MLN2238

MLN2238 is an inhibitor of the β5 subunit of the 20S proteasome (IC₅₀ = 3.4 nM in a cell-free assay) and an active metabolite of MLN9708 (Item No. 18386).^1,2 It is formed from MLN9708 via hydrolysis in plasma.¹ MLN2238 is selective for the chymotrypsin-like β5 subunit over the caspase-like β1 and trypsin-like β2 subunits (IC₅₀s = 31 and 3,500 nM, respectively). It also binds caseinolytic protease P (K_d = 5,700 nM) and prevents hemolysis of isolated ovine erythrocytes induced by methicillin-resistant S. aureus (MRSA; EC₅₀ = 3,600 nM).³ 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).^1,2 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.

WARNING This product is not for human or veterinary use.

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

2. Garcia-Gomez, A., Quwaider, D., Canavese, M., et al. Preclinical activity of the oral proteasome inhibitor MLN9708 in Myeloma bone disease. Clin. Cancer Res. 20(6), 1542-1554 (2014).

3. Ju, Y., He, L., Zhou, Y., et al. Discovery of novel peptidomimetic boronate ClpP inhibitors with noncanonical enzyme mechanism as potent virulence blockers in vitro and in vivo. J. Med. Chem. 63(6), 3104-3119 (2020).