DDR1 inhibitor 2.45

Biological Activity

DDR1-IN-4 (Compound 2.45) is a selective and potent Discoidin Domain Receptor 1 (DDR1) autophosphorylation inhibitor, with IC50 values of 29 nM and 1.9 μM for DDR1 and DDR2, respectively[1]. DDR1-IN-4 (Compound 2.45) shows a clear dose-dependent inhibition of DDR1 phosphorylation in HT1080 cells overexpressing DDR1, with greater than 70% inhibition of phosphorylation at a concentration of 1 μM, and retaining selectivity over inhibition of DDR2[1]. DDR1-IN-4 (Compound 2.45, ip, 90 mg/kg) preserves renal function and reduces tissue damage in Col4a3-/- mice (the preclinical mouse model of Alport syndrome) when employing a therapeutic dosing regime, indicating the real therapeutic value of selectively inhibiting DDR1 phosphorylation in vivo[1].

References

[1]. Hans Richter, et al. DNA-Encoded Library-Derived DDR1 Inhibitor Prevents Fibrosis and Renal Function Loss in a Genetic Mouse Model of Alport Syndrome. ACS Chem Biol. 2019 Jan 18;14(1):37-49.