To further explore MCL1 biology in MM, we use a clinical-grade small-molecule MCL1 inhibitor, AZD5991, to investigate the mechanistic underpinning of MCL1 inhibition in MM. AZD5991 is a potent and selective macrocyclic inhibitor of MCL1 [9] that is currently in phase I clinical trial in ...
95. Subsequently, AMG 176, a first-in-class orally bioavailable inhibitor of MCL1, was reported96. AMG 176 has two primary advantages over S63845: it can be administered orally and is effective against B cell, monocytic, and neutrophilic leukemia. Soon after the development of AMG 176, anothe...
Here, we describe the in vitro and in vivo activity of GS-9716, a potent and selective MCL1 small molecule inhibitor that binds directly to MCL1 and induces rapid apoptosis in cancer cells by activating the mitochondrial apoptotic pathway. GS-9716 displayed potent and selective disruption of ...
Because addition of the BCL2 inhibitor venetoclax resulted in compensatory upregulation of MCL1, we established a three-drug combination composed of sirolimus, venetoclax, and the MCL1 inhibitor S63845. This well-tolerated drug combination potently and synergistically induces apoptosis in both zebrafish ...
Importantly, MCL1 has been implicated in mediating resistance to chemotherapy as well as targeted therapies, including the BCL2 inhibitor, venetoclax. Here, we describe the in vitro and in vivo activity of PRT1419, a potent and selective inhibitor of human MCL1, that can induce tumor cell ...
CDK7 has become a potential therapeutic target, and CDK7 inhibitors have entered the clinical trial as promising methods for a variety of malignancies. THZ1 is a covalent inhibitor of CDK7, which shows strong antitumor effects in various cancers by inhibition of CDK79,10,11,12,13,14,15,16....
3e). Moreover, the broad-spectrum caspase inhibitor Q-VD-OPh inhibited the cell death induced by the anticancer drugs (Supplementary Fig. 3f). Sensitivities to these agents varied widely among the ovarian cancer cell lines. Fig. 2: Preformed BAK/MCL1 complexes predict cancer cell sensitivity to...