Vercirnon-GSK-1605786-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEVercirnonCat. No.: HY-15724CAS No.: 698394-73-9Synonyms: GSK-1605786; CCX282-B; Traficet-EN分式: CHClNOS分量: 444.93作靶點: CCR作通路: GPCR/G Protein; Immunology/Inflammation儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1

2、 month溶解性數(shù)據(jù)體外實驗 DMSO : 25 mg/mL (56.19 mM)H2O : 90% corn oilSolubility: 2.5 mg/mL (5.62 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEBIOLOGICAL ACTIVITY物活性 Vercirnon種有效的，選擇性的，可服的 CCR9 拮抗劑，IC50 值為 10 nM，可于炎性腸疾病的研究。IC50 & Target CCR910 nM (IC50)體外研究 Vercirnon (CCX282-B) is an or

3、ally bioavailable, selective, and potent antagonist of human CCR9. Vercirnoninhibits CCL25-induced calcium mobilization with an IC50 value of 5.4 0.7 nM. Vercirnon is also a potentinhibitor of CCL25-induced Molt-4 chemotaxis with an IC50 of 3.5 0.3 nM. Vercirnon shows inhibitoryactivity against Molt

4、-4 migration with an IC50 of 33.4 1.3 nM in 100% human AB serum. Moreover,Vercirnon suppresses the binding of 3H CCX807 to Molt-4 cells with an IC50 of 6 nM. Vercirnon inhibits thechemotaxis of Baf-3/CCR9A cells as well as Baf-3/CCR9A cells with IC50s of 2.8 1.1 nM and 2.6 0.7 nM,respectively. Verci

5、rnon potently inhibits CCL25-induced chemotaxis with an IC50 value of 6.8 1.7 nM inbuffer, and exhibits inhibition on RA-cultured cell CCL25-medidated chemotaxis in 100% human AB serumwith an IC50 of 141 13 nM 1.體內(nèi)研究 Vercirnon (10, 50 mg/kg twice daily) protects from the severe inflammation associat

6、ed with TNF-overexpression in the TNFARE Mouse Model. Vercirnon (50mg/kg c.c. twice daily) blocks the colitis-associated weight loss inherent in the mdr1a/ model, and also abrogates growth arrest in the colitis mdr1a/ mice 2.PROTOCOLCell Assay 1 Cells are harvested by centrifugation and resuspended

7、in chemotaxis buffer consisting of HBSS with 0.1%BSA at a density of 107 cells/mL. For assays designed to determine Vercirnon potency in the presence ofhuman serum, cells are resuspended in 100% human AB serum from pooled donors. Equal volumes of cellsuspension and diluted Vercirnon are mixed and in

8、cubated for 10 min at room temperature. Twentymicroliters of the mixture is transferred to the upper chamber of the chemotaxis chamber. After a 120-minincubation at 37C, the assay is terminated by removal of cell drops from the top of the filter. Migration signalis determined by adding 5 L of CyQUAN

9、T solution to each well in the lower chemotaxis chamber andmeasuring the intensity of fluorescence on a Spectrafluor Plus plate reader 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 2Administration 2 Female mdr1a/ and wild-type FVB mice a

10、re used in the assay. CCX025, formulated in 1% hydroxypropylmethylcellulose, is dosed at 100mg/kg s.c. once daily. Vercirnon, formulated in 5% Cremophor, is dosed at50mg/kg c.c. twice daily. During the course of the study, body weights and the incidence of diarrhea arerecorded on a weekly basis. Any

11、 animals that exhibits weight loss of greater than 20% of their peak bodyweight are euthanized. Final body weights for any euthanized or dead animals are carried forward for dataanalysis. Diarrhea is scored on a 0-5 scale; when animals reach a score of 3, their diarrhea is constant andirreversible a

12、nd is thus considered as established diarrhea 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEREFERENCES1. Walters MJ, et al. Characterization of CCX282-B, an orally bioavailable antagonist of the CCR9

13、chemokine receptor, for treatment ofinflammatory bowel disease. J Pharmacol Exp Ther. 2010 Oct;335(1):61-9.2. Bekker P, et al. CCR9 Antagonists in the Treatment of Ulcerative Colitis. Mediators Inflamm. 2015;2015:628340.3. Zhang J, et al. Biarylsulfonamide CCR9 inhibitors for inflammatory bowel disease. Bioorg Med Chem Lett. 2015 Sep 1;25(17):3661-4.MceP