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Background Information:
RMC-4550 is a potent, selective and orally available small molecule allosteric inhibitor of SHP2, acting by stabilizing the SHP2 protein in an inactive conformation that is unable to transmit cell growth signals. It inhibits purified, activated full length human SHP2 with an IC50 of 1.6 nM, and has cellular IC50 of 39 nM in PC9 cells with a pERK readout. RMC-4550 has no detectable inhibitory activity up to 10 µM against the catalytic domain of SHP2, a panel of 14 additional protein phosphatases, and a panel of 468 protein kinases. RMC-4450 as a single agent was found to attenuate signal transduction through the RAS-MAP kinase cascade, reduce tumor growth and cause tumor cell death in preclinical xenograft studies of human tumors carrying select mutations in the RAS-MAP kinase pathway.
Reference:
1. R. J. Nichols, et al, RAS nucleotide cycling underlies the SHP2 phosphatase dependence of mutant BRAF-, NF1- and RAS-driven cancers, Nature Cell Biology, Volume 20, pages1064–1073 (2018).
APIM050062: RMC-4550 (RMC4550)
CAS No.: 2172651-73-7.
Molecular Formula: C21H26Cl2N4O2.
Molecular Weight: 437.4.
Purity: >99.5% Chemically and Stereomerically Pure by achiral and chiral HPLCs.
QC: Achiral and Chiral HPLCs, MS, NMR, and Elemental Analysis Report.
Solubility: Refer to Certificate of Analysis.
Storage: Refer to Certificate of Analysis.
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