ProTx-I 

ProTx-I is a toxin derived from Thrixopelma pruriens and a peptide inhibitor targeting TTX-resistant sodium channels. ProTx-I interacts with voltage sensors of multiple domains such as NaV1.7, reduces neuronal excitability through allosteric modulation of channel gating and alteration of voltage dependence. The IC₅₀ values of ProTx-I against human NaV1.7, NaV1.2, NaV1.6, and NaV1.5 are 95 nM, 104 nM, 21 nM, and 358 nM, respectively; ProTx-I also potently inhibits Ba²⁺ currents of hCav3.1, while its inhibitory potency against hCav3.2 is approximately 160-fold lower. ProTx-I is applicable to the research of chronic pain^[1][2][3].

ProTx-I (0.01-10 μM; ~7-30 min) potently inhibits Ba²⁺ currents through hCav3.1-expressing Xenopus laevis oocytes with an IC₅₀ of 0.20 μM, causes voltage-dependent inhibition and a small positive shift in activation potential, and exhibits partial to nearly irreversible binding^[2].
ProTx-I (0.1-10 μM; ~2-7 min) weakly inhibits Ba²⁺ currents through hCav3.2-expressing Xenopus laevis oocytes with an IC₅₀ of 31.8 μM, does not alter channel activation properties, and exhibits fully reversible binding^[2].
ProTx-I (multiple concentrations) shows drastically reduced sensitivity when the domain IV S3-S4 linker of hCav3.1 is replaced with that of hCav3.2, resulting in an IC₅₀ of 17.8 μM in hCav3.1/S3S4-expressing Xenopus laevis oocytes^[2].
ProTx-I (multiple concentrations) shows increased sensitivity when the domain IV S3-S4 linker of hCav3.2 is replaced with that of hCav3.1, resulting in an IC₅₀ of 15.8 μM in hCav3.2/S3S4-expressing Xenopus laevis oocytes^[2].
ProTx-I (70 nM) inhibits heterologously expressed Cav3.1 voltage-gated calcium channels by shifting their voltage dependence of activation to more positive potentials, with an apparent IC₅₀ of 70 nM during weak depolarizations^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

3987.49

C₁₇₁H₂₄₅N₅₃O₄₇S₆

484598-35-8

Solid

white

Glu-Cys-Arg-Tyr-Trp-Leu-Gly-Gly-Cys-Ser-Ala-Gly-Gln-Thr-Cys-Cys-Lys-His-Leu-Val-Cys-Ser-Arg-Arg-His-Gly-Trp-Cys-Val-Trp-Asp-Gly-Thr-Phe-Ser (Disulfide bridge:Cys2-Cys16;Cys9-Cys21;Cys15-Cys28)

ECRYWLGGCSAGQTCCKHLVCSRRHGWCVWDGTFS (Disulfide bridge:Cys2-Cys16;Cys9-Cys21;Cys15-Cys28)

Room temperature in continental US; may vary elsewhere.

Sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

• [1]. Rupasinghe DB, et al. Mutational analysis of ProTx-I and the novel venom peptide Pe1b provide insight into residues responsible for selective inhibition of the analgesic drug target Na_V1.7. Biochem Pharmacol. 2020;181:114080.  [Content Brief]

  [2]. Ohkubo T, et al. Tarantula toxin ProTx-I differentiates between human T-type voltage-gated Ca2+ Channels Cav3.1 and Cav3.2. J Pharmacol Sci. 2010;112(4):452-458.  [Content Brief]

  [3]. Priest BT, et al. ProTx-I and ProTx-II: gating modifiers of voltage-gated sodium channels. Toxicon. 2007;49(2):194-201.