Pralsetinib

Pralsetinib is an inhibitor of RET (IC50s = 0.4, 0.3, 0.4, and 0.4 nM for wild-type RET, RETV804L, RETV804M, and RETM918T, respectively). It is selective for RET over VEGFR2 (IC50 = 35 nM) and a panel of 371 kinases at 300 nM. Pralsetinib also inhibits a fusion protein of coiled-coil domain-containing protein 6 with RET (CCDC6-RET) and autophosphorylation of RET in Ba/F3 cells expressing a fusion protein of kinesin-1 heavy chain with RET (KIF5B-RET, IC50s = 0.4 and 5 nM, respectively). It induces tumor regression in a KIF5B-RET-positive patient-derived xenograft (PDX) mouse model of non-small cell lung cancer (NSCLC) when administered at a dose of 30 mg/kg. Formulations containing pralsetinib have been used in the treatment of metastatic RET-fusion-positive NSCLC.Formal Name: cis-N-[(1S)-1-[6-(4-fluoro-1H-pyrazol-1-yl)-3-pyridinyl]ethyl]-1-methoxy-4-[4-methyl-6-[(5-methyl-1H-pyrazol-3-yl)amino]-2-pyrimidinyl]-cyclohexanecarboxamide. CAS Number: 2097132-94-8. Synonyms: BLU-667. Molecular Formula: C27H32FN9O2. Formula Weight: 533.6. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: DMSO: Soluble, Methanol: Slightly soluble, Water: Slightly soluble. SMILES: C[C@@H](C1=CN=C(N2N=CC(F)=C2)C=C1)NC([C@]3(CC[C@@](C4=NC(C)=CC(NC5=NNC(C)=C5)=N4)([H])CC3)OC)=O. InChi Code: InChI=1S/C27H32FN9O2/c1-16-11-22(33-23-12-17(2)35-36-23)34-25(31-16)19-7-9-27(39-4,10-8-19)26(38)32-18(3)20-5-6-24(29-13-20)37-15-21(28)14-30-37/h5-6,11-15,18-19H,7-10H2,1-4H3,(H,32,38)(H2,31,33,34,35,36)/t18-,19-,27+/m0/s1. InChi Key: GBLBJPZSROAGMF-RWYJCYHVSA-N.