MCL-1 as a potent target for cancer: Recent advancements, structural insights and SAR studies

被引:2
作者
Sharma, Vishakha [1 ]
Kumar, Ankush [1 ]
机构
[1] Amity Univ Punjab, Amity Sch Pharmaceut Sci, Mohali, India
关键词
Mcl-1; Docking; Apoptosis; Inhibitors; SAR; BCL-2 FAMILY PROTEINS; CELL-SURVIVAL; APOPTOSIS; MITOCHONDRIA; EXPRESSION; PATHWAY; INHIBITOR; DISCOVERY; AUTOPHAGY; DOMAIN;
D O I
10.1016/j.bioorg.2025.108211
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The myeloid cell leukemia-1 (Mcl-1) differentiation protein belongs to the B-cell lymphoma 2 (Bcl-2) family of proteins which regulates the apoptosis or cell death. Mcl-1 is known for its pro-survival in response to various stressors. Therefore, it acts as a prominent target in cancer treatment. Mcl-1 has emerged as one of the validated drug targets for anticancer drug discovery as their expression has been implicated in the pathogenesis of cancers. In this review, we have included the various inhibitors based on many heterocyclic rings such as pyrrole, pyrazole, coumarin, quinoline and indole. This manuscript incorporates the anticancer activity, structure activity relationship (SAR) and molecular modelling of recently synthesized Mcl-1 inhibitors. The clinical trial status of Mcl-1 inhibitors is also described. But till now, no Mcl-1 inhibitor has been approved by any drug authority. This review is based on extensive research in the field of designing Mcl-1 inhibitors from 2020 to till now. It will provide extensive information to researchers and scientists for designing of novel Mcl-1 inhibitors.
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页数:13
相关论文
共 72 条
[1]   Mcl-1 is a potential therapeutic target in multiple types of cancer [J].
Akgul, C. .
CELLULAR AND MOLECULAR LIFE SCIENCES, 2009, 66 (08) :1326-1336
[2]  
Alzain A.A., 2023, J. Biomol. Struct. Dyn., P1
[3]   The antiapoptotic member of the Bcl-2 family Mcl-1 is a CTL target in cancer patients [J].
Andersen, MH ;
Becker, JC ;
Straten, PT .
LEUKEMIA, 2005, 19 (03) :484-485
[4]   The landscape of somatic copy-number alteration across human cancers [J].
Beroukhim, Rameen ;
Mermel, Craig H. ;
Porter, Dale ;
Wei, Guo ;
Raychaudhuri, Soumya ;
Donovan, Jerry ;
Barretina, Jordi ;
Boehm, Jesse S. ;
Dobson, Jennifer ;
Urashima, Mitsuyoshi ;
Mc Henry, Kevin T. ;
Pinchback, Reid M. ;
Ligon, Azra H. ;
Cho, Yoon-Jae ;
Haery, Leila ;
Greulich, Heidi ;
Reich, Michael ;
Winckler, Wendy ;
Lawrence, Michael S. ;
Weir, Barbara A. ;
Tanaka, Kumiko E. ;
Chiang, Derek Y. ;
Bass, Adam J. ;
Loo, Alice ;
Hoffman, Carter ;
Prensner, John ;
Liefeld, Ted ;
Gao, Qing ;
Yecies, Derek ;
Signoretti, Sabina ;
Maher, Elizabeth ;
Kaye, Frederic J. ;
Sasaki, Hidefumi ;
Tepper, Joel E. ;
Fletcher, Jonathan A. ;
Tabernero, Josep ;
Baselga, Jose ;
Tsao, Ming-Sound ;
Demichelis, Francesca ;
Rubin, Mark A. ;
Janne, Pasi A. ;
Daly, Mark J. ;
Nucera, Carmelo ;
Levine, Ross L. ;
Ebert, Benjamin L. ;
Gabriel, Stacey ;
Rustgi, Anil K. ;
Antonescu, Cristina R. ;
Ladanyi, Marc ;
Letai, Anthony .
NATURE, 2010, 463 (7283) :899-905
[5]   Exon skipping in Mcl-1 results in a Bcl-2 homology domain 3 only gene product that promotes cell death [J].
Bingle, CD ;
Craig, RW ;
Swales, BM ;
Singleton, V ;
Zhou, P ;
Whyte, MKB .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (29) :22136-22146
[6]   Epidermal growth factor regulates Mcl-1 expression through the MAPK-Elk-1 signalling pathway contributing to cell survival in breast cancer [J].
Booy, E. P. ;
Henson, E. S. ;
Gibson, S. B. .
ONCOGENE, 2011, 30 (20) :2367-2378
[7]   Regulation of apoptosis by Bcl-2 family proteins [J].
Burlacu, A .
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2003, 7 (03) :249-257
[8]   BCL-X(L) AND BCL-2 REPRESS A COMMON PATHWAY OF CELL-DEATH [J].
CHAO, DT ;
LINETTE, GP ;
BOISE, LH ;
WHITE, LS ;
THOMPSON, CB ;
KORSMEYER, SJ .
JOURNAL OF EXPERIMENTAL MEDICINE, 1995, 182 (03) :821-828
[9]   A natural chalcone induces apoptosis in lung cancer cells: 3D-QSAR, docking and an in vivo/vitro assay [J].
Chen, Gang ;
Zhou, Di ;
Li, Xue-Zheng ;
Jiang, Zhe ;
Tan, Chengyu ;
Wei, Xiu-Yan ;
Ling, Junhong ;
Jing, Jing ;
Liu, Fen ;
Li, Ning .
SCIENTIFIC REPORTS, 2017, 7
[10]   Tetrazole and acylsulfonamide bioisosteric replacements of the carboxylic acid in a dual MCL-1/BCL-xL inhibitor are tolerated [J].
Chen, Lijia ;
Lowe, Brandon ;
Fletcher, Steven .
RSC ADVANCES, 2023, 13 (49) :34322-34334