Therapeutics: Pim-1 (PIM1); Pim-2 (PIM2)

In vitro and mouse studies identified a quinazolinone-based inhibitor of PIM1 and PIM2 that could help treat MM. Chemical synthesis and in vitro testing of quinazolinone-pyrrolopyrrolone analogs yielded one compound that inhibited PIM1 and PIM2 with IC50 values of 0.2 and 0.3 nM, respectively. In a xenograft mouse model of MM, the compound decreased tumor growth compared with vehicle. Next steps could include testing the compound in additional animal models of MM.

Novartis AG has PIM447, an oral pan-PIM kinase inhibitor, in Phase I/II testing to treat MM and Phase I testing to treat acute myelogenous leukemia (AML) and myeloproliferative disorder...