WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H205541
CAS#: 1239908-20-3 (citrate)
Description: Ixazomib citrate, also known as MLN9708, is a prodrug of Ixazomib (MMLN-2238). MLN9708 is an orally bioavailable second generation proteasome inhibitor (PI) with potential antineoplastic activity. MLN9708, after hydrolyzing to pharmacologically active MLN2238 (ixazomib), is a next-generation proteasome inhibitor with demonstrated preclinical and clinical antimyeloma activity. MLN9708, compared with bortezomib, has improved pharmacokinetics, pharmacodynamics, and antitumor activity in preclinical studies.
Hodoodo Cat#: H205541
Name: Ixazomib citrate
CAS#: 1239908-20-3 (citrate)
Chemical Formula: C20H23BCl2N2O9
Exact Mass: 516.09
Molecular Weight: 517.122
Elemental Analysis: C, 46.45; H, 4.48; B, 2.09; Cl, 13.71; N, 5.42; O, 27.85
Related CAS #: 1072833-77-2 (free) 1239908-20-3 (citrate) 1201902-80-8 2026591-78-4 (EtOH) 2026591-78-4 (i-PrOH)
Synonym: MLN9708; MLN-9708; MLN 9708; ixazomib citrate. MMLN-2238-prodrug. MMLN 2238-prodrug; MMLN2238-prodrug; Ixazomib-prodrug; Ninlaro.
IUPAC/Chemical Name: (R)-2,2'-(2-(1-(2-(2,5-Dichlorobenzamido)acetamido)-3-methylbutyl)-5-oxo-1,3,2-dioxaborolane-4,4-diyl)diacetic acid
InChi Key: MBOMYENWWXQSNW-AWEZNQCLSA-N
InChi Code: InChI=1S/C20H23BCl2N2O9/c1-10(2)5-14(21-33-19(32)20(34-21,7-16(27)28)8-17(29)30)25-15(26)9-24-18(31)12-6-11(22)3-4-13(12)23/h3-4,6,10,14H,5,7-9H2,1-2H3,(H,24,31)(H,25,26)(H,27,28)(H,29,30)/t14-/m0/s1
SMILES Code: O=C1C(CC(O)=O)(CC(O)=O)OB([C@@H](NC(CNC(C2=CC(Cl)=CC=C2Cl)=O)=O)CC(C)C)O1
Appearance: White to off-white solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: soluble in DMSO, not soluble in water.
Shelf Life: >5 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info: Please note: Some vendors mistakenly list the name of this product - MLN9708 - as Ixazomib. MLN9708 is a PRODRUG of Ixazomib. MLN9708 is not the same as Ixazomib. Ixazomib, also known as MLN-2238, it's CAS# is 1072833-77-2, please see our website: http://www.hodoodo.com/products/5649
| Biological target: | Ixazomib citrate (MLN9708) is a reversible inhibitor of the chymotrypsin-like proteolytic β5 site of the 20S proteasome with an IC50 of 3.4 nM and a Ki of 0.93 nM. |
| In vitro activity: | To further examine the molecular mechanism through which ixazomib blocks cell proliferation, the effects of the drug on mitosis- and apoptosis-related genes was investigated. As shown in Fig. 4, ixazomib decreased the protein levels of cyclin E1, cyclin D1, and Bcl-2 in RPMI-8226 and U-266 cells. The reduction of cyclin E1, cyclin D1 and Bcl-2 protein levels by ixazomib was relieved by UBE2K transfection. Alternatively, ixazomib increased the protein levels of cyclin B1, McL-1, and PARP1 in cells, while UBE2K transfection blocked ixazomib’s effects. These findings demonstrate that ixazomib regulates mitosis- and apoptosis-related genes by lowering UBE2K expression, which leads to reduce proliferation of myeloma cells. Reference: Biochem Biophys Res Commun. 2021 Apr 16;549:1-7. https://www.sciencedirect.com/science/article/pii/S0006291X21002321?via%3Dihub |
