| Identification | Back Directory | [Name]
AP26113 | [CAS]
1197958-53-4 | [Synonyms]
ALK-IN-12
5-Chloro-N4-[2-(dimethylphosphinyl)phenyl]-N2-[2-methoxy-4-(4-methyl-1-piperazinyl)phenyl]-2,4-pyrimidinediamine
2,4-Pyrimidinediamine, 5-chloro-N4-[2-(dimethylphosphinyl)phenyl]-N2-[2-methoxy-4-(4-methyl-1-piperazinyl)phenyl]- | [Molecular Formula]
C24H30ClN6O2P | [MOL File]
1197958-53-4.mol | [Molecular Weight]
500.96 |
| Hazard Information | Back Directory | [Uses]
ALK-IN-12 is a potent and orally active ALK inhibitor with an IC50 of 0.18 nM. ALK-IN-12 also inhibits IGF1R and InsR (IC50=20.3 and 90.6 nM). Antitumor activities[1]. | [in vivo]
ALK-IN-12 (10-50 mg/kg; orally; once daily for 13 consecutive days) shows dose-dependent antitumor activity[1].
ALK-IN-12 (3 mg/kg; i.v.; 6-8 week old female CD rats ) treatment shows AUC0-∞, CL, t1/2 and Vss are 3039 ng h/mL, 0.91 h kg, 6.6 hours and 6.12 L/kg, respectively[1].
ALK-IN-12 (10 mg/kg; p.o.; 6-8 week old female CD rats) treatment shows Cmax, AUC0-∞, tmax, t1/2 and F are 3254 ng/mL, 4056 ng h/mL, 6.0 hours, 12.5 hours and 39%, respectively[1]. | Animal Model: | Eight- to 10-week old female SCID/beige mice (Karpas-299 xenograft mouse model expressing the NPM-ALK fusion)[1] | | Dosage: | 10-50 mg/kg | | Administration: | Orally; once daily for 13 consecutive days | | Result: | Dose-dependent antitumor activity. Led to tumor stasis (50 mg/kg dose).
|
| [References]
[1] Huang WS, et al. Discovery of Brigatinib (AP26113), a Phosphine Oxide-Containing, Potent, Orally Active Inhibitor of Anaplastic Lymphoma Kinase. J Med Chem. 2016;59(10):4948-4964. DOI:10.1021/acs.jmedchem.6b00306 |
|
|