Huwentoxin IV

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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CAT#	R0984
CAS	526224-73-7
Background	Huwentoxin-IV (HWTX-IV), a tetrodotoxin-sensitive (TTX-s) sodium channel antagonist, is found in the venom of the Chinese spider Ornithoctonus huwena. A naturally modified HWTX-IV (mHWTX-IV), having a molecular mass 18 Da lower than HWTX-IV, has also been isolated from the venom of the same spider. By a combination of enzymatic fragmentation and MS/MS de novo sequencing, mHWTX-IV has been shown to have the same amino acid sequence as that of HWTX-IV, except that the N-terminal glutamic acid replaced by pyroglutamic acid. >> Read More
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

CAT#	Product Name	M.W	Molecular Formula	Inquiry
R0846	cGMP Dependent Kinase Inhibitor Peptide	943.12	C38H74N18O10	Inquiry
R0847	Bax inhibitor peptide, negative control	600.82	C28H52N6O6S	Inquiry
R0852	RAGE antagonist peptide	1272.56	C57H101N13O17S	Inquiry
R0855	G-Protein antagonist peptide	1093.27	C57H64N12O9S	Inquiry
R0856	Compstatin control peptide	1488.67	C66H101N23O17	Inquiry

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Storage	-20°C
Solubility	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