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- W4313236941 abstract "The voltage-gated sodium NaV1.7 channel plays a key role as a mediator of action potential propagation in C-fiber nociceptors and is an established molecular target for pain therapy. ProTx-II is a potent and moderately selective peptide toxin from tarantula venom that inhibits human NaV1.7 activation. Here we used available structural and experimental data to guide Rosetta design of potent and selective ProTx-II-based peptide inhibitors of human NaV1.7 channels. Functional testing of designed peptides using electrophysiology identified the PTx2-3127 and PTx2-3258 peptides with IC50s of 7 nM and 4 nM for hNaV1.7 and more than 1000-fold selectivity over human NaV1.1, NaV1.3, NaV1.4, NaV1.5, NaV1.8, and NaV1.9 channels. PTx2-3127 inhibits NaV1.7 currents in mouse and human sensory neurons and shows efficacy in rat models of chronic and thermal pain when administered intrathecally. Rationally designed peptide inhibitors of human NaV1.7 channels have transformative potential to define a new class of biologics to treat pain." @default.
- W4313236941 created "2023-01-06" @default.
- W4313236941 creator A5000615664 @default.
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- W4313236941 creator A5079484361 @default.
- W4313236941 creator A5087293334 @default.
- W4313236941 creator A5001999478 @default.
- W4313236941 date "2022-12-28" @default.
- W4313236941 modified "2023-10-16" @default.
- W4313236941 title "Computational design of peptides to target NaV1.7 channel with high potency and selectivity for the treatment of pain" @default.
- W4313236941 cites W1481443370 @default.
- W4313236941 cites W1500868300 @default.
- W4313236941 cites W1535530651 @default.
- W4313236941 cites W1560013893 @default.
- W4313236941 cites W1574909190 @default.
- W4313236941 cites W163561699 @default.
- W4313236941 cites W1900662348 @default.
- W4313236941 cites W1969644422 @default.
- W4313236941 cites W1972399880 @default.
- W4313236941 cites W1993584057 @default.
- W4313236941 cites W2012943391 @default.
- W4313236941 cites W2017561737 @default.
- W4313236941 cites W2018459912 @default.
- W4313236941 cites W2018764168 @default.
- W4313236941 cites W2021520922 @default.
- W4313236941 cites W2025185593 @default.
- W4313236941 cites W2026551512 @default.
- W4313236941 cites W2031350286 @default.
- W4313236941 cites W2037355835 @default.
- W4313236941 cites W2039787163 @default.
- W4313236941 cites W2043379591 @default.
- W4313236941 cites W2046392857 @default.
- W4313236941 cites W2047648703 @default.
- W4313236941 cites W2050725524 @default.
- W4313236941 cites W2075715972 @default.
- W4313236941 cites W2081261059 @default.
- W4313236941 cites W2082801748 @default.
- W4313236941 cites W2083509273 @default.
- W4313236941 cites W2086690624 @default.
- W4313236941 cites W2098007639 @default.
- W4313236941 cites W2100936946 @default.
- W4313236941 cites W2101745948 @default.
- W4313236941 cites W2104415321 @default.
- W4313236941 cites W2106140689 @default.
- W4313236941 cites W2108114952 @default.
- W4313236941 cites W2108438677 @default.
- W4313236941 cites W2108916282 @default.
- W4313236941 cites W2109154308 @default.
- W4313236941 cites W2121044649 @default.
- W4313236941 cites W2122467599 @default.
- W4313236941 cites W2127494940 @default.
- W4313236941 cites W2130496291 @default.
- W4313236941 cites W2132856129 @default.
- W4313236941 cites W2136814558 @default.
- W4313236941 cites W2138809708 @default.
- W4313236941 cites W2138839177 @default.
- W4313236941 cites W2139759734 @default.
- W4313236941 cites W2142484144 @default.
- W4313236941 cites W2142796780 @default.
- W4313236941 cites W2143457814 @default.
- W4313236941 cites W2147466595 @default.
- W4313236941 cites W2156848191 @default.
- W4313236941 cites W2158602841 @default.
- W4313236941 cites W2159332152 @default.
- W4313236941 cites W2159470318 @default.
- W4313236941 cites W2162638563 @default.
- W4313236941 cites W2171785121 @default.
- W4313236941 cites W2197214562 @default.
- W4313236941 cites W2283252828 @default.
- W4313236941 cites W2315562298 @default.
- W4313236941 cites W2322319898 @default.
- W4313236941 cites W2487638977 @default.
- W4313236941 cites W2560346424 @default.
- W4313236941 cites W2562806882 @default.
- W4313236941 cites W2586208579 @default.
- W4313236941 cites W2587120326 @default.
- W4313236941 cites W2601843523 @default.
- W4313236941 cites W2606254225 @default.
- W4313236941 cites W2609743128 @default.
- W4313236941 cites W2741464172 @default.
- W4313236941 cites W2779347386 @default.
- W4313236941 cites W2791129791 @default.
- W4313236941 cites W2797740590 @default.
- W4313236941 cites W2801611152 @default.
- W4313236941 cites W2896902447 @default.
- W4313236941 cites W2897315545 @default.
- W4313236941 cites W2909407702 @default.
- W4313236941 cites W2911906719 @default.