| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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Purity: ≥98%
MLN9708 (also known as ixazomib citrate; MLN-9708; trade name Ninlaro), the citrate salt of Ixazomib (MMLN2238; MMLN-2238), is a prodrug of Ixazomib (MMLN-2238) which is an orally bioavailable and 2nd generation proteasome inhibitor (PI) with potential antineoplastic activity. The boron-containing compound ixazomib citrate needs to be hydrolyzed to yield the pharmacologically active compound MLN2238 (ixazomib). Preclinical studies have shown that MLN9708 has better antitumor activity, pharmacokinetics, and pharmacodynamics than bortezomib. In cell-free assays, MLN2238 inhibits the chymotrypsin-like proteolytic (β5) site of the 20S proteasome with an IC50/Ki of 3.4 nM/0.93 nM; it has little activity against β2 and is less potent against β1. Excellent antitumor activity is demonstrated by MLN9708 in hematologic preclinical xenograft models as well as solid tumor models.
| Targets |
20S proteasome (Ki = 0.93 nM); 20S proteasome (IC50 = 3.4 nM)
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| ln Vitro |
MLN9708 is a selective, orally bioavailable, second-generation proteasome inhibitor. We believe that MLN9708's improved tissue distribution is largely due to its shorter proteasome dissociation half-life, as well as its improved pharmacokinetics, pharmacodynamics, and antitumor activity when compared to bortezomib. In addition to having a larger blood volume distribution at steady state than bortezomib, MLN9708 also exhibits greater pharmacodynamic effects in tissues when compared to markers of the unfolded protein response and 20S proteasome inhibition. A second-generation small-molecule proteasome inhibitor called MLN9708 is being developed to treat a variety of cancers in humans. When exposed to plasma or aqueous solutions, MLN9708 hydrolyzes quickly to produce MLN2238, which is biologically active. The biologically active form of MLN9708 is MLN2238.
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| ln Vivo |
MLN9708 exhibits better antitumor activity when given via various dosage routes and regimens in both solid tumor and hematologic preclinical xenograft models. Preclinical pharmacology studies conducted recently have demonstrated that MLN9708 exhibits better pharmacokinetics, pharmacodynamics, and antitumor activity in xenograft models compared to bortezomib, along with a shorter proteasome dissociation half-life. With a variety of tumor xenografts, MLN9708 has demonstrated antitumor efficacy.
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| Enzyme Assay |
Before the experiment begins, Calu-6 cells are plated in a 384-well plate at a density of 1 × 104 cells per well, in medium supplemented with 10% fetal bovine serum and 1% penicillin/streptomycin. By employing the Proteasome-Glo assay reagents in accordance with the manufacturer's instructions and monitoring the hydrolysis of the chymotrypsin-like substrate Suc-LLVY-aminoluciferin in the presence of luciferase, proteasome activity is measured. With a LEADseeker device, luminosity is measured.
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| Cell Assay |
Before the experiment begins, Calu-6 cells are plated in a 384-well plate at a density of 1 × 104 cells per well, in medium supplemented with 10% FBS and 1% penicillin/streptomycin. The IC50 values are obtained by treating cells for one hour at 37 °C with different concentrations of MLN2238 or boratezomib in DMSO (0.5% final, v/v). For reversibility tests, cells are exposed to either MLN2238 or 1 μM Bortezomib for thirty minutes at 37 °C. After that, the cells are three times washed in medium to get rid of the MLN2238 or Bortezomib. The medium is removed and fresh medium is added after the cells are incubated for an additional 4 hours at 37 °C.
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| Animal Protocol |
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| References |
| Molecular Formula |
C20H23BCL2N2O9
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| Molecular Weight |
517.12
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| Exact Mass |
516.09
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| Elemental Analysis |
C, 46.45; H, 4.48; B, 2.09; Cl, 13.71; N, 5.42; O, 27.85
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| CAS # |
1201902-80-8
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| Related CAS # |
1239908-20-3 (citrate); 2026591-78-4 (i-PrOH); 1072833-77-2 (free); 1201902-80-8 2026591-78-4 (EtOH)
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| Appearance |
White to off-white solid powder
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| SMILES |
B1(OC(=O)CC(O1)(CC(=O)O)C(=O)O)[C@H](CC(C)C)NC(=O)CNC(=O)C2=C(C=CC(=C2)Cl)Cl
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| InChi Key |
YTXSYWAKVMZICI-PVCZSOGJSA-N
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| InChi Code |
InChI=1S/C20H23BCl2N2O9/c1-10(2)5-14(21-33-17(29)8-20(34-21,19(31)32)7-16(27)28)25-15(26)9-24-18(30)12-6-11(22)3-4-13(12)23/h3-4,6,10,14H,5,7-9H2,1-2H3,(H,24,30)(H,25,26)(H,27,28)(H,31,32)/t14-,20?/m0/s1
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| Chemical Name |
4-(carboxymethyl)-2-[(1R)-1-[[2-[(2,5-dichlorobenzoyl)amino]acetyl]amino]-3-methylbutyl]-6-oxo-1,3,2-dioxaborinane-4-carboxylic acid
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| Synonyms |
Ninlaro; MLN9708; MLN 9708; MLN-9708; MMLN-2238-prodrug; MMLN 2238-prodrug; Ixazomib-prodrug; MMLN2238-prodrug; ixazomib citrate
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
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| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02924272 | Active Recruiting |
Drug: Ixazomib | Lymphoma Amyloidosis |
Takeda | December 16, 2016 | Phase 2 |
| NCT04028115 | Active Recruiting |
Drug: Ixazomib | Multiple Myeloma | Thomas Lund | October 24, 2019 | Phase 2 |
| NCT04837131 | Recruiting | Drug: Ixazomib | Scleroderma Systemic Sclerosis |
W. Leroy Griffing | April 28, 2021 | Phase 2 |
| NCT02632396 | Active Recruiting |
Drug: Ixazomib Biological: Rituximab |
Mantle Cell Lymphoma | Emory University | March 1, 2016 | Phase 1 Phase 2 |
| NCT03618537 | Recruiting | Drug: Ixazomib Drug: Dexamethasone |
AL Amyloidosis | Memorial Sloan Kettering Cancer Center |
August 2, 2018 | Phase 2 |
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