Eldelumab
(Synonyms: BMS-936557; MDX-1100) 目录号 : GC66332
Eldelumab (BMS-936557) 是一种人源化抗 CXCL10 (IP-10) 单克隆抗体 (IgG1型)。Eldelumab 可选择性地与 CXCL10 结合，并阻断 CXCL10 诱导的钙通量和细胞迁移。Eldelumab 可用于自身免疫和自身炎症性疾病 (如类风湿性关节炎、溃疡性结肠炎和克罗恩病) 的研究。
Cas No.:946414-98-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Eldelumab (BMS-936557) is a humanised anti-CXCL10 (IP-10) monoclonal antibody (IgG1 type). Eldelumab selectively binds to CXCL10 and blocks CXCL10-induced calcium flux and cell migration. Eldelumab can be used in studies of autoimmune and auto-inflammatory diseases such as rheumatoid arthritis, ulcerative colitis and crohn's disease[1][2].
| Cas No. | 946414-98-8 | SDF | Download SDF |
| 别名 | BMS-936557; MDX-1100 | ||
| 分子式 | 分子量 | ||
| 溶解度 | 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。 | ||
| 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。
Eldelumab [Anti-IP-10] Induction Therapy for Ulcerative Colitis: A Randomised, Placebo-Controlled, Phase 2b Study
J Crohns Colitis 2016 Apr;10(4):418-28.PMID:26721935DOI:10.1093/ecco-jcc/jjv224.
Background and aims: Interferon-γ-inducible protein-10 [IP-10] mediates immune cell trafficking from the circulation to the inflamed colon and decreases gut epithelial cell survival. IP-10 expression is increased in patients with ulcerative colitis [UC]. We report efficacy and safety results from a dose-ranging induction study of Eldelumab, a fully human monoclonal antibody to IP-10, in moderately to severely active UC. Methods: A total of 252 adults with UC [Mayo score ≥ 6 and endoscopic subscore ≥ 2] were randomised 1:1:1 to placebo or Eldelumab 15 or 25 mg/kg administered intravenously on Days 1 and 8 and every other week thereafter. The primary endpoint was clinical remission [Mayo score ≤ 2; no individual subscale score > 1] at Week 11. Key secondary endpoints included Mayo score clinical response and mucosal healing at Week 11. Results: Neither Eldelumab 15 or 25 mg/kg resulted in significant increases vs placebo in the proportion of patients achieving Week 11 clinical remission. Remission and response rates were 17.6% and 47.1% with Eldelumab 25mg/kg, 13.1% and 44.0% with Eldelumab 15mg/kg, and 9.6% and 31.3% with placebo. Clinical remission and response rates were higher in anti-tumour necrosis factor [TNF]-naïve patients treated with Eldelumab compared with placebo. Eldelumab treatment was well tolerated and no immunogenicity was observed. Conclusions: The primary endpoint was not achieved with induction treatment with Eldelumab 15 or 25 mg/kg in patients with UC. Trends towards clinical remission and response were observed in the overall population and were more pronounced in anti-TNF naïve patients. Eldelumab safety signals were consistent with those reported previously [ClinicalTrials.gov number, NCT01294410].
Eldelumab [anti-interferon-γ-inducible protein-10 antibody] Induction Therapy for Active Crohn's Disease: a Randomised, Double-blind, Placebo-controlled Phase IIa Study
J Crohns Colitis 2017 Jul 1;11(7):811-819.PMID:28333187DOI:10.1093/ecco-jcc/jjx005.
Background and aims: This 11-week Phase IIa induction study evaluated the efficacy and safety of Eldelumab in patients with active Crohn's disease. Methods: Adults with Crohn's Disease Activity Index 220-450 were randomised 1:1:1 to placebo or Eldelumab 10 or 20 mg/kg intravenously on Days 1 and 8, and alternate weeks thereafter. All patients underwent ileocolonoscopy at baseline. Patients with active inflammation according to the Simplified Endoscopic Score for Crohn's Disease criteria [the originally planned endoscopy cohort] underwent another ileocolonoscopy at Week 11 at the investigator's discretion. All ileocolonoscopies were centrally read. The primary objective was identification of the Eldelumab target exposure for induction of remission [absolute Crohn's Disease Activity Index score < 150]. Rates of clinical response [reduction of ≥ 100 from baseline or absolute score < 150 Crohn's Disease Activity Index], remission, and endoscopic improvements were also assessed. Results: A total of 121 patients were randomised. The Eldelumab exposure-remission relationship was not significant at Week 11. Numerically higher remission and response rates were reported with Eldelumab 20 mg/kg [29.3% and 41.5%, respectively] and 10 mg/kg [22.5% and 47.5%] versus placebo [20.0% and 35.0%]. A higher proportion of patients with a baseline Simplified Endoscopic Score for Crohn's Disease > 2 who received Eldelumab achieved a 50% improvement in score and greater reductions from baseline endoscopy scores overall versus placebo. Adverse events were comparable across treatment groups. Conclusions: No exposure-remission relationship was seen with Eldelumab. Eldelumab induction treatment demonstrated trends towards clinical and endoscopic efficacy. Safety was consistent with that reported previously. ClinicalTrials.gov identifier: NCT01466374.
