MRTX1133

SKU: orb1298201

Description

MRTX1133 is a potent, selective, and non-covalent small-molecule inhibitor targeting the KRAS G12D mutant with sub-picomolar affinity (K_D = 0.2 pM). It demonstrates antitumor efficacy in G12D-mutated cell lines and in vivo models, showing selectivity over wild-type KRAS, making it a valuable research tool for oncology and targeted therapy studies.

Research Area

Pharmacology & Drug Discovery, Signal Transduction

Key Properties

• CAS Number: 2621928-55-8
• MW: 600.63
• Purity: 99.60%
• Formula: C₃₃H₃₁F₃N₆O₂
• SMILES: Oc1cc(-c2ncc3c(nc(OC[C@@]45CCCN4C[C@H](F)C5)nc3c2F)N2C[C@@H]3CC[C@H](C2)N3)c2c(C#C)c(F)ccc2c1
• Target: Kras,Ras
• Solubility: DMSO: 50 mg/mL (83.25 mM), Sonication is recommended

Bioactivity

• Target IC50:
  KRas (G12D):0.2 pM (Kd)|KRas (G12D):< 2 nM
• In Vivo:
  METHODS: To test the antitumor activity in vivo, MRTX1133 (3-30 mg/kg, 10% Captisol in 50 mM citrate buffer pH 5.0) was intraperitoneally injected into nude-Foxn1nu mice bearing human pancreatic adenocarcinoma tumor Panc 04.03 twice daily for seven weeks. RESULTS: MRTX1133 exhibited dose-dependent antitumor activity, with 94% tumor growth inhibition observed at the 3 mg/kg group. Tumor regression of -62% and -73% was observed in the 10 mg/kg and 30 mg/kg groups, respectively. METHODS: To assay antitumor activity in vivo, MRTX1133 (0.5 mg/kg in 12.5% Cremophor+12.5% ethanol+75%, orally once daily) and Cetuximab (50 mg/kg, intraperitoneally once weekly) were administered to BALB/c nude mice harboring human colorectal tumors, LS531 or CACO-2 for twenty-one days. RESULTS: MRTX1133 significantly inhibited tumorigenesis in both in vivo models. The anti-tumor effect was further enhanced when MRTX1133 was combined with Cetuximab.
• In Vitro:
  METHODS: Human gastric cancer cells AGS (KRASG12D) and MKN1 (KRASWT) were treated with MRTX1133 (0-3 μM) for 72 h, and cell viability was measured by CTG method in 2D culture. RESULTS: The IC50 of MRTX1133 on AGS and MKN1 cells was 6 nM and >3000 nM, respectively. METHODS: Human gastric cancer cells AGS (KRASG12D) were treated with MRTX1133 (0-10 μM) for 3-72 h, and the expression levels of target proteins were detected by In-Cell Western method. RESULTS: MRTX1133 inhibited the p-ERK level of AGS with an IC50 of 2 nM. METHODS: Human pancreatic cancer cells SUIT2 (KRASG12D) were treated with MRTX1133 (60 nmol/L) for 24 h, and the expression levels of target proteins were detected by Western Blot. RESULTS: SUIT2 cells treated with MRTX1133 showed a significant decrease in pMEK1/2, a partial decrease in pERK1/2, and an initial decrease in pAKT followed by a recovery at a later time point. The levels of pEGFR and pHER2 decreased and recovered at 72 h.

Storage & Handling

• Storage: keep away from moisture | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

active, cells, Inhibitor, ERK, G12D, mutant, MRTX1133, MRTX-1133, MRTX 1133, inactive, KRAS G12D, KRAS, inhibit, tumor, states, Ras, phosphorylation, wild-type

Compound Identifiers

PubChem CID

162369732