Vercirnon是一种新型的、具有口服活性的CCR9趋化因子受体选择性拮抗剂，抑制CCR9介导的Molt-4细胞钙离子动员和趋化作用的IC₅₀值分别为5.4nM和3.4nM
Cas No.:698394-73-9
Sample solution is provided at 25 µL, 10mM.
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Vercirnon is a novel, orally active selective antagonist of the CCR9 chemokine receptor, with IC₅₀ values of 5.4nM and 3.4nM for inhibiting CCR9‑mediated calcium mobilization and chemotaxis in Molt‑4 cells, respectively [1-2]. By specifically blocking the binding of the ligand CCL25 to the CCR9 receptor expressed on T cells, Vercirnon inhibits the migration and recruitment of T cells to the intestinal mucosa, thereby alleviating inflammation in inflammatory bowel disease[3-4].
In vitro, treatment of SACC‑LM cells with Vercirnon (10nM) for 48 hours, Vercirnon significantly suppressed cell proliferation, migration, and invasion, while promoting apoptosis [5]. In isolated CD1 mouse islets, co‑treatment with Vercirnon (10nM) and CCL25 (50nM) for 1 hour, Vercirnon significantly enhanced glucose‑stimulated insulin secretion and increased cAMP accumulation[6].
In vivo, Vercirnon (10mg/kg or 50mg/kg) administered subcutaneously twice daily for 10 weeks in a Crohn’s disease mouse model, Vercirnon significantly improved intestinal inflammation resembling Crohn’s disease[7]. Vercirnon (50mg/kg) given subcutaneously twice daily for 20 weeks in mdr1a⁻/⁻ mice markedly ameliorated ulcerative colitis‑associated weight loss and colonic inflammation[8].
References:
[1] Vallet-Pichard A, Pol S. Grazoprevir/elbasvir combination therapy for HCV infection. Therap Adv Gastroenterol. 2017 Jan;10(1):155-167.
[2] Arseneau KO, Cominelli F. Vercirnon for the treatment of Crohn's disease. Expert Opin Investig Drugs. 2013 Jul;22(7):907-13.
[3] Haberer LJ, McSherry I, Cargill A, et al. Effects of vercirnon on the activity of CYP3A4, CYP2C19 and CYP2C8 enzymes and BCRP and OATP1B1 transporters using probe substrates. Eur J Clin Pharmacol. 2014 Jan;70(1):37-45.
[4] Zhang J, Romero J, Chan A, et al. Biarylsulfonamide CCR9 inhibitors for inflammatory bowel disease. Bioorg Med Chem Lett. 2015 Sep 1;25(17):3661-4.
[5] Chai S, Wen Z, Zhang R, et al. CCL25/CCR9 interaction promotes the malignant behavior of salivary adenoid cystic carcinoma via the PI3K/AKT signaling pathway. PeerJ. 2022 Aug 19;10:e13844.
[6] Atanes P, Lee V, Huang GC, et al. The role of the CCL25-CCR9 axis in beta-cell function: potential for therapeutic intervention in type 2 diabetes. Metabolism. 2020 Dec;113:154394.
[7] Walters MJ, Wang Y, Lai N, et al. Characterization of CCX282-B, an orally bioavailable antagonist of the CCR9 chemokine receptor, for treatment of inflammatory bowel disease. J Pharmacol Exp Ther. 2010 Oct;335(1):61-9.
[8] Bekker P, Ebsworth K, Walters MJ, et al. CCR9 Antagonists in the Treatment of Ulcerative Colitis. Mediators Inflamm. 2015;2015:628340.