Development of drugs to target interactions between leukocytes and endothelial cells and treatment algorithms for inflammatory bowel diseases
Gastroenterology 2014 Nov;147(5):981-9.PMID:25220794DOI:10.1053/j.gastro.2014.08.044.
Increased understanding of the pathogenesis of inflammatory bowel diseases (IBDs) has led to new therapeutic strategies. One of these is to target the molecules that regulate interactions between leukocytes and endothelial cells at sites of inflammation (mainly leukocyte integrins and endothelial cell adhesion molecules of the immunoglobulin superfamily). These molecules have been validated as therapeutic targets for IBD; several have shown efficacy, and 2 have been approved by the Food and Drug Administration for treatment of IBD. Natalizumab, the first anti-integrin antibody tested for treatment of IBD, blocks the α4 subunit. Although it is effective, its clinical use has been limited by its association with risk of progressive multifocal leukoencephalopathy. Other, allegedly more selective drugs that affect leukocyte recruitment in the gastrointestinal tract have been developed or are under investigation and could increase safety. These include vedolizumab and AMG 181 (antibodies against α4β7), etrolizumab (anti-β7), and PF-00547659 (anti-mucosal vascular addressin cell adhesion molecule 1). Other agents have been developed to block α4 (the small molecule AJM300), CCR9 (the small molecule CCX282-B), and CXCL10 (the antibody Eldelumab). We review the scientific rationale for inhibiting interactions between leukocytes and endothelial cells to reduce intestinal inflammation and analyze the clinical studies that have been performed to test these new molecules, with particular attention to safety. We propose an evidence-based clinical positioning of this class of drugs.
Response to Placebo, Measured by Endoscopic Evaluation of Crohn's Disease Activity, in a Pooled Analysis of Data From 5 Randomized Controlled Induction Trials
Clin Gastroenterol Hepatol 2020 May;18(5):1121-1132.e2.PMID:31442599DOI:10.1016/j.cgh.2019.08.025.
Background & aims: Endoscopy is used to measure activity of Crohn's disease (CD) and determine eligibility and outcomes of participants in randomized controlled trials of therapeutic agents. We aimed to estimate the rate of response to placebo in trials, based on endoscopic evaluation of CD activity, and identify factors that affect this response. Methods: We collected patient-level data from randomized, double-blind, placebo-controlled trials of therapeutic agents for CD that included centrally-read endoscopic assessments with validated scoring indices. We analyzed data from induction trials of Eldelumab, filgotinib, risankizumab, and ustekinumab (from 188 patients given placebo). The primary outcome was the rate of response to placebo, based on endoscopic assessment of CD activity (>50% reduction in the simple endoscopic score for CD). Rate of remission, based on endoscopic score, was a secondary outcome. Overall rates of response to placebo were calculated using the inverse variance-weighted average method and presented with 95% CIs. We performed a multi-variable meta-regression analysis to identify determinants of response to placebo, assessed endoscopically, using patient-level data from the filgotinib and ustekinumab trials. Results: The pooled rate of response among patients given placebo was 16.2% (95% CI, 10.5%-22.0%) and the rate of remission in this group was 5.2% (95% CI, 1.7%-8.8%). Prior exposure to tumor necrosis factor antagonists (odds ratio, 0.31; 95% CI, 0.10-0.93; P = .036) and increased concentration of C-reactive protein at baseline (odds ratio, 0.93; 95% CI, 0.87-0.98; P = .014 per 10 mg/L increase) were independently associated with lower rates of response to placebo. Conclusions: Rates of response and remission to placebo, determined by centrally-read endoscopy, in induction trials of therapies for CD are low. These estimates are important for sample size calculations for randomized placebo-controlled trials that use the Simple Endoscopic Score for CD as an endpoint. They also provide a benchmark to interpret findings from non-placebo controlled, prospective, randomized, unblinded trials.