HC-030031_product_DataBase

Bioactivity

HC-030031 is a potent and selective TRPA1 inhibitor, which antagonizes AITC- and formalin-evoked calcium influx with IC50s of 6.2±0.2 and 5.3±0.2 μM, respectively.

Target

TRPA1

Invitro

HC-030031 reversibly blocks TRPA1 currents with a similar potency, regardless of the agonist used; this includes blockade of currents elicited by reversible agonists, such as AITC, or irreversible agonists, such as N-methyl maleimide. HC-030031 blocks activation of TRPA1 by N-methyl maleimide, which opens the channel irreversibly through cysteine modification. HC-030031 does not block currents mediated by TRPV1, TRPV3, TRPV4, hERG, or NaV1.2 channels[1]. The potencies of HC-030031 versus cinnamaldehyde or allyl isothiocyanate (AITC or Mustard oil)-induced TRPA1 activation are 4.9±0.1 and 7.5±0.2 μM respectively (IC50). These findings are similar to the previously reported IC50 of 6.2 μM against AITC activation of TRPA1. The ability of HC-030031 to block TRPA1 activation is tested in a FLIPR calcium-influx assay using HEK-293 cells stably expressing human TRPA1. Concentrations of HC-030031 from 0.3 to 60 μM are incubated with cells for 10 minutes prior to addition of an EC60 concentration of either cinnamaldehyde or AITC. HC-030031 dose-dependently blocks cinnamaldehyde- and AITC-induced calcium influx with IC50 values of 4.9 and 7.5 μM, respectively[2].

In Vivo

After injection of AITC (50 μL of 10%) into the rat hind paw, HC-030031 (300 mg/kg) significantly reduces flinching during the first 5 min. Over the remainder of the hour, HC-030031 decreases flinch frequency, a result that mirrors the effects observed on formalin-induced flinching[1]. In the rat, oral administration of HC-030031 reduces AITC-induced nocifensive behaviors at a dose of 100 mg/kg. Moreover, oral HC-030031 (100 mg/kg) significantly reverses mechanical hypersensitivity in the more chronic models of Complete Freunds Adjuvant (CFA)-induced inflammatory pain and the spinal nerve ligation model of neuropathic pain. One hour post-oral administration, HC-030031 significantly reduces the lifting duration following 1% AITC injection (p<0.001)[2]. HC-030031 completely reverses the enhanced mechanical firing in inflamed mice (p<0.001)[3].

Name

HC-030031

CAS

349085-38-7

Formula

C18H21N5O3

Molar Mass

355.39

Appearance

Solid

Transport

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Reference

[1]. McNamara CR, et al. TRPA1 mediates formalin-induced pain. Proc Natl Acad Sci U S A. 2007 Aug 14;104(33):13525-30. [2]. Eid SR, et al. HC-030031, a TRPA1 selective antagonist, attenuates inflammatory- and neuropathy-induced mechanical hypersensitivity. Mol Pain. 2008 Oct 27;4:48. [3]. Lennertz RC, et al. TRPA1 mediates mechanical sensitization in nociceptors during inflammation. PLoS One. 2012;7(8):e43597. [4]. Miyake T, et al. Cold sensitivity of TRPA1 is unveiled by the prolyl hydroxylation blockade-induced sensitization to ROS. Nat Commun. 2016 Sep 15;7:12840. [5]. So K, et al. Hypoxia-induced sensitisation of TRPA1 in painful dysesthesia evoked by transient hindlimb ischemia/reperfusion in mice. Sci Rep. 2016 Mar 17;6:23261.

PeptideDB

HC-030031

CAS: 349085-38-7 F: C18H21N5O3 W: 355.39