LOXO-292

RET激酶抑制剂；抑制HEK293细胞中表达的KIF5B-RET融合蛋白的磷酸化（IC50=4nM）；选择性抑制含有RET突变或基因融合的癌细胞增殖，包括含有RETM918T的MZ-CRC-1髓样甲状腺癌细胞和CCDC6-RET基因融合阳性的TPC-1甲状腺癌细胞，抑制量达20至1,700倍；以30mg/kg的剂量提高CCDC6-RET基因融合阳性原位PDX小鼠脑癌模型的生存率。A RET kinase inhibitor; inhibits phosphorylation of a KIF5B-RET fusion protein expressed in HEK293 cells (IC50 = 4 nM); 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; improves survival in a CCDC6-RET gene fusion positive orthotopic PDX mouse model of brain cancer at 30 mg/kg.分子式C29H31N7O3分子量525.6N#CC1=C2C(C3=CN=C(N4CC5N(C(C5)C4)CC6=CN=C(OC)C=C6)C=C3)=CC(OCC(C)(O)C)=CN2N=C1