| 规格 | 价格 | 库存 | 数量 |
|---|---|---|---|
| 10 mM * 1 mL in DMSO |
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| 1mg |
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| 2mg |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| 靶点 |
CCR9B ( IC50 = 2.6 nM ); CCR9A ( IC50 = 2.8 nM )
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|---|---|
| 体外研究 (In Vitro) |
Vercirnon (GSK-1605786) 抑制 CCR9 的原代细胞向 CCL25 趋化，IC50 为 6.8 nM。Vercirnon 抑制 CCL25 诱导的视黄酸 (RA) 培养人 T 细胞的趋化性。 Vercirnon 在 100% 人 AB 血清中中抑制RA培养细胞CCL25诱导的趋化性，IC50为141 nM。Vercirnon是一种有效的CCL25诱导的细胞趋化性适配器，IC50值分别为6.9 nM和1.3 nM[ 1]。
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| 体内研究 (In Vivo) |
Vercirnon (GSK-1605786) (10、50 mg/kg；sc；每天两次；从2周龄开始至12周龄)改善TNFΔARE模型中诱发炎症的严重程度[1]。 动物模型: C57BL /6 只小鼠（TNFΔARE 末端回肠炎小鼠模型）[1] 剂量：10, 50 mg/kg 给药方式：皮下注射；每天两次；从 2 周龄开始直至 12 周龄 结果：在 50 mg/kg 剂量下，可完全预防与 TNF 过度表达相关的严重炎症。较低剂量也有类似的保护作用。
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| 酶活实验 |
CCX282-B抑制了CCR9介导的Molt-4细胞上的钙（2+）动员和趋化性，IC（50）值分别为5.4和3.4 nM。在100%人血清存在的情况下，CCX282-B抑制了CCR9介导的趋化性，IC（50）为33 nM，添加α1-酸性糖蛋白不影响其效力。CCX282-B以6.8nM的IC（50）抑制了原代表达CCR9的细胞对CCL25的趋化性。CCX282-B是两种剪接形式的CCR9（CCR9A和CCR9B）的CCL25导向趋化性的等效抑制剂，IC（50）值分别为2.8和2.6 nM。CCX282-B还抑制了小鼠和大鼠CCR9介导的趋化性[1]。
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| 动物实验 |
C57BL/6 mice (TNFΔARE Mouse Model of Terminal Ileitis)
10, 50 mg/kg Subcutaneous; twice per day; starting at 2 weeks of age until 12 weeks of age mdr1a −/− Mouse Model of Ulcerative Colitis[2] All animal experiments and procedures were approved by the ChemoCentryx Institutional Animal Care and Use Committee under protocol number CCX-154-2002. Female mdr1a −/− and wild-type FVB mice were purchased from Taconic. CCX025, formulated in 1% hydroxypropyl methylcellulose, was dosed at 100 mg/kg s.c. once daily. CCX282-B, formulated in 5% Cremophor, was dosed at 50 mg/kg c.c. twice daily. During the course of the study, body weights and the incidence of diarrhea were recorded on a weekly basis. Any animals that exhibited weight loss of greater than 20% of their peak body weight were euthanized. Final body weights for any euthanized or dead animals were carried forward for data analysis. Diarrhea was scored on a 0–5 scale; when animals reached a score of ≥3, their diarrhea was constant and irreversible and was thus considered as established diarrhea. |
| 参考文献 | |
| 其他信息 |
Vercirnon is a novel, orally active anti-inflammatory agent that targets a chemokine receptor protein implicated in both Crohn's disease and ulcerative colitis, the two principal forms of IBD. It is under investigation in clinical trial NCT01611805 (Japanese Phase I of GSK1605786).
