Zotizalkib (TPX-0131) 是一种有效、选择性、CNS 渗透性和口服活性的野生型 ALK 抑制剂 (IC₅₀ 为 1.4 nM) 和 ALK 抗性突变，例如 G1202R (IC₅₀ 为 0.3 nM)、L1196M (IC₅₀ 为 0.3 nM)。Zotizalkib 具有很强的抗肿瘤活性。

Zotizalkib (TPX-0131) is a potent, selective, CNS-penetrant and orally active inhibitor of wild-type ALK (IC 50 of 1.4 nM) and ALK-resistant mutation, e.g. G1202R (IC 50 of 0.3 nM), L1196M (IC 50 of 0.3 nM). Zotizalkib has strong antitumor activities.

Solid

IC50: 1.4 nM (Wild-typr AKT); 0.2-6.6 nM (mutant ALK variants)

Zotizalkib potently inhibits wild-type ALK (IC50=1.4 nM) and 26 ALK resistance mutations. Zotizalkib inhibits C1156Y, E1210K/S1206C, L1198F/C1156Y, L1196M/L1198F, E1210K, L1196M, T1151M, deleted G1202, S1206R, G1202R/L1198F, F1174L, F1245C, R1275Q, and G1202R ALK mutations with IC50 values of <1 nM. Zotizalkib has IC50 values of 1-2 nM for the following ALK mutations: L1198F, L1152R, F1174S, T1151-L1152 insT, V1180L, G1269A, F1174C. Zotizalkib is less active against ALK mutations including I1171N, L1152P, D1203N, D1203N/E1210K, and G1269S, with IC50 values of 2-7 nM.
Zotizalkib is a potent inhibitor of ALK autophosphorylation in Ba/F3 cells expressing EML4-ALK G1202R solvent front, EML4-ALK G1202R/L1196M, or EML4-ALK G1202R/L1198F mutations, with IC50 values of approximately 3-10 nM.

Zotizalkib (2-10 mg/kg; p.o.; twice a day; for 2 weeks) treatment at 2 mg/kg, 5 mg/kg, and 10 mg/kg resulted in dose-dependent tumor growth inhibition (TGI) of 64%, 120%, and 200% (complete regression), respectively. has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model:

Room temperature in continental US; may vary elsewhere.

Powder -20°C 3 years；4°C 2 years

[1]. Brion W Murray, et al. TPX-0131, a Potent CNS-Penetrant, Next-Generation Inhibitor of Wild-Type ALK and ALK-Resistant Mutations. Mol Cancer Ther. 2021 Jun 22;molcanther.0221.2021.

In Vitro: DMSO : 25 mg/mL (55.88 mM; ultrasonic and warming and heat to 60°C)配制储备液