維塞諾作用機(jī)制 - Medchemexpress - MCE中國(guó)

1、Product Data SheetVercirnonCat. No.: HY-15724CAS No.: 698394-73-9分式: CHClNOS分量: 444.93作靶點(diǎn): CCR作通路: GPCR/G Protein; Immunology/Inflammation儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) 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制備儲(chǔ)備液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請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲(chǔ)備液；旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?6 個(gè)內(nèi)使，-20C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?1 個(gè)內(nèi)使。體內(nèi)實(shí)驗(yàn) 請(qǐng)根據(jù)您

3、的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍?。以下溶解案都?qǐng)先按照 In Vitro 式配制澄清的儲(chǔ)備液，再依次添加助溶劑：為保證實(shí)驗(yàn)結(jié)果的可靠性，澄 的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天 使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可 以通過(guò)加熱和/或超聲的式助溶1. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (5.62 mM); Clear solution此案可獲得 2.5 mg/mL (5.62 mM，飽和度未知) 的澄 溶液，此案不適于實(shí)驗(yàn)周 期

4、在半個(gè)以上的實(shí)驗(yàn)。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L 油中，混合均勻。Page 1 of 2 www.MedChemEBIOLOGICAL ACTIVITY物活性 Vercirnon (GSK-1605786)的研究。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IC & Target CCR910 nM (IC50)體外研究 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.體內(nèi)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