Structural highlights
Function
[KAX54_HOTTA] Blocks small conductance calcium-activated potassium channels (PubMed:12239213). Shows activity on KCa2.2/KCNN2 (IC(50)=0.0243 nM), KCa2.3/KCNN3 (IC(50)=1.7 nM), and KCa2.1/KCNN1 (IC(50)=42 nM) (PubMed:12239213). Induces cell death when tested on Jurkat E6-1 and human mammary breast cancer MDA-MB-231 which constituvely express KCa2.2/KCNN2, but not on human peripheral blood lymphocytes (which do not express KCa2.2/KCNN2) (PubMed:24821061).[1]
Publication Abstract from PubMed
Peptide-based therapy against cancer is a field of great interest for biomedical developments. Since it was shown that SK3 channels promote cancer cell migration and metastatic development, we started using these channels as targets for the development of antimetastatic drugs. Particularly, tamapin (a peptide found in the venom of the scorpion Mesobuthus tamulus) is the most specific toxin against the SK2 channel currently known. Considering this fact, we designed diverse tamapin mutants based on three different hypotheses to discover a new potent molecule to block SK3 channels. We performed in vitro studies to evaluate this new toxin derivative inhibitor of cancer cell migration. Our results can be used to generate a new tamapin-based therapy against cancer cells that express SK3 channels.
Novel Blocker of Onco SK3 Channels Derived from Scorpion Toxin Tamapin and Active against Migration of Cancer Cells.,Mayorga-Flores M, Chantome A, Melchor-Meneses CM, Domingo I, Titaux-Delgado GA, Galindo-Murillo R, Vandier C, Del Rio-Portilla F ACS Med Chem Lett. 2020 Jul 10;11(8):1627-1633. doi:, 10.1021/acsmedchemlett.0c00300. eCollection 2020 Aug 13. PMID:32832033[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Pedarzani P, D'hoedt D, Doorty KB, Wadsworth JD, Joseph JS, Jeyaseelan K, Kini RM, Gadre SV, Sapatnekar SM, Stocker M, Strong PN. Tamapin, a venom peptide from the Indian red scorpion (Mesobuthus tamulus) that targets small conductance Ca2+-activated K+ channels and afterhyperpolarization currents in central neurons. J Biol Chem. 2002 Nov 29;277(48):46101-9. Epub 2002 Sep 17. PMID:12239213 doi:http://dx.doi.org/10.1074/jbc.M206465200
- ↑ Mayorga-Flores M, Chantome A, Melchor-Meneses CM, Domingo I, Titaux-Delgado GA, Galindo-Murillo R, Vandier C, Del Rio-Portilla F. Novel Blocker of Onco SK3 Channels Derived from Scorpion Toxin Tamapin and Active against Migration of Cancer Cells. ACS Med Chem Lett. 2020 Jul 10;11(8):1627-1633. doi:, 10.1021/acsmedchemlett.0c00300. eCollection 2020 Aug 13. PMID:32832033 doi:http://dx.doi.org/10.1021/acsmedchemlett.0c00300
