Vedolizumab
(Synonyms: 维多珠单抗; Anti-Human lymphocyte α4β7 integrin, Humanized Antibody) 目录号 : GC34211
Vedolizumab (anti-α4β7-integrin) is a humanized IgG1 monoclonal antibody that targets the α4β7 integrin for the treatment of ulcerative colitis and Crohn's disease.
Cas No.:943609-66-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
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Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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Kinase experiment: |
Vedolizumab inhibition of high-affinity binding of MAdCAM-1 to human peripheral blood memory CD4+ T lymphocytes is tested. Peripheral blood (90 μL) is incubated with a saturating concentration (3 μg/mL) of MAdCAM-1-murine-Fc fusion protein and 4 mM MnCl2 in a final volume of 100 μL for 1 h at room temperature, in the presence or absence of vedolizumab. After washing with assay buffer, the cells are stained with fluorescentlabeled anti-mouse IgG for 15 min at room temperature. After washing again, cells are incubated with mouse serum for 10 min at room temperature, followed by staining with anti-CD4 and anti-CD45RO antibodies for 15 min at room temperature. After washing, red blood cells are lysed with BD FACS lysing solution and analyzed by flow cytometry in a FACSCalibur with CellQuest Pro software[1]. |
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References: [1]. Soler D, et al. The binding specificity and selective antagonism of vedolizumab, an anti-alpha4beta7 integrintherapeutic antibody in development for inflammatory bowel diseases. J Pharmacol Exp Ther. 2009 Sep;330(3):864-75. |
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Vedolizumab (anti-α4β7-integrin) is a humanized IgG1 monoclonal antibody that targets the α4β7 integrin for the treatment of ulcerative colitis and Crohn's disease.
Vedolizumab (anti-α4β7-integrin) binds to a subset of human peripheral blood memory CD4+ T lymphocytes including gut-homing interleukin 17 T-helper lymphocytes at the highest level, also binds to eosinophils at high levels, and to naive T-helper lymphocytes, naive and memory cytotoxic T lymphocytes, B lymphocytes, natural killer cells, and basophils at lower levels; Vedolizumab binds to memory CD4+ T and B lymphocytes with subnanomolar potency with EC50 of 0.3-0.4 nM.[1]
[1] Soler D, et al. J Pharmacol Exp Ther. 2009 Sep;330(3):864-75.
| Cas No. | 943609-66-3 | SDF | |
| 别名 | 维多珠单抗; Anti-Human lymphocyte α4β7 integrin, Humanized Antibody | ||
| Canonical SMILES | [Vedolizumab] | ||
| 分子式 | 分子量 | 146814.9 | |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -80°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 | 0.0068 mL | 0.0341 mL | 0.0681 mL |
| 5 mM | 0.0014 mL | 0.0068 mL | 0.0136 mL |
| 10 mM | 0.0007 mL | 0.0034 mL | 0.0068 mL |
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| 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 |
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| % 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。
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Vedolizumab as induction and maintenance therapy for ulcerative colitis
N Engl J Med 2013 Aug 22;369(8):699-710.PMID:23964932DOI:10.1056/NEJMoa1215734.
Background: Gut-selective blockade of lymphocyte trafficking by Vedolizumab may constitute effective treatment for ulcerative colitis. Methods: We conducted two integrated randomized, double-blind, placebo-controlled trials of Vedolizumab in patients with active disease. In the trial of induction therapy, 374 patients (cohort 1) received Vedolizumab (at a dose of 300 mg) or placebo intravenously at weeks 0 and 2, and 521 patients (cohort 2) received open-label Vedolizumab at weeks 0 and 2, with disease evaluation at week 6. In the trial of maintenance therapy, patients in either cohort who had a response to Vedolizumab at week 6 were randomly assigned to continue receiving Vedolizumab every 8 or 4 weeks or to switch to placebo for up to 52 weeks. A response was defined as a reduction in the Mayo Clinic score (range, 0 to 12, with higher scores indicating more active disease) of at least 3 points and a decrease of at least 30% from baseline, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1. Results: Response rates at week 6 were 47.1% and 25.5% among patients in the Vedolizumab group and placebo group, respectively (difference with adjustment for stratification factors, 21.7 percentage points; 95% confidence interval [CI], 11.6 to 31.7; P<0.001). At week 52, 41.8% of patients who continued to receive Vedolizumab every 8 weeks and 44.8% of patients who continued to receive Vedolizumab every 4 weeks were in clinical remission (Mayo Clinic score ≤2 and no subscore >1), as compared with 15.9% of patients who switched to placebo (adjusted difference, 26.1 percentage points for Vedolizumab every 8 weeks vs. placebo [95% CI, 14.9 to 37.2; P<0.001] and 29.1 percentage points for Vedolizumab every 4 weeks vs. placebo [95% CI, 17.9 to 40.4; P<0.001]). The frequency of adverse events was similar in the Vedolizumab and placebo groups. Conclusions: Vedolizumab was more effective than placebo as induction and maintenance therapy for ulcerative colitis. (Funded by Millennium Pharmaceuticals; GEMINI 1 ClinicalTrials.gov number, NCT00783718.).
