ALK5-IN-34 is an selective orally active activin receptor-like kinase (ALK) inhibitor. ALK5-IN-34 can inhibit the activity of ALK5-IN-34 with an IC50 value of ≤10 nM. ALK5-IN-34 also has inhibitory of tumor growth and can be used for the research of proliferative diseases, such as cancer.
ALK5-IN-34 (EX-11) has kinase inhibition of ALK5 with an IC50 value of ≤10 nM[1].ALK5-IN-34 has kinase selectivity of ALK2/ALK5 with an IC50 value of ＜100 nM[1].ALK5-IN-34 shows TGFB-RI inhibition (RD-SMAD receptor activity) with an IC50 value of ≤100 nM[1].ALK5-IN-34 (1 μM-10 nM) inhibits the expression of TGF-β-mediated alpha-SMA in a full concentration-dependent[1].ALK5-IN-34 (30, 300 and 3000 nM) suppresses the Treg frequency in a dose dependent manner[1].ALK5-IN-34 (0-0.1 μM; for 6 days or 7 days) inhibits FOXL2CI34W-driven growth in KGN and COV434 cells with IC50 values of 140 nM and >10 μM, respectively[1].ALK5-IN-34 (10, 100 and 1000 nM; 2 h) shows a dose-dependent decrease in pSmad2 in KGN cell line[1].ALK5-IN-34 (30, 300 nM; 24 h) reverses the upregulation of gene expression in dose dependentent[1].ALK5-IN-34 (30, 300 nM; 24 h) increases HLA class I expression in dose-dependent[1].
ALK5-IN-34 (EX-11) (oral; 10-100 mg/kg) reduces the phopho SMAD2 levels (p-SMAD2) in a dose dependent manner in A549 murine xenograft model[1].ALK5-IN-34 (oral; 75 mg/kg; 0-24 h) shows reversely correlated between PK and tumor PD (pSMAD2 levels)[1].ALK5-IN-34 (oral; 150 mg/kg; bid; for 22 days) increases overall survival in ES-2 ovarian cancer mouse xenograft model and can delay progression[1].ALK5-IN-34 (p.o.; 75, 150 mg/kg; twice a day; for 21days) shows tumor growth inhibition (TGI) and increases the survival when combining with anti-PD-L1/anti-PD-1 in Syngeneic TNBC Model and in Subcutaneous Cloudman S91 melanoma model[1].ALK5-IN-34 (oral; 300, 1000 mg/kg; bid for 5 days) has good tolerability and safety margin in Tolerability Model[1].
References:
[1]. Bettina FRANZ, et al. Alk-5 inhibitors and uses thereof. Patent. WO2022126133A1.