DDR1-IN-4

• CAT Number: I015374
• CAS Number: 2125676-13-1
• Molecular Formula: C23H20BrF3N6O3
• Molecular Weight: 565.34
• Purity: ≥95%
• Synonyms: 2-[4-bromo-2-oxo-1′-(1H-pyrazolo[4,3-b]pyridine-5-carbonyl)spiro[indole-3,4′-piperidine]-1-yl]-N-(2,2,2-trifluoroethyl)acetamide
• InChI: InChI=1S/C23H20BrF3N6O3/c24-13-2-1-3-17-19(13)22(21(36)33(17)11-18(34)28-12-23(25,26)27)6-8-32(9-7-22)20(35)15-5-4-14-16(30-15)10-29-31-14/h1-5,10H,6-9,11-12H2,(H,28,34)(H,29,31)
• InChIKey: UXEXYURPAPXPSR-UHFFFAOYSA-N
• SMILES: C1CN(CCC12C3=C(C=CC=C3Br)N(C2=O)CC(=O)NCC(F)(F)F)C(=O)C4=NC5=C(C=C4)NN=C5

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].

Reference

[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.
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