Discovery of the small molecular inhibitors against TRPV6 as potential anti-cancer agents by structural based virtual screening.

TRPV6 is a member of the transient receptor potential cation channel family with selective permeability to Ca2+. Research indicates that TRPV6 is involved in the promotion of tumor cell proliferation and metastasis in various cancers, rendering it a prospective therapeutic target in cancer treatment. Thus, TRPV6 inhibitors are a very promising avenue for research into novel anti-tumor drugs. Nevertheless, the development of TRPV6 inhibitors remains in the preliminary stage, and the existing TRPV6 inhibitors demonstrate inadequate selectivity and off-target effects. Currently, the development of new drugs is being accelerated greatly by virtual screening technology, as is the reduction of research and development costs. In the present study, a novel TRPV6 inhibitor, designated AZ191, was identified through a structure-based virtual screening process utilizing the MCE and TOPSCIENCE databases. Electrophysiological experiments demonstrated that the compound AZ191 exhibited a high degree of affinity for hTRPV6, with an IC50 of 3.83 ± 0.32 μM. In vitro experiments have demonstrated the efficacy of compound AZ191 in combating tumors by virtue of its inhibitory effect on TRPV6. Notably, our study further demonstrates the good potential of TRPV6 inhibitors as novel anti-cancer drugs and provides a good lead compound for TRPV6 inhibitor research.