Tesetaxel

Tesetaxel (DJ-927) is an orally active and brain-penetrant taxane tubulin inhibitor. Tesetaxel inhibits tubulin depolymerization with an IC₅₀ of 0.44 μM. Tesetaxel inhibits cancer cells proliferation and shows potent antitumor activity against P-glycoprotein-positive cancer cells. Tesetaxel can be used for the research of cancer, such as solid tumors, liver metastasis, and advanced breast cancer^[1][2]. In Vitro:Tesetaxel inhibits porcine brain tubulin depolymerization with an IC₅₀ of 0.44 μM and does not inhibit tubulin polymerization (IC₅₀ >2.0 μM)^[1].
Tesetaxel shows mean GI₅₀ value of 0.550 ng/mL against the 23 different human tumor cells^[1].
Tesetaxel exhibits greater cytotoxicity than Paclitaxel (HY-B0015) and Docetaxel (HY-B0011) against P-gp-overexpressing resistant PC-6 and HCT116 cell lines^[1].
Tesetaxel (10 days) inhibits colony formation of M5076 cells with an IC₅₀ of 5.5 ng/mL, and its activity is unaffected by the P-gp modulator Verapamil (HY-14275)^[1]. In Vivo:Tesetaxel (DJ-927) (9.80 mg/kg; p.o.; q8d; 2 doses) achieves greater than 90% tumor growth inhibition against P-glycoprotein-positive human colon cancer DLD-1 xenografts in male BALB/c-nu/nu mice^[1].
Tesetaxel (DJ-927) (12 mg/kg; p.o.; single dose) achieves greater than 90% tumor growth inhibition against P-glycoprotein-positive human breast cancer DU4475 xenografts in male BALB/c-nu/nu mice^[1].
Tesetaxel (DJ-927) (9.8 mg/kg; p.o. or i.v.; once every 8 days; 2 doses) prolongs the life o in male C57BL/6 mice with P-glycoprotein-positive M5076 liver metastatic tumors^[1].