TPX-0131 is a potent, selective, CNS-penetrant and orally active inhibitor of wild-type ALK (IC50 of 1.4 nM) and ALK-resistant mutation, e.g. G1202R (IC50 of 0.3 nM), L1196M (IC50 of 0.3 nM). TPX-0131 has strong antitumor activities.

Product information

CAS Number: 2648641-36-3

Molecular Weight: 447.41

Formula: C21H20F3N5O3

Chemical Name: (18S)-18-(difluoromethyl)-13-fluoro-7,7-dimethyl-9,20-dioxa-1,2,6,17,23-pentaazapentacyclo[19.3.1.0⁴,²⁴.0¹⁰,¹⁵.0¹⁷,²²]pentacosa-2,4(24),10,12,14,21(25),22-heptaen-5-one

Smiles: CC1(C)COC2=CC=C(F)C=C2CN2[C@@H](COC3=CN4N=CC(C(=O)N1)=C4N=C23)C(F)F

InChiKey: ILAMRXVQSGVCJX-AWEZNQCLSA-N

InChi: InChI=1S/C21H20F3N5O3/c1-21(2)10-32-15-4-3-12(22)5-11(15)7-28-14(17(23)24)9-31-16-8-29-18(26-19(16)28)13(6-25-29)20(30)27-21/h3-6,8,14,17H,7,9-10H2,1-2H3,(H,27,30)/t14-/m0/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

TPX-0131 potently inhibits wild-type ALK (IC50 = 1.4 nM) and 26 ALK resistance mutations. TPX-0131 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. TPX0131 has IC50 values of 1-2 nM for the following ALK mutations: L1198F, L1152R, F1174S, T1151-L1152 insT, V1180L, G1269A, F1174C. TPX-0131 is less active against ALK mutations including I1171N, L1152P, D1203N, D1203N/E1210K, and G1269S, with IC50 values of 2-7 nM. TPX-0131 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.

In Vivo:

TPX-0131 (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.

Products are for research use only. Not for human use.