Long-term safety of Vedolizumab for inflammatory bowel disease
Aliment Pharmacol Ther 2020 Oct;52(8):1353-1365.PMID:32876349DOI:10.1111/apt.16060.
Background: Vedolizumab, a gut-selective α4 β7 integrin antibody, is approved for moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD). Aim: To report the final results from the Vedolizumab GEMINI long-term safety (LTS) study. Methods: The phase 3, open-label GEMINI LTS study (initiated May 2009) enrolled patients with UC or CD from four prior clinical trials and vedolizumab-naïve patients. Vedolizumab LTS was evaluated; efficacy and patient-reported outcomes were exploratory endpoints. Results: Enrolled patients (UC, n = 894; CD, n = 1349) received Vedolizumab 300 mg IV every 4 weeks; median cumulative exposure was 42.4 months (range: 0.03-112.2) for UC and 31.5 months (range: 0.03-100.3) for CD. Over 8 years, adverse events (AEs) occurred in 93% (UC) and 96% (CD) of patients, with UC (36%) and CD (35%) exacerbations most frequent. Serious AEs were reported for 31% (UC) and 41% (CD) of patients. Vedolizumab discontinuation due to AEs occurred in 15% (UC) and 17% (CD) of patients. There were no new trends for infections, malignancies, infusion-related reactions, or hepatic events, and no cases of progressive multifocal leukoencephalopathy. Of the ten deaths (UC, n = 4; CD, n = 6), two were considered drug-related by local investigators (West Nile virus infection-related encephalitis and hepatocellular carcinoma). Continuous Vedolizumab maintained clinical response long-term, with 33% (UC) and 28% (CD) of patients in clinical remission at 400 treatment weeks. Conclusions: The safety profile of Vedolizumab remains favourable with no unexpected or new safety concerns. These results further establish the safety of Vedolizumab and support its long-term use (NCT00790933/EudraCT 2008-002784-14).
Vedolizumab as induction and maintenance therapy for Crohn's disease
N Engl J Med 2013 Aug 22;369(8):711-21.PMID:23964933DOI:10.1056/NEJMoa1215739.
Background: The efficacy of Vedolizumab, an α4β7 integrin antibody, in Crohn's disease is unknown. Methods: In an integrated study with separate induction and maintenance trials, we assessed intravenous Vedolizumab therapy (300 mg) in adults with active Crohn's disease. In the induction trial, 368 patients were randomly assigned to receive Vedolizumab or placebo at weeks 0 and 2 (cohort 1), and 747 patients received open-label Vedolizumab at weeks 0 and 2 (cohort 2); disease status was assessed at week 6. In the maintenance trial, 461 patients who had had a response to Vedolizumab were randomly assigned to receive placebo or Vedolizumab every 8 or 4 weeks until week 52. Results: At week 6, a total of 14.5% of the patients in cohort 1 who received Vedolizumab and 6.8% who received placebo were in clinical remission (i.e., had a score on the Crohn's Disease Activity Index [CDAI] of ≤150, with scores ranging from 0 to approximately 600 and higher scores indicating greater disease activity) (P=0.02); a total of 31.4% and 25.7% of the patients, respectively, had a CDAI-100 response (≥100-point decrease in the CDAI score) (P=0.23). Among patients in cohorts 1 and 2 who had a response to induction therapy, 39.0% and 36.4% of those assigned to Vedolizumab every 8 weeks and every 4 weeks, respectively, were in clinical remission at week 52, as compared with 21.6% assigned to placebo (P<0.001 and P=0.004 for the two Vedolizumab groups, respectively, vs. placebo). Antibodies against Vedolizumab developed in 4.0% of the patients. Nasopharyngitis occurred more frequently, and headache and abdominal pain less frequently, in patients receiving Vedolizumab than in patients receiving placebo. Vedolizumab, as compared with placebo, was associated with a higher rate of serious adverse events (24.4% vs. 15.3%), infections (44.1% vs. 40.2%), and serious infections (5.5% vs. 3.0%). Conclusions: Vedolizumab-treated patients with active Crohn's disease were more likely than patients receiving placebo to have a remission, but not a CDAI-100 response, at week 6; patients with a response to induction therapy who continued to receive Vedolizumab (rather than switching to placebo) were more likely to be in remission at week 52. Adverse events were more common with Vedolizumab. (Funded by Millennium Pharmaceuticals; GEMINI 2 ClinicalTrials.gov number, NCT00783692.).
Safety of New Biologics (Vedolizumab and Ustekinumab) and Small Molecules (Tofacitinib) During Pregnancy: A Review
Drugs 2020 Jul;80(11):1085-1100.PMID:32562207DOI:10.1007/s40265-020-01346-4.
