2621928-55-8
2621928-55-8 structure
- Name: MRTX1133
- Chemical Name: MRTX1133
- CAS Number: 2621928-55-8
- Molecular Formula: C33H31F3N6O2
- Molecular Weight: 600.63
- Catalog: Signaling Pathways GPCR/G Protein Ras
- Create Date: 2021-12-20 07:50:03
- Modify Date: 2024-01-06 07:48:53
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MRTX1133 is a noncovalent, potent, and selective 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 KRASG12D of 0.2 pM. MRTX1133 prevents SOS1-catalyzed nucleotide exchange and/or formation of the KRASG12D/GTP/RAF1 complex, thereby inhibiting mutant KRAS-dependent signal transduction. MRTX1133 has picomolar binding affinity, single digit nanomolar activity in cellular assays, and marked in vivo efficacy in tumor models harboring KRASG12D mutations[1].
| Name | MRTX1133 |
|---|
| Description | MRTX1133 is a noncovalent, potent, and selective 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 KRASG12D of 0.2 pM. MRTX1133 prevents SOS1-catalyzed nucleotide exchange and/or formation of the KRASG12D/GTP/RAF1 complex, thereby inhibiting mutant KRAS-dependent signal transduction. MRTX1133 has picomolar binding affinity, single digit nanomolar activity in cellular assays, and marked in vivo efficacy in tumor models harboring KRASG12D mutations[1]. |
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| Related Catalog | |
| Target |
KRas G12D |
| In Vitro | MRTX1133 inhibits ERK phosphorylation in the AGS cell line with an IC50 ranging 1-10 nM (AsPC-1, Panc 04.03, Panc 02.03, SW1990, GP2D, Suit2, A427, SNU1033, and HPAC cells). In a 2D viability assay, the IC50 of MRTX1133 is 6 nM against AGS cells (KRAS G12D), while demonstrating more than 500-fold selectivity against MKN1, a cell line which is dependent on KRAS for its growth and survival due to the amplification of wild-type KRAS[1]. |
| In Vivo | MRTX1133 displays efficacious in a KRASG12D mutant xenograft mouse tumor model[1]. Animal Model: 6-8-weekold, female, athymic nude-Foxn1nu mice (Panc 04.03 model)[1] Dosage: 3, 10, or 30mg/kg Administration: Intraperitoneal; twice a day for 28 days Result: An antitumor efficacy study in this model resulted in MRTX1133 dose-dependent antitumor activity with 94% growth inhibition observed at 3 mg/kg BID (IP) and tumor regressions of −62% and −73% observed at 10 and 30 mg/kg BID (IP), respectively. |
| References |
[2]. KRAS G12D Inhibitor: MRTX1133. [(accessed on 22 April 2021)];2021 Available online. |
| Molecular Formula | C33H31F3N6O2 |
|---|---|
| Molecular Weight | 600.63 |
| Storage condition | -20°C |