Enasidenib mesylate (AG-221 mesylate)
(Synonyms: 恩西地平甲磺酸盐; AG-221 mesylate) 目录号 : GC32904
An inhibitor of mutant IDH2
Cas No.:1650550-25-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Enasidenib is an inhibitor of mutant isocitrate dehydrogenase 2 (IDH2; IC50 = 0.1 ?M for IDH2 R140Q).1 It is selective for IDH2 R140Q over wild-type IDH2, wild-type IDH1, and IDH1 R132H (IC50s = 1.8, 0.45, and 48.4 ?M, respectively). Enasidenib (0.1, 1, and 5 ?M) inhibits production of D-2-hydroxyglutarate and induces differentiation in primary acute myeloid leukemia (AML) cells expressing IDH2 R140Q. It increases survival in a patient-derived xenograft (PDX) mouse model when administered at doses of 5, 15, and 45 mg/kg. Formulations containing enasidenib have been used in the treatment of AML.
1.Yen, K., Travins, J., Wang, F., et al.AG-221, a first-in-class therapy targeting acute myeloid leukemia harboring oncogenic IDH2 mutationsCancer Discov.7(5)478-493(2017)
| Cas No. | 1650550-25-6 | SDF | |
| 别名 | 恩西地平甲磺酸盐; AG-221 mesylate | ||
| Canonical SMILES | CS(=O)(O)=O.CC(O)(C)CNC1=NC(C2=NC(C(F)(F)F)=CC=C2)=NC(NC3=CC(C(F)(F)F)=NC=C3)=N1 | ||
| 分子式 | C20H21F6N7O4S | 分子量 | 569.48 |
| 溶解度 | DMSO : ≥ 100 mg/mL (175.60 mM) | 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 | 1.756 mL | 8.7799 mL | 17.5599 mL |
| 5 mM | 0.3512 mL | 1.756 mL | 3.512 mL |
| 10 mM | 0.1756 mL | 0.878 mL | 1.756 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。
Differentiation Syndrome Associated With Enasidenib, a Selective Inhibitor of Mutant Isocitrate Dehydrogenase 2: Analysis of a Phase 1/2 Study
JAMA Oncol 2018 Aug 1;4(8):1106-1110.PMID:29346478DOI:10.1001/jamaoncol.2017.4695.
Importance: Enasidenib mesylate, a mutant isocitrate dehydrogenase 2 (IDH2) protein inhibitor that promotes differentiation of leukemic myeloblasts, was recently approved by the US Food and Drug Administration for use in relapsed/refractory (R/R) mutant IDH2 acute myeloid leukemia (AML). During the first study of enasidenib in humans, a minority of patients with advanced myeloid neoplasms experienced unexpected signs/symptoms of a differentiation syndrome (DS), a potentially lethal entity. Objective: To characterize IDH-inhibitor-associated DS (IDH-DS) and its effective management. Design, setting, and participants: Using data obtained from a multicenter, open-label, pivotal phase 1/2 study of enasidenib, a differentiation syndrome review committee retrospectively evaluated potential cases of IDH-DS in enasidenib-treated patients with R/R AML. Data were collected between August 27, 2013, and October 14, 2016. The committee identified and agreed on signs and symptoms characteristic of IDH-DS and developed an algorithm for identification and treatment. Among 281 patients with R/R AML enrolled in the trial, the committee identified 72 patients for review based on investigator-reported cases of DS (n = 33) or reported adverse events or signs and symptoms characteristic of IDH-DS. Interventions: Treatment with enasidenib at a dosage of 50 to 650 mg/d was evaluated during the dose-escalation phase, and a dosage of 100 mg/d was used in the phase 1 expansion and phase 2, all in continual 28-day cycles. Main outcomes and measures: Unexpected adverse events of IDH-DS during the phase 1/2 study. Results: Thirty-three of the 281 patients (11.7%) were identified as having possible or probable IDH-DS. Median age of those 33 patients was 70 years (range, 38-80 years); 20 (60.6%) were male. The most frequent manifestations were dyspnea, fever, pulmonary infiltrates, and hypoxia. Median time to onset was 30 days (range, 7-129 days). Patients who experienced IDH-DS were less likely to have less than 20% bone marrow blasts (6% vs 22%, P = .04) and more likely to have undergone fewer previous anticancer regimens (median, 1.0 [range, 1-4] vs 2.0 [range, 1-14], P = .05) at study entry than those who did not. Thirteen patients (39.4%) had concomitant leukocytosis. Isocitrate dehydrogenase differentiation syndrome was effectively managed with systemic corticosteroids. The enasidenib regimen was interrupted for 15 patients (45.5%), but permanent discontinuation of treatment was not required. Conclusions and relevance: Isocitrate dehydrogenase differentiation syndrome is a recognizable and potentially lethal clinical entity, occurring in approximately 12% of enasidenib-treated patients with mutant-IDH2 R/R AML. It requires prompt recognition and management. As use of mutant IDH inhibitors increases, these findings and recommendations are increasingly germane to care of patients with mutant-IDH neoplasms. Trial registration: clinicaltrials.gov Identifier: NCT01915498.