MLN9708

• CAT Number: M143695
• CAS Number: 1201902-80-8
• Molecular Formula: C20H23BCl2N2O9
• Molecular Weight: 517.119
• Purity: ≥95%
• Synonyms: [(1R)-1-[[2-[(2,5-dichlorobenzoyl)amino]acetyl]amino]-3-methylbutyl]boronic acid
• Target: Proteasome
• Solubility: >20.85mg/mL in DMSO
• Storage: 3 years -20C powder
• IUPAC Name: 4-(carboxymethyl)-2-[(1R)-1-[[2-[(2,5-dichlorobenzoyl)amino]acetyl]amino]-3-methylbutyl]-6-oxo-1,3,2-dioxaborinane-4-carboxylic acid
• InChI: 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
• InChIKey: YTXSYWAKVMZICI-PVCZSOGJSA-N
• 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

MLN9708, also known as ixazomib citrate, 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.

Reference

1:A New Perspective for Osteosarcoma Therapy: Proteasome Inhibition by MLN9708/2238 Successfully Induces Apoptosis and Cell Cycle Arrest and Attenuates the Invasion Ability of Osteosarcoma Cells in Vitro. Liu R, Fu C, Sun J, Wang X, Geng S, Wang X, Zou J, Bi Z, Yang C.Cell Physiol Biochem. 2017;41(2):451-465. doi: 10.1159/000456598. Epub 2017 Jan 27. PMID: 28214890 Free Article2:Next-generation proteasome inhibitor MLN9708 sensitizes breast cancer cells to doxorubicin-induced apoptosis. Wang H, Yu Y, Jiang Z, Cao WM, Wang Z, Dou J, Zhao Y, Cui Y, Zhang H.Sci Rep. 2016 May 24;6:26456. doi: 10.1038/srep26456. PMID: 27217076 Free PMC Article3:Preclinical activity of the oral proteasome inhibitor MLN9708 in Myeloma bone disease. Garcia-Gomez A, Quwaider D, Canavese M, Ocio EM, Tian Z, Blanco JF, Berger AJ, Ortiz-de-Solorzano C, Hernández-Iglesias T, Martens AC, Groen RW, Mateo-Urdiales J, Fraile S, Galarraga M, Chauhan D, San Miguel JF, Raje N, Garayoa M.Clin Cancer Res. 2014 Mar 15;20(6):1542-54. doi: 10.1158/1078-0432.CCR-13-1657. Epub 2014 Jan 31. PMID: 24486586 Free Article4:Ultra high performance liquid chromatography coupled with high resolution quantitation mass spectrometry method development and validation for determining genotoxic 2,5-dichlorobenzoyl chloride in MLN9708 drug substance. Fu M, Lu Q, Hewitt E, Wang J.J Pharm Biomed Anal. 2014 Feb;89:233-9. doi: 10.1016/j.jpba.2013.11.012. Epub 2013 Nov 19. PMID: 24309557 5:Syntheses of C-13 and C-14-labeled versions of the investigational proteasome inhibitor MLN9708. Plesescu M, Elliott EL, Li Y, Prakash SR.J Labelled Comp Radiopharm. 2013 Jul-Aug;56(9-10):464-70. doi: 10.1002/jlcr.3079. Epub 2013 Jul 9. PMID: 24285522 6:Investigational agent MLN9708/2238 targets tumor-suppressor miR33b in MM cells. Tian Z, Zhao JJ, Tai YT, Amin SB, Hu Y, Berger AJ, Richardson P, Chauhan D, Anderson KC.Blood. 2012 Nov 8;120(19):3958-67. doi: 10.1182/blood-2012-01-401794. Epub 2012 Sep 14. PMID: 22983447 Free PMC Article7:Antitumor activity of the investigational proteasome inhibitor MLN9708 in mouse models of B-cell and plasma cell malignancies. Lee EC, Fitzgerald M, Bannerman B, Donelan J, Bano K, Terkelsen J, Bradley DP, Subakan O, Silva MD, Liu R, Pickard M, Li Z, Tayber O, Li P, Hales P, Carsillo M, Neppalli VT, Berger AJ, Kupperman E, Manfredi M, Bolen JB, Van Ness B, Janz S.Clin Cancer Res. 2011 Dec 1;17(23):7313-23. doi: 10.1158/1078-0432.CCR-11-0636. Epub 2011 Sep 8. PMID: 21903769 Free PMC Article8:In vitro and in vivo selective antitumor activity of a novel orally bioavailable proteasome inhibitor MLN9708 against multiple myeloma cells. Chauhan D, Tian Z, Zhou B, Kuhn D, Orlowski R, Raje N, Richardson P, Anderson KC.Clin Cancer Res. 2011 Aug 15;17(16):5311-21. doi: 10.1158/1078-0432.CCR-11-0476. Epub 2011 Jun 30. PMID: 21724551 Free PMC Article9:Evaluation of the proteasome inhibitor MLN9708 in preclinical models of human cancer. Kupperman E, Lee EC, Cao Y, Bannerman B, Fitzgerald M, Berger A, Yu J, Yang Y, Hales P, Bruzzese F, Liu J, Blank J, Garcia K, Tsu C, Dick L, Fleming P, Yu L, Manfredi M, Rolfe M, Bolen J.Cancer Res. 2010 Mar 1;70(5):1970-80. doi: 10.1158/0008-5472.CAN-09-2766. Epub 2010 Feb 16. Erratum in: Cancer Res. 2010 May 1;70(9):3853. Hales, Paul [added]. PMID: 20160034 Free Article