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A potent blocker of Neuronal TTX-Sensitive Voltage-Gated Na+ Channel that preferentially inhibits neuronal voltage-gated sodium channel subtype hNav1.7 (SCN9A) (IC50 = 26 nM), rNav1.2 (SCN2A) (IC50 = 150 nM), and rNav1.3 (SCN3A) (IC50 = 338 nM), compared with muscle subtypes rNav1.4 (SCN4A) and hNav1.5 (SCN5A) (IC50 > 10 µM). Huwentoxin IV inhibits the activation of sodium channels by trapping the voltage sensor of domain II of the site 4 in the inward, closed configuration.
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M.F/Formula | C174H278N52O51S6 |
M.W/Mr. | 4106.79 |
Sequence | ECLEIFKACNPSNDQCCKSSKLVCSRKTRWCKYQI(Disulfide bridge: Cys2 and Cys17,Cys9 and Cys24,Cys16 and Cys31) |
Labeling Target | TTX-sensitive Na+ channels |
Appearance | White lyophilised solid |
Purity | >99% |
Activity | Blocker |
Long-term Storage Conditions | Soluble in water |
InChI | InChI=1S/C174H278N52O51S6/c1-13-87(9)135(138(185)243)223-149(254)106(51-54-128(182)234)201-152(257)110(68-92-45-47-94(232)48-46-92)206-144(249)100(39-22-27-59-177)198-162(267)122-80-280-282-82-124-167(272)220-123-81-281-279-79-121(217-140(245)96(180)49-55-131(237)238)164(269)205-108(65-84(3)4)151(256)202-107(52-56-132(239)240)150(255)224-136(88(10)14-2)170(275)210-111(67-91-33-16-15-17-34-91)153(258)195-98(37-20-25-57-175)141(246)193-89(11)139(244)216-120(165(270)211-115(71-130(184)236)172(277)226-64-32-44-126(226)168(273)215-119(77-230)160(265)208-113(70-129(183)235)155(260)209-114(72-133(241)242)156(261)200-105(147(252)218-124)50-53-127(181)233)78-278-283-83-125(221-169(274)134(86(7)8)222-157(262)109(66-85(5)6)204-143(248)99(38-21-26-58-176)196-158(263)116(74-227)213-161(266)118(76-229)212-146(251)101(199-163(123)268)40-23-28-60-178)166(271)214-117(75-228)159(264)197-103(42-30-62-190-173(186)187)142(247)194-102(41-24-29-61-179)148(253)225-137(90(12)231)171(276)203-104(43-31-63-191-174(188)189)145(250)207-112(154(259)219-122)69-93-73-192-97-36-19-18-35-95(93)97/h15-19,33-36,45-48,73,84-90,96,98-126,134-137,192,227-232H,13-14,20-32,37-44,49-72,74-83,175-180H2,1-12H3,(H2,181,233)(H2,182,234)(H2,183,235)(H2,184,236)(H2,185,243)(H,193,246)(H,194,247)(H,195,258)(H,196,263)(H,197,264)(H,198,267)(H,199,268)(H,200,261)(H,201,257)(H,202,256)(H,203,276)(H,204,248)(H,205,269)(H,206,249)(H,207,250)(H,208,265)(H,209,260)(H,210,275)(H,211,270)(H,212,251)(H,213,266)(H,214,271)(H,215,273)(H,216,244)(H,217,245)(H,218,252)(H,219,259)(H,220,272)(H,221,274)(H,222,262)(H,223,254)(H,224,255)(H,225,253)(H,237,238)(H,239,240)(H,241,242)(H4,186,187,190)(H4,188,189,191) |
InChI Key | MJMLBAPXMAOKDU-UHFFFAOYSA-N |
References | Huwentoxin-IV (HWTX-IV), similarly to JZTX-34, inhibited neuronal TTX-sensitive voltage-gated sodium channels with an IC50 value of 30 nM in adult rat dorsal root ganglion neurons (DRG neurons), but have no significant effect on TTX-resistant voltage-gated sodium channels. Recently studies demonstrated that ProTx-II and HWTX-IV binding determinants on domain-II may overlap, with domain II playing a much more crucial role for HWTX-IV. The date also proved that the inhibition of sodium currents could be reversible by strong depolarization due to the dissociation of HWTX-IV. Native Pyroglutamation of Huwentoxin-IV: A Post-Translational Modification that Increases the Trapping Ability to the Sodium Channel |
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