Two new biological drugs (Vedolizumab and ustekinumab) and one small molecule (tofacitinib) have been recently approved for the treatment of inflammatory bowel disease. Therefore, we must be familiar with the safety of these "new" drugs during pregnancy and breastfeeding. In the present article, we critically review available data on the safety of new biologics (Vedolizumab and ustekinumab) and small molecules (tofacitinib) during pregnancy and breastfeeding, with special focus on women with inflammatory bowel disease. Bibliographical searches (MEDLINE) up to April 2020 were performed. The timing and mechanisms of placental transfer of Vedolizumab and ustekinumab are expected to be similar to anti-TNF agents. Animal studies show no evidence of adverse effects on pre- or post-natal development after administration of Vedolizumab and ustekinumab. Just a few studies including patients treated with Vedolizumab or ustekinumab during pregnancy have been published, reporting uneventful pregnancies in most cases. The clinical programme of both drugs and post-marketing studies showed no new safety concerns. Due to the expected safety of Vedolizumab and ustekinumab during pregnancy, it may be recommended to plan the final pregnancy dose approximately 8 or 12 weeks, respectively, before the estimated date of delivery. Live vaccines should be avoided for up to a year in children exposed in utero to Vedolizumab or ustekinumab unless drug elimination has been documented. Miniscule amounts of Vedolizumab and ustekinumab are transferred to breast milk, so breastfeeding is probably safe. There is no evidence of adverse effect of Vedolizumab or ustekinumab paternal exposure. Regarding tofacitinib, it is reasonable to assume that this molecule crosses the placenta from the beginning of pregnancy. In animal studies, tofacitinib was feticidal and teratogenic in rats and rabbits, although at exposures many times greater than the standard human dose. Reported outcomes of pregnancy cases identified from tofacitinib randomised controlled trials, post-approval and non-interventional studies, and spontaneous adverse-event reporting appear similar to those observed in the general population. Nevertheless, at present, the use of tofacitinib during pregnancy should be avoided. Although no human studies have reported outcomes of breastfeeding with small molecules such as tofacitinib, this drug is present in lactating rat milk so, at present, breastfeeding should be avoided. Pregnancy among patients with paternal exposure to tofacitinib appears to be safe. In summary, we can conclude that new biologic agents (Vedolizumab and ustekinumab) and small molecules (tofacitinib) should be used during pregnancy only if the benefits to the mother outweigh the risks to the mother and unborn child.
Efficacy and Safety of Vedolizumab Subcutaneous Formulation in a Randomized Trial of Patients With Ulcerative Colitis
Gastroenterology 2020 Feb;158(3):562-572.e12.PMID:31470005DOI:10.1053/j.gastro.2019.08.027.
Background & aims: Maintenance treatment with Vedolizumab, a monoclonal antibody that inhibits the gut-selective α4β7 integrin, is administered intravenously. Some patients might prefer a subcutaneous formulation of Vedolizumab for maintenance treatment. Subcutaneous Vedolizumab was investigated as maintenance treatment in patients with moderately to severely active ulcerative colitis. Methods: We performed a phase 3, double-blind, double-dummy trial at 141 sites in 29 countries from December 18, 2015 through August 21, 2018. Patients with moderately to severely active ulcerative colitis received open-label treatment with intravenous Vedolizumab 300 mg at weeks 0 and 2. At week 6, patients with clinical response were randomly assigned maintenance treatment with subcutaneous Vedolizumab 108 mg every 2 weeks, intravenous Vedolizumab 300 mg every 8 weeks, or placebo. The primary end point was clinical remission at week 52, which was defined as a total Mayo score of ≤2 and no subscore >1. Results: Among the randomized 216 patients, clinical remission at week 52 was achieved by 46.2%, 42.6%, and 14.3% of patients in the subcutaneous Vedolizumab, intravenous Vedolizumab, and placebo groups, respectively (subcutaneous Vedolizumab vs placebo: Δ32.3%; 95% confidence interval, 19.7%-45.0%; P < .001). The subcutaneous Vedolizumab group also had greater endoscopic improvement and durable clinical response at week 52 compared with placebo (both P < .001). The incidence of injection-site reactions was more frequent in patients given subcutaneous Vedolizumab (10.4%) than intravenous Vedolizumab (1.9%) or placebo (0%); these were not treatment limiting, most were mild, and none resulted in discontinuation. Subcutaneous and intravenous Vedolizumab safety profiles were otherwise similar. Conclusions: Subcutaneous Vedolizumab is effective as maintenance therapy in patients with moderately to severely active ulcerative colitis who had a clinical response to intravenous Vedolizumab induction therapy. It has a favorable safety and tolerability profile. ClinicalTrials.gov ID: NCT02611830; EudraCT 2015-000480-14.