| Identification | Back Directory | [Name]
DDR1 inhibitor 2.45 | [CAS]
2125676-13-1 | [Synonyms]
DDR1-IN-4
DDR1-IN-2.45
DDR1 inhibitor 2.45
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
Spiro[3H-indole-3,4'-piperidine]-1(2H)-acetamide, 4-bromo-2-oxo-1'-(1H-pyrazolo[4,3-b]pyridin-5-ylcarbonyl)-N-(2,2,2-trifluoroethyl)- | [Molecular Formula]
C23H20BrF3N6O3 | [MDL Number]
MFCD34469287 | [MOL File]
2125676-13-1.mol | [Molecular Weight]
565.34 |
| Hazard Information | Back Directory | [Uses]
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]. | [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]. | [in vivo]
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]. | Animal Model: | Col4a3–/– mice, a mouse model phenocopying Alport syndrome[1]. | | 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.
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| [IC 50]
DDR1: 29 nM (IC50); DDR2: 1900 nM (IC50) | [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. |
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