MRTX-1257

• CAT Number: I019328
• CAS Number: 2206736-04-9
• Molecular Formula: C33H39N7O2
• Molecular Weight: 565.71
• Purity: ≥95%
• Synonyms: 2-[(2S)-4-[7-(8-methylnaphthalen-1-yl)-2-[[(2S)-1-methylpyrrolidin-2-yl]methoxy]-6,8-dihydro-5H-pyrido[3,4-d]pyrimidin-4-yl]-1-prop-2-enoylpiperazin-2-yl]acetonitrile
• InChI: InChI=1S/C33H39N7O2/c1-4-30(41)40-19-18-39(20-25(40)13-15-34)32-27-14-17-38(29-12-6-10-24-9-5-8-23(2)31(24)29)21-28(27)35-33(36-32)42-22-26-11-7-16-37(26)3/h4-6,8-10,12,25-26H,1,7,11,13-14,16-22H2,2-3H3/t25-,26-/m0/s1
• InChIKey: YRYQLVCTQFBRLD-UIOOFZCWSA-N
• SMILES: CC1=C2C(=CC=C1)C=CC=C2N3CCC4=C(C3)N=C(N=C4N5CCN(C(C5)CC#N)C(=O)C=C)OCC6CCCN6C

MRTX-1257 is a selective, irreversible, covalent and orally active KRAS G12C inhibitor, with an IC50 of 900 pM for KRAS dependent ERK phosphorylation in H358 cells[1].
MRTX-1257 (1 mg/kg, 3 mg/kg, 10 mg/kg, 30 mg/kg and 100 mg/kg, orally, daily for 30 days) shows rapid tumor growth inhibition at all dose groups in MIA PaCa-2 G12C Xenograft model in mice[1].?
MRTX-1257 shows sustained regression at 3,10, 30, and 100 mg/kg dose groups[1].?
MRTX-1257 dosed of 100 mg/kg daily leads to complete responses that are maintained >70 days after cessation of treatment[1].

Reference

[1]. Matthew et al. Structure-Based Drug Discovery of MRTX1257, a Selective, Covalent KRAS G12C Inhibitor with Oral Activity in Animal Models of Cancer.