MLN2238

MLN2238 is an inhibitor of the beta5 subunit of the 20S proteasome (IC50 = 3.4 nM in a cell-free assay) and an active metabolite of MLN9708 (Cay-18386). It is formed from MLN9708 via hydrolysis in plasma. MLN2238 is selective for the chymotrypsin-like beta5 subunit over the caspase-like beta1 and trypsin-like beta2 subunits (IC50s = 31 and 3,500 nM, respectively). It also binds caseinolytic protease P (Kd = 5,700 nM) and prevents hemolysis of isolated ovine erythrocytes induced by methicillin-resistant S. aureus (MRSA, EC50 = 3,600 nM). MLN2238 inhibits the proliferation of A375 and H460 lung and HCT116 and HT-29 colon cancer cells (IC50s = 20, 58, 19, and 52 nM, respectively) as well as osteoclastogenesis in peripheral blood mononuclear cells (PBMCs) isolated from patients with multiple myeloma (IC50 = 4.8 nM). It reduces tumor growth in a CWR22 prostate cancer mouse xenograft model when administered at a dose of 14 mg/kg. Formulations containing MLN2238 have been used in the treatment of multiple myeloma.Formal Name: B-[(1R)-1-[[2-[(2,5-dichlorobenzoyl)amino]acetyl]amino]-3-methylbutyl]-boronic acid. CAS Number: 1072833-77-2. Molecular Formula: C14H19BCl2N2O4. Formula Weight: 361.0. Purity: >95%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 30 mg/ml, DMF:PBS(pH 7.2)(1:1): 0.5 mg/ml, DMSO: 20 mg/ml, Ethanol: 25 mg/ml. SMILES: ClC1=C(C(NCC(N[C@H](B(O)O)CC(C)C)=O)=O)C=C(Cl)C=C1. InChi Code: InChI=1S/C14H19BCl2N2O4/c1-8(2)5-12(15(22)23)19-13(20)7-18-14(21)10-6-9(16)3-4-11(10)17/h3-4,6,8,12,22-23H,5,7H2,1-2H3,(H,18,21)(H,19,20)/t12-/m0/s1. InChi Key: MXAYKZJJDUDWDS-LBPRGKRZSA-N.