CH7057288 (C09-0823-291)

InformationCH7057288 is a potent and selectiveTRKinhibitor with IC50 values of 1.1 nM, 7.8 nM and 5.1 nM for TRKA, TRKB, and TRKC respectively.TargetsTrkA (Cell-free assay); TrkC (Cell-free assay); TrkB (Cell-free assay) 1.1 nM; 5.1 nM; 7.8 nMIn vitroCH7057288 shows selective inhibitory activity against TRKA, TRKB, and TRKC in cell-free kinase assays and suppresses proliferation of TRK fusion-positive cell lines, but not that of TRK-negative cell lines. CH7057288 suppresses mitogen-activated protein kinase (MAPK) and E2F pathways as downstream signaling of TRK fusion.In vivoStrong in vivo tumor growth inhibition is observed in subcutaneously implanted xenograft tumor models of TRK fusion-positive cells. Furthermore, in an intracranial implantation model mimicking brain metastasis, CH7057288 significantly induces tumor regression and improves event-free survival. CH7057288 induces potent tumor growth inhibition against all three models, with remarkable tumor regression in CUTO-3 and MO-91. CH7057288 exhibits dose-dependent exposure. Because of relatively short terminal half-life (3 to 5 hours), the plasma concentration 24 hours after dose dropped to approximately a few tenths to a hundredth of Tmax.Cell Research(from reference)Cell lines：The NSCLC cell line CUTO-3, CRC cell line KM12-Luc, and acute myeloid leukemia cell line MO-91 harbor MPRIP-NTRK1, TPM3-NTRK1, and ETV6-NTRK3, respectively Concentrations：0.01, 0.1 and 1 μM Incubation Time：2 h. Specifications and Purity: 99%. Molecular Formula: C32H31N3O5S. Molecular Weight: 569.67. PubChem CID: 131839646. Isomeric SMILES: CC1=CC(=CC(=N1)C#CC2=CC3=C(C=C2)C4=C(O3)C(C5=C(C4=O)C=CC(=C5)NS(=O)(=O)C)(C)C)C(=O)NC(C)(C)C.