ONX 0912

ONX 0912 is an orally bioavailable proteasome inhibitor.¹ It potently targets the chymotrypsin-like activity of the 20S proteasome subunits β5 and LMP7 (IC₅₀s = 36 and 82 nM, respectively).¹ ONX 0912 inhibits the growth of multiple myeloma cells at nanomolar concentrations while not decreasing the viability of normal peripheral blood mononuclear cells at 1 µM.² It blocks the growth of xenografted human multiple myeloma cells in mice when given orally.² ONX 0912 has potential applications in certain types of cancer as well as other diseases that require proteasome activity.^3,4,5,6

WARNING This product is not for human or veterinary use.

1. Zhou, H.J., Aujay, M.A., Bennett, M.K., et al. Design and synthesis of an orally bioavailable and selective peptide epoxyketone proteasome inhibitor (PR-047). J. Med. Chem. 52(9), 3028-3038 (2009).

2. Chauhan, D., Singh, A.V., Aujay, M., et al. A novel orally active proteasome inhibitor ONX 0912 triggers in vitro and in vivo cytotoxicity in multiple myeloma. Blood 116(23), 4906-4915 (2010).

3. Mato, A.R., Feldman, T., and Goy, A. Proteasome inhibition and combination therapy for non-Hodgkin’s lymphoma: From bench to bedside. Oncologist 17(5), 694-707 (2012).

4. Niewerth, D., Franke, N.E., Jansen, G., et al. Higher ratio immune versus constitutive proteasome level as novel indicator of sensitivity of pediatric acute leukemia cells to proteasome inhibitors. Haematologica 98(12), 1896-1904 (2013).

5. Gupta, S., Wang, L., Anderl, J., et al. Correction of cystathionine β-synthase deficiency in mice by treatment with proteasome inhibitors. Hum. Mutat. 34(8), 1085-1093 (2013).

6. Dou, Q.P., and Zonder, J.A. Overview of proteasome inhibitor-based anti-cancer therapies: Perspective on bortezomib and second generation proteasome inhibitors versus future generation inhibitors of ubiquitin-proteasome system. Curr. Cancer Drug Targets 14(6), 517-536 (2014).