Vercirnon是一种新型的、具有口服活性的CCR9趋化因子受体选择性拮抗剂，抑制CCR9介导的Molt-4细胞钙离子动员和趋化作用的IC₅₀值分别为5.4nM和3.4nM[1-2]。Vercirnon通过特异性阻断配体CCL25与表达在T细胞表面的受体CCR9结合，从而抑制T细胞向小肠黏膜的迁移和募集，可缓解炎症性肠病的炎症[3-4]。
在体外，Vercirnon（10nM）处理SACC-LM细胞48小时，Vercirnon显著抑制细胞增殖、迁移和侵袭能力，同时促进细胞凋亡[5]。Vercirnon（10nM）与CCL25（50nM）联合处理离体CD1小鼠胰岛1小时，Vercirnon显著诱导葡萄糖刺激胰岛素分泌，并促进cAMP的积累 [6]。
在体内，Vercirnon（10mg/kg或50mg/kg）每日两次皮下注射处理克罗恩病小鼠，连续10周。Vercirnon显著改善了与克罗恩病类似的肠道炎症[7]。Vercirnon（50mg/kg）每日两次皮下注射，用于处理mdr1a⁻/⁻小鼠，连续20周。Vercirnon显著改善了溃疡性结肠炎相关的体重减轻和结肠炎症[8]。
| Cell experiment [1]: | |
Cell lines | SACC-LM cells (human salivary adenoid cystic carcinoma cell line) and SACC-83 cells |
Preparation Method | SACC cells were maintained in Dulbecco's modified Eagle's medium/nutrient mixture F-12 (DMEM/F12) supplemented with 10% fetal bovine serum (FBS) and 1% penicillin-streptomycin at 37°C in a humidified atmosphere with 5% CO₂. For experiments, cells were treated with the CCR9 inhibitor Vercirnon at a concentration of 10nM, often following pre-treatment or co-treatment with 200ng/ml CCL25 for 24 or 48 hours. |
Reaction Conditions | 10nM; 24h or 48h |
Applications | Vercirnon significantly inhibited the CCL25/CCR9-induced activation of the PI3K/AKT signaling pathway, as evidenced by reduced phosphorylation levels of AKT (Ser473). |
| Animal experiment [2]: | |
Animal models | TNFΔARE/+ mice (a genetic model of Crohn's disease) |
Preparation Method | Female TNFΔARE/+ mice were administered Vercirnon (10mg/kg and 50mg/kg) or a vehicle control via subcutaneous injection twice per day, starting when the animals were 2 weeks old and continuing for 10 weeks. At the end of the study (when mice were 12 weeks old), animals were sacrificed, and intestinal tissues were dissected and processed for histological analysis. |
Dosage form | 10mg/kg and 50mg/kg; s.c.; Twice daily administration for 10 weeks. |
Applications | Treatment with Vercirnon resulted in a significant amelioration of intestinal inflammation. In the vehicle control group, 60% of mice developed severe/very severe inflammation. In contrast, Vercirnon treatment provided complete protection against severe inflammation. At the 50mg/kg dose of mice were histologically normal. This demonstrates that Vercirnon effectively blocks the development of pathology in a model of TNF-driven Crohn's disease. |
References: | |
| Cas No. | 698394-73-9 | SDF | |
| 别名 | 维塞诺; GSK-1605786; CCX282-B; Traficet-EN | ||
| 化学名 | N-[4-chloro-2-[(1-oxido-4-pyridinyl)carbonyl]phenyl]-4-(1,1-dimethylethyl)-benzenesulfonamide | ||
| Canonical SMILES | O=C(C(C=C1)=CC=[N]1=O)C(C=C(Cl)C=C2)=C2N[S](=O)(C3=CC=C(C(C)(C)C)C=C3)=O | ||
| 分子式 | C22H21ClN2O4S | 分子量 | 444.9 |
| 溶解度 | DMSO: 25 mg/ml | 储存条件 | Store at -20°C |
| General tips | 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；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.2477 mL | 11.2385 mL | 22.477 mL |
| 5 mM | 449.5 μL | 2.2477 mL | 4.4954 mL |
| 10 mM | 224.8 μL | 1.1238 mL | 2.2477 mL |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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2.
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