Drennen, Brandon published the artcileScaffold hopping from indoles to indazoles yields dual MCL-1/BCL-2 inhibitors from MCL-1 selective leads, Product Details of C9H8N2O2, the main research area is indole indazole MCL1 BCL2 inhibitor scaffold hopping.
Overexpression of the anti-apoptotic BCL-2 proteins is associated with the development and progression of a range of cancers. Venetoclax, an FDA-approved BCL-2 inhibitor, is fast becoming the standard-of-care for acute myeloid leukemia and chronic lymphocytic leukemia. However, the median survival offered by venetoclax is only 18 mo (as part of a combination therapy regimen), and one of the primary culprits for this is the concomitant upregulation of sister anti-apoptotic proteins, in particular MCL-1 (and BCL-xL), which provides an escape route that manifests as venetoclax resistance. Since inhibition of BCL-xL leads to thrombocytopenia, we believe that a dual MCL-1/BCL-2 inhibitor may provide an enhanced therapeutic effect relative to a selective BCL-2 inhibitor. Beginning with a carboxylic acid-containing literature compound that is a potent inhibitor of MCL-1 and a moderate inhibitor of BCL-2, we herein describe our efforts to develop dual inhibitors of MCL-1 and BCL-2 by scaffold hopping from an indole core to an indazole framework. Subsequently, further elaboration of our novel N2-substituted, indazole-3-carboxylic acid lead into a family of indazole-3-acylsulfonamides resulted in improved inhibition of both MCL-1 and BCL-2, possibly through occupation of the p4 pocket, with minimal or no inhibition of BCL-xL.
RSC Medicinal Chemistry published new progress about Animal gene, Bcl-2 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 5805-53-8 belongs to class imidazoles-derivatives, name is Methyl 1H-benzo[d]imidazole-2-carboxylate, and the molecular formula is C9H8N2O2, Product Details of C9H8N2O2.
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem