DDR1 inhibitor 2.45

Research use only, not for human use.

DDR1 inhibitor 2.45 (Compound 2.45) is a novel potent, selective, bioavailable Discoidin Domain Receptor 1 (DDR1) inhibitor with IC50 of 29 nM.

DDR1 inhibitor 2.45 (Compound 2.45) is a novel potent, selective, bioavailable Discoidin Domain Receptor 1 (DDR1) inhibitor with IC50 of 29 nM, displays 64-fold selectivity over DDR2 in biochemical assays; also possesses excellent kinome selectivity against a kinase panel of 468 kinases; Compound 2.45 inhibits DDR1 phosphorylation (70% inhibition at 1 uM in HT1080 cells overexpressing DDR1) and recruitment of SHC1 in vitro, and modulates phenotype of collagen stimulated renal epithelial cells; Compound 2.45 preserves renal function and reduces tissue damage in Col4a3 / mice (the preclinical mouse model of Alport syndrome).

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.

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. Animal Model:Col4a3–/– mice, a mouse model phenocopying Alport syndrome.Dosage:90 mg/kg.Administration:Injected intraperitoneally daily.Result:Resulted in a significant reduction of fibrosis evaluated by Picro Sirius Red, smooth muscle actin staining, and collagen I accumulation.Significantly reduces the levels of pDDR1 in Col4a3 knockout mice compared to controls.

Compound 2.45

Tyrosine Kinase

DDR

DDR

——

——

2125676-13-1

565.351

C23H20BrF3N6O3

>98% (HPLC)

In Vitro:?DMSO : 250 mg/mL (442.21 mM)

C1CN(CCC12C3=C(C=CC=C3Br)N(C2=O)CC(=O)NCC(F)(F)F)C(=O)C4=NC5=C(C=C4)NN=C5

2-(4-bromo-2-oxo-1'-(1H-pyrazolo[4,3-b]pyridine-5-carbonyl)spiro[indoline-3,4'-piperidin]-1-yl)-N-(2,2,2-trifluoroethyl)acetamide

(-20℃)

With Ice Pack

≥ 2 years