Ixazomib citrate
(Synonyms: 枸橼酸艾沙佐米; MLN9708) 目录号 : GC36356
Ixazomib citrate (MLN9708, Ninlaro) is a prodrug of Ixazomib (MLN2238), which is a selective, orally bioavailable inhibitor of 20S proteasome that inhibits the chymotrypsin-like proteolytic (β5) site with IC50 of 3.4 nM and Ki of 0.93 nM, respectively. Ixazomib (MLN2238) also inhibits caspase-like (β1) and trypsin-like (β2) proteolytic sites with IC50 of 31 nM and 3500 nM, respectively.
Cas No.:1239908-20-3
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
Ixazomib citrate (MLN9708, Ninlaro) is a prodrug of Ixazomib (MLN2238), which is a selective, orally bioavailable inhibitor of 20S proteasome that inhibits the chymotrypsin-like proteolytic (β5) site with IC50 of 3.4 nM and Ki of 0.93 nM, respectively. Ixazomib (MLN2238) also inhibits caspase-like (β1) and trypsin-like (β2) proteolytic sites with IC50 of 31 nM and 3500 nM, respectively.
[1] Erik Kupperman, et al. Cancer Res. 2010 Mar 1;70(5):1970-80. [2] Edmund C Lee, et al. Clin Cancer Res . 2011 Dec 1;17(23):7313-23. [3] Gregory T.Notte. Annual Reports in Medicinal Chemistry. Volume 48, 2013, Pages 451-469.
| Cas No. | 1239908-20-3 | SDF | |
| 别名 | 枸橼酸艾沙佐米; MLN9708 | ||
| Canonical SMILES | O=C(O)CC1(CC(O)=O)OB([C@@H](NC(CNC(C2=CC(Cl)=CC=C2Cl)=O)=O)CC(C)C)OC1=O | ||
| 分子式 | C20H23BCl2N2O9 | 分子量 | 517.12 |
| 溶解度 | DMSO: ≥ 100 mg/mL (193.38 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 | 1.9338 mL | 9.6689 mL | 19.3379 mL |
| 5 mM | 0.3868 mL | 1.9338 mL | 3.8676 mL |
| 10 mM | 0.1934 mL | 0.9669 mL | 1.9338 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。
Pharmacokinetic drug evaluation of Ixazomib citrate for the treatment of multiple myeloma
Expert Opin Drug Metab Toxicol 2018 Jan;14(1):91-99.PMID:29235380DOI:10.1080/17425255.2018.1417388.
multiple myeloma (MM) is a plasma cell disorder that represents the second most frequent hematologic cancer. Although MM is still an incurable disease, prognosis has improved in the last decades thanks to the introduction of novel agents such as proteasome inhibitors (PIs), immunomodulatory drugs, monoclonal antibodies, and histone deacetylase inhibitors. Areas covered: ixazomib is the first oral PI recently approved by Food and Drug Administration (FDA) and European Medicine Agency (EMA) in combination with lenalidomide and dexamethasone as salvage therapy in MM patients. In this paper, we focus on its pharmacokinetics features, as well as its safety and efficacy in clinical studies. Expert opinion: ixazomib can be considered an oral analogue of bortezomib, with 9.5-day half-life, 58% of oral bioavailability, and a large distribution volume of 543L. These features make it a versatile molecule, potentially useful both in combination and as single agent. Oral route of administration and good efficacy/safety profile are its winning characteristics, providing the rationale for a future role also in the maintenance setting.
An evidence-based review of Ixazomib citrate and its potential in the treatment of newly diagnosed multiple myeloma
Onco Targets Ther 2014 Sep 29;7:1793-800.PMID:25302026DOI:10.2147/OTT.S49187.
Proteasome inhibition represents one of the more important therapeutic targets in the treatment of multiple myeloma (MM), since by suppressing nuclear factor-κB activity, which promotes myelomagenesis, it makes plasma cells susceptible to proapoptotic signals. Bortezomib, the first proteasome inhibitor approved for MM therapy, has been shown to increase response rate and improve outcome in patients with relapsed/refractory disease and in the frontline setting, particularly when combined with immunomodulatory drugs and alkylating agents. Among second-generation proteasome inhibitors, ixazomib (MLN9708) is the first oral compound to be evaluated for the treatment of MM. Ixazomib has shown improved pharmacokinetic and pharmacodynamic parameters compared with bortezomib, in addition to similar efficacy in the control of myeloma growth and prevention of bone loss. Ixazomib was found to overcome bortezomib resistance and to trigger synergistic antimyeloma activity with dexamethasone, lenalidomide, and histone deacetylase inhibitors. Phase I/II studies using ixazomib weekly or twice weekly in relapsed/refractory MM patients suggested antitumor activity of the single agent, but more promising results have been obtained with the combination of ixazomib, lenalidomide, and dexamethasone in newly diagnosed MM. Ixazomib has also been used in systemic amyloidosis as a single agent, showing important activity in this difficult-to-treat plasma-cell dyscrasia. More frequent side effects observed during administration of ixazomib were thrombocytopenia, nausea, vomiting, diarrhea, fatigue, and rash, whereas severe peripheral neuropathy was rare. Here, we review the chemical characteristics of ixazomib, as well as its mechanism of action and results from preclinical and clinical trials.
