LOXO-292

LOXO-292 is an inhibitor of the receptor tyrosine kinase RET. It inhibits the phosphorylation of a KIF5B-RET fusion protein expressed in HEK293 cells (IC50 = 4 nM). LOXO-292 selectively inhibits proliferation of cancer cells containing RET mutations or gene fusions, including RETM918T-containing MZ-CRC-1 medullary thyroid and CCDC6-RET gene fusion-positive TPC-1 thyroid cancer cells, by 20 to 1,700-fold. It improves survival in a CCDC6-RET gene fusion-positive orthotopic patient-derived xenograft (PDX) mouse model of brain cancer when administered at a dose of 30 mg/kg. Formulations containing LOXO-292 have been used in the treatment of RET mutation- or gene fusion-positive lung or thyroid cancers.Formal Name: 6-(2-hydroxy-2-methylpropoxy)-4-[6-[6-[(6-methoxy-3-pyridinyl)methyl]-3,6-diazabicyclo[3.1.1]hept-3-yl]-3-pyridinyl]-pyrazolo[1,5-a]pyridine-3-carbonitrile. CAS Number: 2152628-33-4. Synonyms: ARRY-192, Selpercatinib. Molecular Formula: C29H31N7O3. Formula Weight: 525.6. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 1 mg/ml, DMSO: 1 mg/ml. lambdamax: 239, 335 nm. SMILES: N#CC1=C2C(C3=CN=C(N4CC5N(C(C5)C4)CC6=CN=C(OC)C=C6)C=C3)=CC(OCC(C)(O)C)=CN2N=C1. InChi Code: InChI=1S/C29H31N7O3/c1-29(2,37)18-39-24-9-25(28-21(10-30)13-33-36(28)17-24)20-5-6-26(31-12-20)34-15-22-8-23(16-34)35(22)14-19-4-7-27(38-3)32-11-19/h4-7,9,11-13,17,22-23,37H,8,14-16,18H2,1-3H3. InChi Key: XIIOFHFUYBLOLW-UHFFFAOYSA-N.