, et al. Polymorphic forms of belinostat and processes for preparation thereof. WO2018020406, 2018.
[22]
Bloom C, Lemarchand C, Pivette P, Yates I. New oral formulations of belinostat. AU2018294561, 2020.
[23]
Chiluvuru P, Dakarapu VV, Dangudubiyyam CS, Prashant P, Rampalli S, Upalla LK. Amorphous panobinostat and its lactate salt. WO2018163114, 2018.
[24]
Buddh M, Joshi A, Parikh C, et al. Novel salts and polymorphic forms of panobinostat. WO2017221163, 2017.
[25]
Binlich F, Capdeville R, Grazioli L, Lin R, Mu S, Paul S. Panobinostat dosages for multiple myeloma. US2018028497, 2018.
[26]
Dziedzic R, Kennedy P, Logan J, Saebi A, Spokoyny A. Carborane-based Histone Deacetylase (HDAC) inhibitors. WO2020117976, 2020.
[27]
Ghosh S, Guerriero J, Kruidenier L, et al. Methods of use of a class LLA HDAC inhibitor. WO2017112838, 2017.
[28]
Erichsen KD, Jeffers M, Lichenstein H, Qian X, Ritchie J, Sehested M. Combination therapies using HDAC inhibitors. US10799469, 2020.
[29]
Baylin SB, Stone M, Topper M, Zahnow C. Compositions and methods for treating solid tumors. WO2017035453, 2017.
[30]
Balunas MJ, Pavlik CM, Gerwick WH. Santacruzamate a compositions and analogs and methods of use. WO2014018913, 2014.
[31]
Chokhawala H, Gutierrez JA, Kuchenreuther J, Tai YS. Production of chemicals from renewable sources. WO2020220001, 2020.
[32]
Zhao G. Estradiol culture medium dedicated to culture of mesenchymal stem cells and application thereof. CN109022357, 2018.
[33]
Chou A, Gonzalez R. Bioconversion of 1-carbon feedstocks to chemicals and fuels. WO2017210381, 2017.
[34]
Chou A, Clomburg J, Gonzalez R. Biosynthesis of products from 1-carbon compounds. WO2016069929, 2016.

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