MRTX1133

MRTX1133 is a noncovalent, potent, and selective alkyne-based KRAS G12D inhibitor. MRTX1133 optimally fills the switch II pocket and extends three substituents to favorably interact with the protein, resulting in an estimated KD against KRAS G12D of 0.2 pM. MRTX1133 prevents SOS1-catalyzed nucleotide exchange and/or formation of the KRAS G12D/GTP/RAF1 complex, thereby inhibiting mutant KRAS-dependent signal transduction. MRTX1133 selectively inhibits KRAS G12D mutant, but not KRAS wild-type, tumor cells. MRTX1133 has single digit nanomolar activity in cellular assays and marked in vivo efficacy in tumor models harboring KRAS G12D mutations[1][2].

Product Specifications

CAS Number

[2621928-55-8]

UNSPSC

12352005

Hazard Statement

H302, H315, H319, H335

Target

Ras

Type

Reference compound

Related Pathways

GPCR/G Protein; MAPK/ERK Pathway

Field of Research

Cancer

Assay Protocol

https://www.medchemexpress.com/mrtx1133.html

Purity

99.97

Solubility

DMSO : 50 mg/mL (ultrasonic)

Smiles

OC1=CC(C2=C(F)C3=NC(OC[C@]45C[C@@H](F)CN4CCC5)=NC(N6C[C@H]7N[C@H](CC7)C6)=C3C=N2)=C8C(C#C)=C(F)C=CC8=C1

Molecular Formula

C33H31F3N6O2

Molecular Weight

600.63

Precautions

H302, H315, H319, H335

References & Citations

[1]Wang X, et al. Identification of MRTX1133, a Noncovalent, Potent, and Selective KRAS G12D Inhibitor [published online ahead of print, 2021 Dec 10]. J Med Chem. 2021;10.1021/acs.jmedchem.1c01688.