MRTX-1257

MRTX-1257 is a potent, selective, irreversible, covalent and orally active inhibitor of KRAS G12C with IC50 of 900 pM for KRAS dependent ERK phosphorylation in H358 cells.

Product information

CAS Number: 2206736-04-9

Molecular Weight: 565.71

Formula: C33H39N7O2

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

Smiles: CN1CCC[C@H]1COC1N=C(C2CCN(CC=2N=1)C1=CC=CC2=CC=CC(C)=C21)N1C[C@H](CC#N)N(CC1)C(=O)C=C

InChiKey: YRYQLVCTQFBRLD-UIOOFZCWSA-N

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

Technical Data

Appearance: Solid Power

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

Solubility: DMSO 100 mg/mL (176.77 mM) Ethanol 30 mg/mL (53.03 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: ≥12 months 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:

MRTX1257 demonstrates rapid, irreversible modification of GDP-bound recombinant KRAS G12C and suppresses ERK phosphorylation with an IC50 = 1 nM in the H358 cell line. In proteomics studies designed to assess global protein modification, MRTX1257 is shown to be highly selective for the targeted Cys12 of KRAS G12C versus other surface-exposed cysteine residues in NCI-H358 cells.

In Vivo:

MRTX1257 exhibits 31% bioavailability in mouse, demonstrates near-complete inhibition of KRAS signaling in tumor tissue, and complete durable tumor regression in MIA PaCa-2 xenografts.

References:

1. Matthew A. Marx, et al. MIRATI THERAPLUTICS.
2. Matthew A. Marx, et al. Mol Cancer Res 2020;18(5_Suppl):Abstr

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