MLN3126
目录号 : GC65990
MLN3126 是一种具有口服活性的强效 CCR9 拮抗剂。 MLN3126 抑制 CCL25 诱导的钙动员 (calcium mobilization) 和小鼠初级胸腺细胞趋化 (chemotaxis)，抑制钙内流的 IC50 为 6.3 nM。
Cas No.:628300-71-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
MLN3126 is an orally active and potent CCR9 antagonist. MLN3126 inhibits CCL25-induced calcium mobilization and chemotaxis of mouse primary thymocytes, wiht an IC50 value of 6.3 nM for calcium influx[1].
MLN3126 inhibits CCL25-induced calcium mobilization with an IC50 value of 6.3 nM in CCR9 expressing cells[1].
MLN3126 inhibits the binding of biotinylated CCL25 to CCR9 with an IC50 of 14.2 nM[1].
Cell Invasion Assay[1]
| Cell Line: | Mouse thymocytes |
| Concentration: | 0.01, 0.03, 0.1, 0.3, 1, 3 μM |
| Incubation Time: | 90 min |
| Result: | Inhibited CCL25-induced chemotaxis of mouse thymocytes. |
MLN3126 (2.5% w/w; p.o.) decreases colonic level of IFN-γ, largely produced by T cells[1].
MLN3126 (0.05, 0.25 and 1% (w/w); p.o.) has the potential activity for alleviating inflammatory bowel disease (IBD)[1].
| Animal Model: | Activated T cell transferred colitis mouse model[1] |
| Dosage: | 0.05, 0.25 and 1% (w/w) (around 4 g/day) |
| Administration: | Oral gavage; 21 days |
| Result: | Blocked CCR9/CCL25 interaction by inhibiting migration of T cells to the colon and resulted in the amelioration of colitis. |
| Cas No. | 628300-71-0 | SDF | Download SDF |
| 分子式 | C21H19ClN2O5S | 分子量 | 446.9 |
| 溶解度 | DMSO : 25 mg/mL (55.94 mM; ultrasonic and warming and heat to 60°C) | 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 | 2.2376 mL | 11.1882 mL | 22.3764 mL |
| 5 mM | 0.4475 mL | 2.2376 mL | 4.4753 mL |
| 10 mM | 0.2238 mL | 1.1188 mL | 2.2376 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
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，
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 saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
MLN3126, an antagonist of the chemokine receptor CCR9, ameliorates inflammation in a T cell mediated mouse colitis model
Int Immunopharmacol 2018 Jul;60:160-169.PMID:29730559DOI:10.1016/j.intimp.2018.04.049.
C-C chemokine receptor 9 (CCR9) is the homing receptor for C-C motif chemokine ligand 25 (CCL25), and contributes to the maintenance of mucosal immunity and pathogenesis of inflammatory bowel disease (IBD) through the recruitment of T cells into the gut mucosa. Recent reports suggest that the interaction of CCR9 and CCL25 in the large intestine correlate with disease severity of colonic IBD. MLN3126 is an orally available small molecular compound with potent and selective CCR9 antagonist activity. MLN3126 inhibited CCL25-induced calcium mobilization in human CCR9 transfected cells and CCL25-induced chemotaxis of mouse primary thymocytes in a dose-dependent manner. The potential effect of MLN3126 in an activated T cell transfer mouse colitis model was compared with that of an anti-tumor necrosis factor (TNF)-α antibody. CCL25 protein was detected in the colon of mucosal epithelial cells and CCR9+ CD4+ T cells were observed in the lamina propria of the colon of mice with colitis. Dietary administration of MLN3126 to the mice maintained sufficient concentration of the compound in the plasma and dose-dependently inhibited progression of colitis compared to the vehicle control group. Anti-TNF-α antibody, a surrogate for a standard of care for IBD treatment, was also efficacious in the colitis model. These results suggest that MLN3126 would be a promising orally available CCR9 antagonist to treat colonic IBD.
Mechanism for Covalent Binding of MLN3126, an Oral Chemokine C-C Motif Receptor 9 Antagonist, to Serum Albumins
Drug Metab Dispos 2018 Mar;46(3):204-213.PMID:29269409DOI:10.1124/dmd.117.078782.
N-{4-Chloro-2-[(1-oxidopyridin-4-yl)carbonyl]phenyl}-4-(propan-2-yloxy)benzenesulfonamide (MLN3126) is an orally available chemokine C-C motif receptor 9 selective antagonist. In nonclinical pharmacokinetic studies of MLN3126, nonextractable radioactivity was observed in plasma after oral administration of 14C-labeled MLN3126 ([14C]MLN3126) to Sprague-Dawley (SD) rats. In this study, the nonextractable radioactive component was digested with trypsin or a nonspecific protease, pronase, after chemical reduction to obtain drug-peptide adducts or drug-amino acid adducts. The chemical structure of these adducts was characterized by liquid chromatography/mass spectrometry. The results demonstrated that the major part of the nonextractable radioactivity was accounted for by covalent binding via the Schiff base formed specifically between the ε-amino group of lysine residue 199 in rat serum albumin and the carbonyl group of MLN3126. The half-life (t1/2) of the total radioactivity in plasma during and after 21 daily multiple oral administrations of [14C]MLN3126 to SD rats was approximately 5-fold shorter than the reported t1/2 of albumin in rats. The data indicated that the covalent binding was reversible under physiologic conditions. The formation of the covalent binding was also confirmed in in vitro incubations with serum albumins from rats, humans, and dogs in the same manner, indicating that there are no qualitative interspecies differences in the formation of the Schiff base.