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Adhesion regulating molecule 1 (ADRM1; RPN13)

In vitro and mouse studies suggest inhibiting the RPN13 proteasomal component could help treat cancer. In vitro, a bis-benzylidine piperidone bound to the pleckstrin-like receptor for ubiquitin domain of RPN13. In cancer cell lines, the compound induced accumulation of polyubiquitinated proteins and apoptosis at a rate similar to or faster than Velcade bortezomib. In mouse models of multiple myeloma, ovarian cancer and human papilloma virus-related cancer, the compound inhibited tumor growth. Next steps include optimizing the drug-like properties and oral availability of the compound.
Takeda Pharmaceutical Co. Ltd. markets Velcade to treat multiple myeloma (MM) and mantle cell lymphoma (MCL; see Putting a lid on cancer cell proteasomes, page 7).

SciBX 7(2); doi:10.1038/scibx.2014.48
Published online Jan. 16, 2014

Patent application filed; available for licensing

Anchoori, R.K. et al. Cancer Cell; published online Dec. 9, 2013;
Contact: Richard B.S. Roden, The Johns Hopkins University, Baltimore, Md.