CAS 2598870-24-5
:Formula:C27H28N8O2
InChI:InChI=1S/C27H28N8O2/c1-3-37-21-9-22(26-23-12-30-31-27(23)32-35(26)16-21)18-5-6-24(28-11-18)33-14-19-8-20(15-33)34(19)13-17-4-7-25(36-2)29-10-17/h4-7,9-12,16,19-20H,3,8,13-15H2,1-2H3,(H,31,32)
InChI key:NYFLTHPPVNMNFL-UHFFFAOYSA-N
SMILES:CCOC1=CN2C(=C3C=NNC3=N2)C(=C1)C4=CN=C(C=C4)N5CC6CC(C5)N6CC7=CN=C(C=C7)OC
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APS03118
CAS:APS03118 is an orally effective, potent, and highly selective RET inhibitor. It broadly inhibits RET fusions and various mutations (including G810, V804, L730, and Y806 variants), with IC50 values generally below 1 nM (0.0952 nM for the wild type; mutation IC50s range from 0.00438 to 5.72 nM), demonstrating significant inhibitory activity against RETG810 mutations. APS03118 effectively suppresses the entire RET signaling pathway, including RET, Shc, and ERK1/2, and shows more than 20-fold selectivity over most off-target kinases, excluding FLT3 and YES. In vivo, APS03118 induces complete tumor regression in KIF5B-RET and CCDC6-RET V804M PDX mouse models and significantly extends survival in intracranial CCDC6-RET metastatic mouse models. This compound is applicable for research on RET-driven cancers resistant to selective RET inhibitors (SRI).Formula:C27H28N8O2Molecular weight:496.58
