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MLN9708Proteasome inhibitor

MLN9708

Catalog No. A4007
Size Price Stock Qty
Evaluation Sample $28.00 In stock
5mg $90.00 In stock
10mg $150.00 In stock
50mg $450.00 In stock
100mg $640.00 In stock

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Sample solution is provided at 25 µL, 10mM.

Quality Control

Quality Control & MSDS

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Chemical structure

MLN9708

Related Biological Data

MLN9708

Related Biological Data

MLN9708

Protocol

Cell experiment: [1]

Cell lines

MM.1S (Dexamethasone sensitive) cells

Preparation method

The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.

Reacting condition

100 nM, 3 hours for CT-L proteasome inhibition 100 nm, 3 hours for C-L proteasome inhibition 10 μM, 3 hours for T-L proteasome inhibition

Applications

MLN9708 significantly inhibited CT-L proteasome activity with an IC50 at 5 nM. Higher concentrations of MLN9708 showed inhibitory activity against C-L and T-L proteasome activities.

Animal experiment:

Animal models

Female CB17-SCID mice bearing WSU-DLCL2 xenografts

Dosage form

Intravenous injection, 14 mg/kg, twice weekly or subcutaneous injection, 4 mg/kg, once daily

Application

Both intermittent and continuous MLN2238 dosing regimens showed strong antitumor activity (T/C = 0.44 and 0.29 for 14 mg/kg i.v. and 4 mg/kg s.c., respectively) and generated a greater apoptotic response in tumor tissue asmeasured by levels of cleaved caspase-3.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1] Chauhan D, Tian Z, Zhou B, et al. In vitro and in vivo selective antitumor activity of a novel orally bioavailable proteasome inhibitor MLN9708 against multiple myeloma cells. Clinical Cancer Research, 2011, 17(16): 5311-5321.

[2] Kupperman E, Lee E C, Cao Y, et al. Evaluation of the proteasome inhibitor MLN9708 in preclinical models of human cancer. Cancer research, 2010, 70(5): 1970-1980.

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Chemical Properties

Cas No. 1201902-80-8 SDF Download SDF
Synonyms MLN-9708, MLN 9708
Chemical Name [(1R)-1-[[2-[(2,5-dichlorobenzoyl)amino]acetyl]amino]-3-methylbutyl]boronic acid
Canonical SMILES B1(OC(=O)CC(O1)(CC(=O)O)C(=O)O)C(CC(C)C)NC(=O)CNC(=O)C2=C(C=CC(=C2)Cl)Cl
Formula C20H23BCl2N2O9 M.Wt 517.1
Solubility Soluble in DMSO > 10 mM Storage Store at -20°C
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
Shipping Condition Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request

Research Update

1. Syntheses of C-13 and C-14-labeled versions of the investigational proteasome inhibitor MLN9708. J Labelled Comp Radiopharm. 2013 Jul-Aug;56(9-10):464-70. doi: 10.1002/jlcr.3079. Epub 2013 Jul 9.
Abstract
Radiolabeled MLN9708, a proteasome inhibitor with antitumor activity, were synthesized and evaluated for its stability.
2. Antitumor activity of the investigational proteasome inhibitor MLN9708 in mouse models of B-cell and plasma cell malignancies. Clin Cancer Res. 2011 Dec 1;17(23):7313-23. doi: 10.1158/1078-0432.CCR-11-0636. Epub 2011 Sep 8.
Abstract
MLN9708 is a proteasome inhibitor with improved pharmacokinetics, pharmacodynamics and antitumor activity in comparison to bortezomib.
3. Investigational agent MLN9708/2238 targets tumor-suppressor miR33b in MM cells. Blood. 2012 Nov 8;120(19):3958-67. doi: 10.1182/blood-2012-01-401794. Epub 2012 Sep 14.
Abstract
MLN2238, a proteasome inhibitor, induced the expression of miR33b predominantly through transcriptional regulation and negatively regulated oncogene PIM-1 blocking wild-type PIM-1 in MM cells.
4. Preclinical Activity of the Oral Proteasome Inhibitor MLN9708 in Myeloma Bone Disease. Clin Cancer Res. 2014 Feb 27. [Epub ahead of print]
Abstract
MLN2238, an active form of MLN9708, inhibited in vitro osteoclastogenesis and osteoclast resorption and promoted in vitro osteoblastogensis and osteoblast activity at clinically achievable concentrations. Compared to bortezomib, oral administration of MLN2238 exhibited equivalent tumor burden controlling efficacy with a marked benefit in associated bone disease.

Background

MLN9708, also known as ixazomib, is a second-generation small-molecule proteasome inhibitor. It is a citrate ester that immediately hydrolyzes to its biologically active form MLN2238 upon exposure to aqueous solutions or plasma. MLN9708 was selected from a large pool of boron-containing proteasome inhibitors based on a physicochemical profile that was distinct from bortezomib. MLN9708 has a shorter 20S proteasome dissociation half-life than bortezomib, which is demonstrated to play an important role in its improved tissue distribution.

Reference

Erik Kupperman, Edmund C. Lee, Yueying Cao, Bret Bannerman, Michael Fitzgerald, Allison Berger, Jie Yu, Yu Yang, Paul Hales, Frank Bruzzese, Jane Liu, Jonathan Blank, Khristofer Garcia, Christopher Tsu, Larry Dick, Paul Fleming, Li Yu, Mark Manfredi, Mark Rolfe, and Joe Bolen. Evaluation of the Proteasome Inhibitor MLN9708 in Preclinical Models of Human Cancer. Cancer Res March 1, 2010 70; 1970.

Edmund C. Lee, Michael Fitzgerald, Bret Bannerman, Jill Donelan, Kristen Bano, Jennifer Terkelsen, Daniel P. Bradley, Ozlem Subakan, Matthew D. Silva, Ray Liu, Michael Pickard, Zhi Li, Olga Tayber, Ping Li, Paul Hales, Mary Carsillo, Vishala T. Neppalli, Allison J. Berger, Erik Kupperman, Mark Manfredi, Joseph B. Bolen, Brian Van Ness, Siegfried Janz. Antitumor Activity of the Investigational Proteasome Inhibitor MLN9708 in Mouse Models of B-cell and Plasma Cell Malignancies. Clin Cancer Res December 1, 2011 17; 7313.