Mechanism of Action Vercirnon, a small molecule, orally-available drug, is intended to control the inappropriate immune system response underlying IBD by blocking the activity of the CCR9 chemokine receptor. In adults, CCR9 is a highly specific receptor expressed by T cells that migrate selectively to the digestive tract. The trafficking of T cells to the small and large intestine causes persistent inflammation that may result in Crohn's disease or ulcerative colitis - the two principal forms of IBD. |
| 分子式 |
C22H21CLN2O4S
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|---|---|
| 分子量 |
444.931143522263
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| 精确质量 |
444.091
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| 元素分析 |
C, 59.39; H, 4.76; Cl, 7.97; N, 6.30; O, 14.38; S, 7.21
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| CAS号 |
698394-73-9
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| 相关CAS号 |
Vercirnon sodium; 886214-18-2
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| PubChem CID |
10343454
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| 外观&性状 |
White to off-white solid powder
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| LogP |
6.251
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| tPSA |
97.08
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| 氢键供体(HBD)数目 |
1
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| 氢键受体(HBA)数目 |
5
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| 可旋转键数目(RBC) |
6
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| 重原子数目 |
30
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| 分子复杂度/Complexity |
687
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| 定义原子立体中心数目 |
0
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| SMILES |
O=S(C1=CC=C(C(C)(C)C)C=C1)(NC2=CC=C(Cl)C=C2C(C3=CC=[N+]([O-])C=C3)=O)=O
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| InChi Key |
JRWROCIMSDXGOZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H21ClN2O4S/c1-22(2,3)16-4-7-18(8-5-16)30(28,29)24-20-9-6-17(23)14-19(20)21(26)15-10-12-25(27)13-11-15/h4-14,24H,1-3H3
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| 化学名 |
4-tert-butyl-N-[4-chloro-2-(1-oxidopyridin-1-ium-4-carbonyl)phenyl]benzenesulfonamide
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| 别名 |
CCX282-B; Vercirnon; CCX282B; CCX 282B; 698394-73-9; Traficet-EN; GSK-1605786; CCX282-B; Verecimon; CCX-282-B; CCX-282b; GSK1605786; GSK 1605786; GSK-1605786
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| HS Tariff Code |
2934.99.9001
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| 存储方式 |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| 运输条件 |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| 溶解度 (体外实验) |
DMSO: ~45 mg/mL (~101.1 mM)
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|---|---|
| 溶解度 (体内实验) |
配方 1 中的溶解度: ≥ 2.5 mg/mL (5.62 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL 澄清 DMSO 储备液加入900 μL 玉米油中，混合均匀。 请根据您的实验动物和给药方式选择适当的溶解配方/方案： 1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液)); 2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方): 10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline); 假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL； 3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例; 4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶; 5、为保证最佳实验结果，工作液请现配现用！ 6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们; 7、 以上所有助溶剂都可在 Invivochem.cn网站购买。 |
| 制备储备液 | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2475 mL | 11.2377 mL | 22.4754 mL | |
| 5 mM | 0.4495 mL | 2.2475 mL | 4.4951 mL | |
| 10 mM | 0.2248 mL | 1.1238 mL | 2.2475 mL |
1、根据实验需要选择合适的溶剂配制储备液 (母液)：对于大多数产品，InvivoChem推荐用DMSO配置母液 (比如：5、10、20mM或者10、20、50 mg/mL浓度），个别水溶性高的产品可直接溶于水。产品在DMSO 、水或其他溶剂中的具体溶解度详见上”溶解度 (体外)”部分;
2、如果您找不到您想要的溶解度信息，或者很难将产品溶解在溶液中，请联系我们;
3、建议使用下列计算器进行相关计算（摩尔浓度计算器、稀释计算器、分子量计算器、重组计算器等）;
4、母液配好之后，将其分装到常规用量，并储存在-20°C或-80°C，尽量减少反复冻融循环。
计算结果:
工作液浓度： mg/mL；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL)。如该浓度超过该批次药物DMSO溶解度，请首先与我们联系。
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL ddH2O，混匀澄清。
(1) 请确保溶液澄清之后，再加入下一种溶剂 (助溶剂) 。可利用涡旋、超声或水浴加热等方法助溶；
(2) 一定要按顺序加入溶剂 (助溶剂) 。
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00540657 | Completed | Drug: CCX282-B Drug: Placebo |
Celiac Disease | ChemoCentryx | October 2007 | Phase 2 |
| NCT00306215 | Completed | Drug: CCX282-B | Crohn's Disease | ChemoCentryx | March 2006 | Phase 2 |
| NCT01277666 | Completed | Drug: GSK1605786A Drug: Placebo |
Crohn's Disease | GlaxoSmithKline | December 20, 2010 | Phase 3 |
| NCT00102921 | Completed | Drug: CCX282-B | Crohn Disease | ChemoCentryx | August 2004 | Phase 2 |
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