维塞诺作用机制 - Medchemexpress - MCE中国

1、Product Data SheetVercirnonCat. No.: HY-15724CAS No.: 698394-73-9分式: CHClNOS分量: 444.93作靶点: CCR作通路: GPCR/G Protein; Immunology/Inflammation储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 25 mg/mL (56.19 mM)H2O : 0.1 mg/mL (insoluble)* means soluble, but saturati

2、on unknown.SolventMass1 mg 5 mg 10 mgConcentration制备储备液1 mM 2.2475 mL 11.2377 mL 22.4754 mL5 mM 0.4495 mL 2.2475 mL 4.4951 mL10 mM 0.2248 mL 1.1238 mL 2.2475 mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 储存时，请在 6 个内使，-20C 储存时，请在 1 个内使。体内实验 请根据您

3、的实验动物和给药式选择适当的溶解案。以下溶解案都请先按照 In Vitro 式配制澄清的储备液，再依次添加助溶剂：为保证实验结果的可靠性，澄 的储备液可以根据储存条件，适当保存；体内实验的作液，建议您现现配，当天 使； 以下溶剂前显的百分 指该溶剂在您配制终溶液中的体积占；如在配制过程中出现沉淀、析出现象，可 以通过加热和/或超声的式助溶1. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (5.62 mM); Clear solution此案可获得 2.5 mg/mL (5.62 mM，饱和度未知) 的澄 溶液，此案不适于实验周 期

4、在半个以上的实验。以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 900 L 油中，混合均匀。Page 1 of 2 www.MedChemEBIOLOGICAL ACTIVITY物活性 Vercirnon (GSK-1605786)的研究。种有效的，选择性的，可服的 CCR9 拮抗剂，IC50 值为 10 nM，可于炎性肠疾病IC & Target CCR910 nM (IC50)体外研究 Vercirnon (GSK-1605786) is an orally bioavailable, selective, and potent antagoni

5、st of human CCR9. Vercirnon inhibitsCCL25-induced calcium mobilization with an IC50 value of 5.4 0.7 nM. Vercirnon is also a potent inhibitor of CCL25-induced Molt-4 chemotaxis with an IC50 of 3.5 0.3 nM. Vercirnon shows inhibitory activity against Molt-4 migrationwith an IC50 of 33.4 1.3 nM in 100%

6、 human AB serum. Moreover, Vercirnon suppresses the binding of 3H CCX807to Molt-4 cells with an IC50 of 6 nM. Vercirnon inhibits the chemotaxis of Baf-3/CCR9A cells as well as Baf-3/CCR9Acells with IC50s of 2.8 1.1 nM and 2.6 0.7 nM, respectively. Vercirnon potently inhibits CCL25-induced chemotaxis

7、with an IC50 value of 6.8 1.7 nM in buffer, and exhibits inhibition on RA-cultured cell CCL25-medidated chemotaxisin 100% human AB serum with an IC50 of 141 13 nM1.体内研究 Vercirnon (GSK-1605786) (10, 50 mg/kg twice daily) protects from the severe inflammation associated with TNF-overexpression in the

8、TNFARE Mouse Model. Vercirnon (50 mg/kg c.c. twice daily) blocks the colitis-associatedweight loss inherent in the mdr1a/ model, and also abrogates growth arrest in the colitis mdr1a / mice2.PROTOCOLCell Assay 1 Cells are harvested by centrifugation and resuspended in chemotaxis buffer consisting of

9、 HBSS with 0.1% BSA at adensity of 107 cells/mL. For assays designed to determine Vercirnon potency in the presence of human serum, cellsare resuspended in 100% human AB serum from pooled donors. Equal volumes of cell suspension and dilutedVercirnon are mixed and incubated for 10 min at room tempera

10、ture. Twenty microliters of the mixture is transferredto the upper chamber of the chemotaxis chamber. After a 120-min incubation at 37C, the assay is terminated byremoval of cell drops from the top of the filter. Migration signal is determined by adding 5 L of CyQUANT solutionto each well in the low

11、er chemotaxis chamber and measuring the intensity of fluorescence on a Spectrafluor Plusplate reader1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice2Administration 2 Female mdr1a/ and wild-type FVB mice are used in the assay. CCX025, formul

12、ated in 1% hydroxypropylmethylcellulose, is dosed at 100 mg/kg s.c. once daily. Vercirnon, formulated in 5% Cremophor, is dosed at 50mg/kg c.c. twice daily. During the course of the study, body weights and the incidence of diarrhea are recorded on aweekly basis. Any animals that exhibits weight loss

13、 of greater than 20% of their peak body weight are euthanized.Final body weights for any euthanized or dead animals are carried forward for data analysis. Diarrhea is scored on a0-5 scale; when animals reach a score of 3, their diarrhea is constant and irreversible and is thus considered asestablish

14、ed diarrhea2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Walters MJ, et al. Characterization of CCX282-B, an orally bioavailable antagonist of the CCR9 chemokine receptor, for treatment of inflammatory boweldisease. 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.Page 2 of 3 www.MedChemE3. Zhang J, et al. Biarylsulfonamide CCR9 inhibitors for inflammatory bowel disease. Bioorg Med Chem Lett. 2015 Sep 1;25(17):3661