HC-030031 is a selective inhibitor of transient receptor potential ankyrin subfamily member 1 (TRPA1). HC-030031 blocks calcium influx in cells, with IC50 values of 4.9±0.1 and 7.5±0.2μM for calcium influx induced by cinnamaldehyde and allyl isothiocyanate (AITC), respectively[1-2].
In HEK293 cells expressing TRPA1, HC-030031 (10μM) rapidly and reversibly blocks inward and outward currents induced by AITC or formalin, but has no effect on currents mediated by TRPV1, TRPV3, TRPV4, hERG, or NaV1.2 channels[2]. Blocking TRPA1 with HC-030031 (10μM) inhibited apoptosis of HEK293 cells, reduced the levels of IL-1β, IL-6, TNF-α and INF-γ, and reduced the levels of cleaved-cas3, cleaved-PARP and iNOS[3].
HC-030031 at a dose of 100mg/kg reduced the pain response behavior of mice in the AITC-induced pain model. Oral HC-030031 (100mg/kg) significantly reversed mechanical hypersensitivity in a more chronic, fully Fredrick-adjuvant (CFA) -induced model of inflammatory pain and a spinal nerve ligation model of neuropathic pain[1]. In formalin-induced pain behavior in rats, HC-030031 (30, 100, and 300mg/kg) reduced the number of flinching events in a dose-dependent manner, and at the 300mg/kg dose, the number of flinching events was reduced to a level similar to that of saline injection[2].
References:
[1] Eid S R, Crown E D, Moore E L, et al. HC-030031, a TRPA1 selective antagonist, attenuates inflammatory-and neuropathy-induced mechanical hypersensitivity[J]. Molecular pain, 2008, 4: 1744-8069-4-48.
[2] McNamara CR, Mandel-Brehm J, Bautista DM, Siemens J, Deranian KL, Zhao M, Hayward NJ, Chong JA, Julius D, Moran MM, Fanger CM. TRPA1 mediates formalin-induced pain. Proc Natl Acad Sci U S A. 2007 Aug 14;104(33):13525-30.
[3] Yuan J, Liang X, Zhou W, Feng J, Wang Z, Shen S, Guan X, Zhao L, Deng F. TRPA1 promotes cisplatin-induced nephrotoxicity through inflammation mediated by the MAPK/NF-κB signaling pathway. Ann Transl Med. 2021 Oct;9(20):1578.
HC-030031是瞬时受体电位锚蛋白亚家族成员1（TRPA1）的选择性抑制剂。HC-030031可阻断细胞的钙流入，对肉桂醛和异硫氰酸烯丙酯（AITC）诱导的钙内流的IC50 值分别为4.9±0.1和7.5±0.2μM[1-2]。
在表达TRPA1的HEK293细胞中，HC-030031（10μM）能够迅速且可逆地阻断由AITC或福尔马林引起的向内和向外的电流，对TRPV1、TRPV3、TRPV4、hERG或NaV1.2 通道介导的电流没有阻断作用[2]。HC-030031（10μM）阻断TRPA1可抑制HEK293细胞凋亡，降低IL-1β、IL-6、TNF-α和INF-γ水平，降低cleaved-cas3、cleaved-PARP和iNOS水平[3]。
HC-030031在100mg/kg的剂量下降低了AITC诱导的疼痛模型中小鼠的疼痛反应行为。在更慢性的完全弗氏佐剂（CFA）诱导的炎症性疼痛模型和神经性疼痛的脊神经结扎模型中口服HC-030031（100mg/kg）显着逆转了机械超敏反应[1]。在福尔马林诱发的大鼠疼痛行为中，HC-030031（30、100和300mg/kg）以剂量依赖性方式减少了退缩数量，并且在300mg/kg剂量时退缩数量降低到与生理盐水注射相似的水平[2]。