Zidesamtinib

Zidesamtinib (NVL-520) is a potent, selective, orally active and brain-penetrant inhibitor of diverse ROS1 fusions and resistance mutations, with IC50s of 0.7 and 7.9 nM for wild-type ROS1 and ROS1 G2032R, respectively, and spares TRK inhibition. Zidesamtinib can be used for the research of cancer[1].

Research Areas >> Cancer

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> ROS

Zidesamtinib (72 h) inhibits the growth of seven cell lines expressing wild-type ROS1 fusions, with average IC50s of 0.4 nM[1]. Zidesamtinib (72 h) inhibits the growth of six cell lines harboring ROS1 fusions with the G2032R mutation, with average IC50s of 1.6 nM[1]. Zidesamtinib (72 h) potently inhibits the non-G2032R ROS1 mutants, with IC50s ≤ 1.5 nM[1]. Zidesamtinib (10-1000 nM; 4 weeks) suppresses colony formation in NIH3T3 cells expressing wild-type ROS1 fusions and expressing ROS1 fusions with G2032R[1].

Zidesamtinib (0.04-15 mg/kg; p.o. twice daily for 28 d) induces tumor regression at all doses ≥0.2 mg/kg in wild-type ROS1 xenograft models[1]. Animal Model: Female athymic Nude-Foxn1nu mice were implanted subcutaneously with tumor fragments from model CTG-0848[1] Dosage: 0.04, 0.2, 1, 5, 15 mg/kg Administration: Oral gavage twice daily for 21 days Result: Inhibited the tumor volumes.

[1]. Drilon A, et, al. NVL-520 is a selective, TRK-sparing, and brain-penetrant inhibitor of ROS1 fusions and secondary resistance mutations. Cancer Discov. 2022 Dec 13;CD-22-0968.