| In vivo activity: | Unlike the KRIB metastatic model, only ixazomib reduced the growth of 143B lung tumors whereas bortezomib was ineffective (Figure 5A). Ixazomib, not bortezomib, also delayed the formation of abdominal metastases (liver and/or kidneys) compared to saline (Figure 5B). Ixazomib-treated mice survived longer and some were asymptomatic at the endpoint of the experiment, whereas most saline- and bortezomib-treated mice required euthanasia due to intolerable tumor-related symptoms (Figure 5C–E). The most striking difference between ixazomib, compared to saline and bortezomib, was the reduced overall tumor burden in the lungs, liver and kidneys ex vivo (Figure 5E). The ex vivo bioluminescence of the lungs in ixazomib-treated mice was at least 100-fold lower than the mice treated with saline or bortezomib, despite being culled up to 21 days later. Reference: Cancers (Basel). 2020 May; 12(5): 1207. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281181/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 100.0 | 193.38 | |
| Ethanol | 100.0 | 193.38 |
The following data is based on the product molecular weight 517.12 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Roeten MSF, van Meerloo J, Kwidama ZJ, Ter Huizen G, Segerink WH, Zweegman S, Kaspers GJL, Jansen G, Cloos J. Pre-Clinical Evaluation of the Proteasome Inhibitor Ixazomib against Bortezomib-Resistant Leukemia Cells and Primary Acute Leukemia Cells. Cells. 2021 Mar 17;10(3):665. doi: 10.3390/cells10030665. PMID: 33802801; PMCID: PMC8002577. 2. Wang Q, Dong Z, Su J, Huang J, Xiao P, Tian L, Chen Y, Ma L, Chen X. Ixazomib inhibits myeloma cell proliferation by targeting UBE2K. Biochem Biophys Res Commun. 2021 Apr 16;549:1-7. doi: 10.1016/j.bbrc.2021.02.048. Epub 2021 Feb 26. PMID: 33647537. 3. Sánchez G, Chalmers S, Ahumada X, Montecinos L, Olmedo I, Eisner V, Riveros A, Kogan MJ, Lavandero S, Pedrozo Z, Donoso P. Inhibition of chymotrypsin-like activity of the proteasome by ixazomib prevents mitochondrial dysfunction during myocardial ischemia. PLoS One. 2020 May 26;15(5):e0233591. doi: 10.1371/journal.pone.0233591. PMID: 32453773; PMCID: PMC7250417. 4. Harris MA, Miles MA, Shekhar TM, Cerra C, Georgy SR, Ryan SD, Cannon CM, Hawkins CJ. The Proteasome Inhibitor Ixazomib Inhibits the Formation and Growth of Pulmonary and Abdominal Osteosarcoma Metastases in Mice. Cancers (Basel). 2020 May 11;12(5):1207. doi: 10.3390/cancers12051207. PMID: 32403415; PMCID: PMC7281181. |
| In vitro protocol: | 1. Roeten MSF, van Meerloo J, Kwidama ZJ, Ter Huizen G, Segerink WH, Zweegman S, Kaspers GJL, Jansen G, Cloos J. Pre-Clinical Evaluation of the Proteasome Inhibitor Ixazomib against Bortezomib-Resistant Leukemia Cells and Primary Acute Leukemia Cells. Cells. 2021 Mar 17;10(3):665. doi: 10.3390/cells10030665. PMID: 33802801; PMCID: PMC8002577. 2. Wang Q, Dong Z, Su J, Huang J, Xiao P, Tian L, Chen Y, Ma L, Chen X. Ixazomib inhibits myeloma cell proliferation by targeting UBE2K. Biochem Biophys Res Commun. 2021 Apr 16;549:1-7. doi: 10.1016/j.bbrc.2021.02.048. Epub 2021 Feb 26. PMID: 33647537. |
| In vivo protocol: | 1. Sánchez G, Chalmers S, Ahumada X, Montecinos L, Olmedo I, Eisner V, Riveros A, Kogan MJ, Lavandero S, Pedrozo Z, Donoso P. Inhibition of chymotrypsin-like activity of the proteasome by ixazomib prevents mitochondrial dysfunction during myocardial ischemia. PLoS One. 2020 May 26;15(5):e0233591. doi: 10.1371/journal.pone.0233591. PMID: 32453773; PMCID: PMC7250417. 2. Harris MA, Miles MA, Shekhar TM, Cerra C, Georgy SR, Ryan SD, Cannon CM, Hawkins CJ. The Proteasome Inhibitor Ixazomib Inhibits the Formation and Growth of Pulmonary and Abdominal Osteosarcoma Metastases in Mice. Cancers (Basel). 2020 May 11;12(5):1207. doi: 10.3390/cancers12051207. PMID: 32403415; PMCID: PMC7281181. |
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