amp 423.

USP7-IN-4(USP7 inhibitor ALM4) is a non-competitive, potent and selective inhibitor of USP7 (ubiquitin-specific protease 7) with an IC50 = 6 nM, up-regulates p53 and p21, down-regulates MDM2, increases the level of ubiquitination of MDM2, and exhibits anti-proliferative activity in a variety of cancer cell lines, with an EC50 = 2.0 nM in RS4;11 (acute lymphoblastic leukemia cell line) .

AMP423 is a naphthyl derivative of 2-cyanoaziridine-1-carboxamide with structural similarity to the pro-oxidant anti-tumor agent imexon. AMP423 was active in SCID mice bearing 8226 S myeloma and SU-DHL-6 B-cell lymphoma tumors, with a median tumor growth delay (T-C) of 21 days (P = 0.0002) and 5 days (P = 0.004), respectively, and a median tumor growth inhibition (T C) of 33.3% (P = 0.03) and 82% (P = 0.01), respectively. In non-tumor-bearing mice, AMP423 was not myelosuppressive.