MRTX1133 |
| Katalog-Nr.GC62699 |
MRTX1133 ist ein nicht-kovalenter, potenter und selektiver KRAS G12D-Inhibitor. MRTX1133 fÜllt die Schalter-II-Tasche optimal und erweitert drei Substituenten, um gÜnstig mit dem Protein zu interagieren, was zu einer geschÄtzten KD gegen KRAS G12D von 0,2 pM fÜhrt. MRTX1133 verhindert den SOS1-katalysierten Nukleotidaustausch und/oder die Bildung des KRAS G12D/GTP/RAF1-Komplexes und hemmt dadurch die mutante KRAS-abhÄngige Signaltransduktion. MRTX1133 hemmt selektiv KRAS-G12D-Mutanten, aber nicht KRAS-Wildtyp-Tumorzellen. MRTX1133 hat eine AktivitÄt im einstelligen nanomolaren Bereich in zellulÄren Assays und eine ausgeprÄgte In-vivo-Wirksamkeit in Tumormodellen mit KRAS G12D-Mutationen.
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.
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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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