Discovery of K_V 1.3 ion channel inhibitors: Medicinal chemistry approaches and challenges.

"this toxin-like defensin was isolated from the fungus purpureocillium lilacinum and it inhibits k v 1 3 with an ic 50 of 0 2 um 123 figure 5 nmr structures of bmktx 124 (pdb id code: 1bkt) shk 110 (pdb id code: 1roo) osk1 125 (pdb id code: 1sco) hstx1 126 (pdb id code: 1quz) and moka1 104 (pdb id code: 2kir) with labeling of residues thought to be important for binding to kv1 3; design of moka1 by scaffold-/target-biased strategy [color figure can be viewed at wileyonlinelibrary com ] 4 2 many peptides that act on k v 1 3 with excellent potencies have been isolated and described 6 127 a frequently occurring pitfall however is insufficient selectivity for k v 1 3 over other k v channels and especially over k v 1 1 because of its high homology to k v 1 3 (65%-70%) 73 after isolation of an active peptide there are different strategies available to improve the active peptide's selectivity toward the target of interest thereby avoiding potential side effects."

"Jan Tytgat was supported by grants G0E7120N, GOC2319N, and GOA4919N (FWO‐Vlaanderen), and grant CELSA/17/047 (KU Leuven). Steve Peigneur was supported by grant PDM/19/164 (KU Leuven). This project has received funding from the Max‐Planck Society and the European Union through Horizon 2020 Research and Innovation Programme under the Marie Skłodowska‐Curie grant agreement No.: 813834‐PHIONIC‐H2020‐MSCA‐ITN‐2018. Lucija P. Mašič was supported by grants J1‐9192, N1‐0098, P1‐0208 (ARRS; Slovenian Research Agency), and grant CELSA 005‐1/2017 (University of Ljubljana)."