Adagrasib

Adagrasib (MRTX849) is a potent, selective, and covalent KRASG12C inhibitor that exhibits favorable drug-like properties, selectively modifies mutant cysteine 12 in GDP-bound KRASG12C and inhibits KRAS-dependent signaling.

Product information

CAS Number: 2326521-71-3

Molecular Weight: 604.12

Formula: C32H35ClFN7O2

Synonym:

MRTX849

Chemical Name: 2-((S)-4-(7-(8-chloronaphthalen-1-yl)-2-(((S)-1-methylpyrrolidin-2-yl)methoxy)-5, 6, 7, 8-tetrahydropyrido[3, 4-d]pyrimidin-4-yl)-1-(2-fluoroacryloyl)piperazin-2-yl)acetonitrile

Smiles: CN1CCC[C@H]1COC1=NC2CN(CCC=2C(=N1)N1C[C@H](CC#N)N(CC1)C(=O)C(=C)F)C1=CC=CC2=CC=CC(Cl)=C21

InChiKey: PEMUGDMSUDYLHU-ZEQRLZLVSA-N

InChi: InChI=1S/C32H35ClFN7O2/c1-21(34)31(42)41-17-16-40(18-23(41)11-13-35)30-25-12-15-39(28-10-4-7-22-6-3-9-26(33)29(22)28)19-27(25)36-32(37-30)43-20-24-8-5-14-38(24)2/h3-4,6-7,9-10,23-24H,1,5,8,11-12,14-20H2,2H3/t23-,24-/m0/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO：100 mg/mL (165.53 mM)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

To evaluate the breadth of MRTX849 activity, its effect on cell viability is determined across a panel of 17 KRASG12C-mutant and three non-KRASG12C-mutant cancer cell lines using 2D (3-day, adherent cells) and 3D (12-day, spheroids) cell growth conditions. MRTX849 potently inhibits cell growth in the vast majority of KRASG12C-mutant cell lines with IC50 values ranging between 10 nM and 973 nM in the 2D format and between 0.2 nM and 1042 nM in the 3D format..

In Vivo:

Rapid tumor regression is observed at the earliest posttreatment tumor measurement and animals in the 30 mg/kg and 100 mg/kg cohorts exhibits evidence of a complete response at study Day 15. Dosing is stopped at study Day 16 and all 4 mice in the 100 mg/kg cohort and 2 out of 7 mice in the 30 mg/kg cohort remains tumor-free through study Day 70.

References:

1. Kyriakos P. Papadopoulos, et al. A phase I/II multiple expansion cohort trial of MRTX849 in patients with advanced solid tumors with KRAS G12C mutation. Journal of Clinical Oncology 2019 37:15_suppl, TPS3161-TPS3161.
2. Christensen JG, et al. The KRASG12C Inhibitor, MRTX849, Provides Insight Toward Therapeutic Susceptibility of KRAS Mutant Cancers in Mouse Models and Patients. Cancer Discov. 2019 Oct 28. pii: CD-19-1167.

Products are for research use only. Not for human use.