MLN2238

• CAT Number: I000335
• CAS Number: 1072833-77-2
• Molecular Formula: C14H19BCl2N2O4
• Molecular Weight: 361
• Purity: ≥95%
• Target: Proteasome
• Solubility: DMSO 72 mg/mL; Water <1 mg/mL; Ethanol 9 mg/mL
• Storage: 3 years -20C powder
• IC50: 3.4 nM (20S proteasome ) [1]
• InChIKey: MXAYKZJJDUDWDS-LBPRGKRZSA-N

MLN2238(CAT: I000335), also known as ixazomib, is an orally bioavailable proteasome inhibitor that is used to treat multiple myeloma. It selectively inhibits the beta-5 subunit of the 20S proteasome, which is responsible for the degradation of intracellular proteins, leading to an accumulation of misfolded or damaged proteins and eventually inducing apoptosis of cancer cells. It is the first oral proteasome inhibitor to be approved by the US Food and Drug Administration for the treatment of multiple myeloma in combination with lenalidomide and dexamethasone.

Reference

1:The combination of MLN2238 (ixazomib) with interferon-alpha results in enhanced cell death in melanoma. Suarez-Kelly LP, Kemper GM, Duggan MC, Stiff A, Noel TC, Markowitz J, Luedke EA, Yildiz VO, Yu L, Jaime-Ramirez AC, Karpa V, Zhang X, Carson WE 3rd.Oncotarget. 2016 Dec 6;7(49):81172-81186. doi: 10.18632/oncotarget.12791. PMID: 27783987 Free PMC Article2:Comparison of antiproliferative and apoptotic effects of a novel proteasome inhibitor MLN2238 with bortezomib on K562 chronic myeloid leukemia cells. Engür S, Dikmen M, Öztürk Y.Immunopharmacol Immunotoxicol. 2016;38(2):87-97. doi: 10.3109/08923973.2015.1122616. Epub 2015 Dec 15. PMID: 26667773 3:MLN2238 synergizes BH3 mimetic ABT-263 in castration-resistant prostate cancer cells by induction of NOXA. Wei X, Zhou P, Lin X, Lin Y, Wu S, Diao P, Xie H, Xie K, Tang P.Tumour Biol. 2014 Oct;35(10):10213-21. doi: 10.1007/s13277-014-2333-y. Epub 2014 Jul 17. PMID: 25027405 4:The investigational agent MLN2238 induces apoptosis and is cytotoxic to CLL cells in vitro, as a single agent and in combination with other drugs. Paulus A, Masood A, Miller KC, Khan AN, Akhtar D, Advani P, Foran J, Rivera C, Roy V, Colon-Otero G, Chitta K, Chanan-Khan A.Br J Haematol. 2014 Apr;165(1):78-88. doi: 10.1111/bjh.12731. Epub 2014 Jan 27. PMID: 24467634 5:MLN2238, a proteasome inhibitor, induces caspase-dependent cell death, cell cycle arrest, and potentiates the cytotoxic activity of chemotherapy agents in rituximab-chemotherapy-sensitive or rituximab-chemotherapy-resistant B-cell lymphoma preclinical models. Gu JJ, Hernandez-Ilizaliturri FJ, Mavis C, Czuczman NM, Deeb G, Gibbs J, Skitzki JJ, Patil R, Czuczman MS.Anticancer Drugs. 2013 Nov;24(10):1030-8. doi: 10.1097/CAD.0000000000000008. PMID: 23995855