Shelf life (days): 1460.0
Formulation: A solid
Formal Name: (1S,2S)-N-[(2R,14S,18S)-1-ethyl-18,19,20,21-tetrahydro-2-[2-[(1S)-1-methoxyethyl]-5-(4-methyl-1-piperazinyl)-3-pyridinyl]-25,25-dimethyl-15,22-dioxo-17H-5,3-([4,2]-endo-thiazolopropano[1,3]-endo-pyridazinomethanoxypropano)-1H-indol-14-yl]-2-methyl-cyclopropanecarboxamide
Purity: ≥98%
Formula Markup: C44H58N8O5S
Formula Weight: 811.1
CAS Number: 2765081-21-6
Notes: RMC-6236 is a non-covalent inhibitor of GTP-bound RAS.{51889} It binds to peptidyl-prolyl cis-trans isomerase A (PPIase A), also known as cyclophilin A (CypA; Kd = 55.3 nM) to form a binary complex that then binds to wild-type K-Ras, K-Ras(G12V), and K-Ras(G12D) (Kds = 131, 364, and 154 nM, respectively). RMC-6236 forms a trimeric complex with PPIase A and a K-Ras, H-Ras, N-Ras, or mutant Ras variant and disrupts the protein-protein interaction between these Ras variants and the B-RAF Ras-binding domain (IC50s = 28-220 nM). It induces apoptosis in 28 K-Ras(G12X) and five N-Ras(Q61X) mutant cancer cell lines when used at concentrations ranging from 1 to 100 nM. In vivo, RMC-6236 (25 mg/kg) inhibits intratumoral ERK phosphorylation and reduces tumor volume in Capan-2 and NCI H441 pancreatic ductal adenocarcinoma (PDAC) mouse xenograft models. It also reduces tumor growth in 29 non-small cell lung cancer (NSCLC), 22 PDAC, and 23 colorectal cancer K-Ras(G12X) mutant mouse xenograft models when administered at a dose of 25 mg/kg.
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