Synonyms: 7-(1,3-Dimethyl-5-((4-(4-(methylsulfonyl)piperazin-1-yl)phenoxy)methyl)-1H-pyrazol-4-yl)-1-(2-morpholinoethyl)-3-(3-(naphthalen-1-yloxy)propyl)-1H-indole-2-carboxylic acid; 7-[5-[[4-[4-[(Dimethylamino)sulfonyl]-1-piperazinyl]phenoxy]methyl]-1,3-dimethyl-1H-pyrazol-4-yl]-1-[2-(4-morpholinyl)ethyl]-3-[3-(1-naphthalenyloxy)propyl]-1H-indole-2-carboxylic acid
Molecular Formula: C46H55N7O7S
Molecular Weight: 850.04
Linear Structural Formula: C46H55N7O7S
Purity: >=98% (HPLC)
Storage: -20C
Biochem Physiol Actions: A-1210477 is a BH3 mimetic that targets MCL-1 with high affinity (Ki = 0.43 nM) and selectivity (Ki >0.66 muM for BCL-2, BCL-XL, BCL-W, and A1), exhibiting little to no activity toward panels of 80 kinases (IC50 >8.5 muM) and 21 GPCRs (IC50 & EC50 >10 muM). A-1210477 selectively inhibits the survival of MCL-1-dependent (IC50 ~4 muM/multiple myeloma H929, 5.3 muM/NSCLC H2110, 7.2 muM/NSCLC H23), but not BCL-2-dependent RS4;11, cultures via apoptosis induction and potentiates BCL-2/BCL-XL inhibitor ABT-263 (Navitoclax) killing in a variety of cancer cell cultures where ABT-263 alone is ineffective. A-1210477 is also shown to cause cellular MCL-1 upregulation, most likely due to blocking MCL-1 interaction with BH3-only proteins such as NOXA and MULE known to mediate MCL-1 ubiquitylation for proteasomal degradation.