MRTX1133 |
Catalog No.GC62699 |
MRTX1133은 비공유적이고 강력하며 선택적인 KRAS G12D 억제제입니다. MRTX1133은 스위치 II 포켓을 최적으로 채우고 3개의 치환기를 확장하여 단백질과 호의적으로 상호작용하여 0.2pM의 KRAS G12D에 대한 추정 KD를 생성합니다. MRTX1133은 SOS1 촉매에 의한 뉴클레오티드 교환 및/또는 KRAS G12D/GTP/RAF1 복합체의 형성을 방지하여 돌연변이 KRAS 의존성 신호 전달을 억제합니다. MRTX1133은 KRAS G12D 돌연변이를 선택적으로 억제하지만 KRAS 야생형 종양 세포는 억제하지 않습니다. MRTX1133은 세포 분석에서 한 자릿수 나노몰 활성을 가지며 KRAS G12D 돌연변이가 있는 종양 모델에서 생체 내 효능을 나타냅니다.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 2621928-55-8
Sample solution is provided at 25 µL, 10mM.
MRTX1133 is an exceptionally potent and selective KRASG12D inhibitor with high affinity (<2nM).[1]
In vitro, in the AGS cell line, MRTX1133 inhibited ERK phosphorylation with an IC50 of 2 nM. In the meanwhile, MRTX1133 was against the same cell line with an IC50 of 6 nM in a 2D viability assay.[1] In vitro efficacy test, in KRASG12D–mutant HPAC Cells, it indicated that treatment with 0.05 nM - 300 nM MRTX1133 has a dose-dependent pERK, pS6 & DUSP6 modulation.[2]
In vivo experiment it shown that treatment with 30 mg/kg of MRTX1133 intraperitoneally in CD-1 mice caused the sustained plasma exposure exceeding the free-fraction-adjusted pERK IC50 value in the KRASG12D mutant Panc 04.03 cell line for approximately 8 h. And in the Panc 04.03 xenograft tumor model, it suggested that MRTX1133 (3-30 mg/kg, i.p.) has 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.[1]
References:
[1].Wang X, Allen S, et al. Identification of MRTX1133, a Noncovalent, Potent, and Selective KRASG12D Inhibitor. J Med Chem. 2022 Feb 24;65(4):3123-3133.
[2].Swiatnicki M, Engel L, Shrestha R, Alves J, Goueli SA, Zegzouti H. Profiling oncogenic KRAS mutant drugs with a cell-based Lumit p-ERK immunoassay. SLAS Discov. 2022 Jun;27(4):249-257.
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