ALK-IN-22

ALK-IN-22 (compound I-24) is a potent ALK inhibitor with IC50 values of 2.3, 3.7 and 2.9 nM for ALK, ALKL1196M and ALKG1202R, respectively. ALK-IN-22 down-regulated the phosphorylation of ALK and its downstream proteins. ALK-IN-22 induces apoptosis. ALK-IN-22 can be used for tumor research[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

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

ALK-IN-22 (compound I-24) (72 hours) has anti-proliferative activities against ALK-positive karpas299, H2228 and H3122 cell lines with IC50 values of 11, 37 and 27 nM, respectively[1]. ALK-IN-22 (compound I-24) (0-100 nM; 24 hours; H2228 cells) has inhibitory effect on ALK and downstream signaling AKT and ERK[1]. ALK-IN-22 (compound I-24) (0-100 nM; 48 hours; H2228 cells) can induce apoptosis and achieve cell cycle arrest in G1 phase[1]. Western Blot Analysis[1] Cell Line: H2228 cells Concentration: 0, 25, 50 and 100 nM Incubation Time: 24 hours Result: Downregulated the phosphorylation level of ALK and blocked the expressions of ALK downstream key signaling AKT, ERK along with their activated forms in a dose-dependent fashion. Apoptosis Analysis[1] Cell Line: H2228 cells Concentration: 0, 25, 50 and 100 nM Incubation Time: 48 hours Result: The apoptotic rates were 14.23%, 23.94% and 31.70% at concentrations of 25 nM, 50 nM and 100 nM, respectively. Cell Cycle Analysis[1] Cell Line: H2228 cells Concentration: 0, 25, 50 and 100 nM Incubation Time: 48 hours Result: The percentage of cells in the G1 phase increased from 49.72% to 58.51% in a dose-dependent fashion.

ALK-IN-22 (compound I-24) (25-50 mg/kg; i.g.; Twice daily, for 14 days) has antitumor efficacy in vivo[1]. ALK-IN-22 (compound I-24) (10 mg/kg; p.o.) shows the Cmax and t1/2 values of 345.7 ng/mL and 4.1 hours, respectively[1]. ALK-IN-22 (compound I-24) (2 mg/kg; i.v.) shows the CL and t1/2 values of 36.2 mL/min/kg and 2.5 hours, respectively[1]. Animal Model: Female BALB / c nude mice[1] Dosage: 25 and 50 mg/kg Administration: Intragastric; Twice daily, for 14 days. Result: The tumor growth inhibition (TGI) value of 50 mg/kg reached 93.5%. Animal Model: SD rats[1] Dosage: 2 and 10 mg/kg (Pharmacokinetic Analysis) Administration: Oral administration and intravenous injection Result: 1.19 Parameter F16 VP-16 Dose (i.v.) mg/kg 10 10 Cmax (ng/mL) 26952 17712 Tmax (min) 5 5 AUCplasma (min*ng/mL) 2878363 409528 T1/2 (min) 151 45 Vd (L/Kg) 0.2341 0.432 CL (L/min/kg) 0.001 0.007

[1]. Thacker PS, et al. Synthesis and biological evaluation of some coumarin hybrids as selective carbonic anhydrase IX and XII inhibitors. Bioorg Chem. 2020 Nov;104:104272.