Selective TRPV2 Antagonists Derived from the Natural Product Piperlongumine Inhibit Cancer Cell Migration and Metastasis - PubMed
3 hours ago
- #TRPV2 antagonists
- #cancer metastasis
- #drug selectivity
- TRPV2 is a poorly studied ion channel with implications in cancer metastasis, pain, and inflammation, but existing modulators lack selectivity.
- A series of derivatives were developed from the natural product piperlongumine (PL) to create selective TRPV2 antagonists, such as HKC54, which shows high potency (IC50 = 0.4 μM) and selectivity over related channels TRPV1 and TRPA1.
- Through assays and molecular studies, the derivatives engage TRPV2 directly with a binding mode similar to PL, and chemoproteomic analysis indicated minimal off-target effects for the noncovalent derivative HKC22.
- These PL-derived compounds effectively inhibit cancer cell migration in vitro and reduce metastasis in vivo, highlighting their potential as therapeutic agents against cancer.