VU6015929
目录号 : GC39301VU6015929 is a selective Discoidin Domain Receptor 1/2 (DDR1/2) inhibitor with IC50 of 4.67 nM and 7.39 nM for DDR1 and DDR2, respectively. VU6015929 potently inhibits collagen-IV production.
Cas No.:2442597-56-8
Sample solution is provided at 25 µL, 10mM.
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VU6015929 is a selective Discoidin Domain Receptor 1/2 (DDR1/2) inhibitor with IC50 of 4.67 nM and 7.39 nM for DDR1 and DDR2, respectively. VU6015929 potently inhibits collagen-IV production.
[1] Daniel E Jeffries, et al. ACS Med Chem Lett. 2019 Nov 25;11(1):29-33.
Cas No. | 2442597-56-8 | SDF | |
Canonical SMILES | O=C(NC1=CC=CC(OC(F)(F)F)=C1)C2=CC(NCC3=CC(C4=NN(C)C=C4)=CN=C3)=C(F)C=C2 | ||
分子式 | C24H19F4N5O2 | 分子量 | 485.43 |
溶解度 | DMSO: 250 mg/mL (515.01 mM) | 储存条件 | Store at -20°C |
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1 mg | 5 mg | 10 mg | |
1 mM | 2.06 mL | 10.3001 mL | 20.6003 mL |
5 mM | 0.412 mL | 2.06 mL | 4.1201 mL |
10 mM | 0.206 mL | 1.03 mL | 2.06 mL |
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Discovery of VU6015929: A Selective Discoidin Domain Receptor 1/2 (DDR1/2) Inhibitor to Explore the Role of DDR1 in Antifibrotic Therapy
ACS Med Chem Lett 2019 Nov 25;11(1):29-33.PMID:31938459DOI:10.1021/acsmedchemlett.9b00382.
Herein, we report the discovery of a potent and selective dual DDR1/2 inhibitor, 7e (VU6015929), displaying low cytotoxicity, good kinome selectivity, and possessing an acceptable in vitro DMPK profile with good rodent in vivo pharmacokinetics. VU6015929 potently blocks collagen-induced DDR1 activation and collagen-IV production, suggesting DDR1 inhibition as an exciting target for antifibrotic therapy.
Identification of novel discoidin domain receptor 1 (DDR1) inhibitors using E-pharmacophore modeling, structure-based virtual screening, molecular dynamics simulation and MM-GBSA approaches
Comput Biol Med 2022 Mar;142:105217.PMID:35032738DOI:10.1016/j.compbiomed.2022.105217.
Dysregulation of the discoidin domain receptor (DDR1), a collagen-activated receptor tyrosine kinase, has been linked to several human cancer diseases including non-small cell lung carcinoma (NSCLC), ovarian cancer, glioblastoma, and breast cancer, in addition to several inflammatory and neurological conditions. Although there are some selective DDR1 inhibitors that have been discovered during the last two decades, a combination of elevated cytotoxicity, kinome selectivity and/or poor DMPK profile has prevented more in-depth studies from being performed. As such, no DDR1 inhibitor has reached clinical investigation to date, forming an urgent need to develop specific DDR1 inhibitor(s) using various drug discovery means. However, the recent discovery of VU6015929, a potent and selective DDR1 kinase inhibitor, with enhanced physiochemical and DMPK properties in addition to its clean kinome profile marked a milestone in the development of DDR1 inhibitors. Herein, VU6015929 was used to construct a 3D e-pharmacophore model which was validated via calculating the difference of score between the active compounds and decoys. The validated e-pharmacophore model was then utilized to screen 20 million drug-like compounds obtained from the freely accessible Zinc database. The generated hits were ranked using high throughput virtual screening technique (HTVS), and the top 8 small molecules were subjected to a molecular docking study and MM-GBSA calculations. Protein-ligand complexes of compounds 1, 2, 3 and the standard compound (VU6015929) were performed for 100 ns and compared with the DDR1 unbound protein state and the DDR1 bound to a co-crystallized ligand. The molecular docking, MD and MM-GBSA outputs revealed compounds 1-3 as potential DDR1 inhibitors, with compound 2 displaying superior binding affinity, comparable binding stability and average binding free energy for the ligand-enzyme complex compared to VU6015929.