V12

V12 is a novel small molecule p97 inhibitor, belonging to the 5,6,7,8-tetrahydropyridine[2,3-d]pyrimidine derivative series. It was designed and synthesized for the potential treatment of acute myeloid leukemia (AML). V12 inhibits the activity of VCP/p97, an ATPase crucial for endoplasmic reticulum-associated degradation (ERAD), leading to the accumulation of ubiquitylated proteins, activation of the unfolded protein response (UPR), and subsequent apoptosis in cancer cells. Preclinical studies have demonstrated its potent in vitro and in vivo antitumor efficacy against AML, as well as good pharmacokinetic properties and a favorable safety profile in mouse xenograft models. V12 is rapidly metabolized to V13, which also exhibits strong inhibitory activities and good stability.