The investigational proteasome inhibitor ixazomib for the treatment of multiple myeloma
Future Oncol 2015;11(8):1153-68.PMID:25832873DOI:10.2217/fon.15.9.
Ixazomib is an investigational, reversible 20S proteasome inhibitor. It is the first oral proteasome inhibitor under clinical investigation in multiple myeloma (MM). Under physiological conditions, the stable citrate ester drug substance, Ixazomib citrate (MLN9708), rapidly hydrolyzes to the biologically active boronic acid, ixazomib (MLN2238). Preclinical studies have demonstrated antitumor activity in MM cell lines and xenograft models. In Phase I/II clinical studies ixazomib has had generally manageable toxicities, with limited peripheral neuropathy observed to date. Preliminary data from these studies indicate ixazomib is active as a single agent in relapsed/refractory MM and as part of combination regimens in newly diagnosed patients. Phase III studies in combination with lenalidomide-dexamethasone are ongoing.
PEG@ Carbon Nanotubes Composite as an Effective Nanocarrier of Ixazomib for Myeloma Cancer Therapy
Nanoscale Res Lett 2022 Aug 5;17(1):72.PMID:35930196DOI:10.1186/s11671-022-03707-2.
In this work, the preparation of a PEG@ multi-walled carbon nanotubes (MWCNTs) composite has shown a great potential effect in tumor therapy using graphite powder at room temperature. PEGylated MWCNTs were created and used as a carrier for targeting the antineoplastic drug Ixazomib to myeloma cancer cells (abnormal plasma cells). Ixazomib (MLN2238) was covalently encapsulated into functionalized carbon nanotubes modified with polyethylene glycol (PEG 600) to obtain MWCNTs-PEG-MLN2238. The Ixazomib@ MWCNTs-PEG composite shows promising results as an effective nanocarrier and using a small amount of MWCNTs-PEG-Ixazomib that has a low toxicity compared with that of Ixazomib alone. A multifunctional MWCNTs-PEG-Ixazomib composite is used to test biological effects on multiple myeloma cell lines RPMI 8226 using the MTT assay to enhance treatment efficiency. The cytotoxicity of free Ixazomib citrate (69% cell viability of RPMI8226 cells) was higher than that of MWCNTs-PEG-Ixazomib (91% cell viability) at the same maximum concentration of Ixazomib citrate (50 µg/ml). In this work, we performed a study of preparation of MWCNTs with an acceptable Ixazomib loading efficiency and determination of the drug systemic toxicity for the first time. In this study, the preparation of MWCNTs with acceptable Ixazomib loading efficiency and determination of the drug systemic toxicity was performed for the first time. The MTT assay results show decreasing the toxicity of Ixazomib after loading with the MWCNTs-PEG composite. The MWCNTs-PEG @ Ixazomib show promising results as an effective carrier of Ixazomib and lead to a decrease in the cost of using Ixazomib.
A phase 0 analysis of ixazomib in patients with glioblastoma
Mol Clin Oncol 2020 Nov;13(5):43.PMID:32874573DOI:10.3892/mco.2020.2114.
Improving overall survival in recurrent glioblastoma remains a challenge, and drugs acting by unique mechanisms are urgently required. Ixazomib is an orally-administered proteasome inhibitor used in combination with lenalidomide and dexamethasone to treat patients with multiple myeloma who have received at least one prior therapy. However, ixazomib's ability to reach brain tumors has not been studied during its development. The aim of the present study (ClinicalTrials.gov, NCT02630030) was to establish and quantify ixazomib's presence in glioblastoma. The present study investigated 3 patients with recurrent glioblastoma after administration of oral Ixazomib citrate (MLN 9708) at a fixed 4.0 mg dose within a 3-hpreoperative window. A total of 2 blood samples were taken from each patient at the time of incision, tumor sampling and closure. Brain tumor samples were collected during tumor resection. These samples were then used to measure the plasma and brain tumor tissue concentration of the biologically-active form of ixazomib (MLN 2238). Patient 1 had plasma concentrations of ixazomib averaging 26.2, 21.8 and 15.3 ng/ml at incision, tumor sampling and closure, respectively. The brain tumor tissue concentration was 7.88 ng/g. Patient 2 had the same interval and brain tumor tissue measurements of 19.0, 18.0 and 8.93 ng/ml, and 2.03 ng/g. Patient 3 had plasma concentration interval measurements of 25.6, 36.2 and 28.7 ng/ml. Multiple brain tumor tissue samples were taken in patient 3, with an average tissue ixazomib concentration of 3.37 ng/g. Ixazomib was found at plasma concentrations commensurate with its previously established pharmacokinetic profile without clinically relevant drug-related adverse events. Ixazomib reaches glioblastoma tissues at measurable concentrations at the time of tumor resection, confirming target tissue delivery. This justifies the phase I study of ixazomib in recurrent glioblastoma currently in development.