HC-030031

Biological Activity

HC-030031 is a TRPA1 selective antagonist. TRPA1 may play an important role in acute formalin and CFA induced pain. HC-030031 does not block currents mediated by TRPV1, TRPV3, TRPV4 hERG, or NaV1.2 channels. The selective TRPA1 antagonist HC-030031 can be used in cells or delivered to animals orally, by inhalation, or by injection. Oral administration of HC-030031 reduced AITC-induced nocifensive behaviors at a dose of 100 mg/kg in the rat. Moreover, oral HC-030031 (100 mg/kg) significantly reversed mechanical hypersensitivity in the more chronic models of Complete Freunds Adjuvant (CFA)-induced inflammatory pain and the spinal nerve ligation model of neuropathic pain.

Customer Product Validations & Biological Datas

	Source	Cancer Res (2013). Figure 1. HC-030031
	Method	i.g.
	Cell Lines	C57BL/6 mice
	Concentrations	300 mg/kg
	Incubation Time	60 minutes
	Results	Systemic treatment with HC-030031 (300 mg/kg, i.g.) at day 7 after treatment with bortezomib (0.2 or 0.5 mg/kg, i.p.) completely but transiently reverted both mechanical hyperalgesia and cold allodynia

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

Chemical Information

References

TRPA1 mediates mechanical sensitization in nociceptors during inflammation.
Lennertz RC, et al. PLoS One. 2012;7(8):e43597. PMID: 22927999.

HC-030031, a TRPA1 selective antagonist, attenuates inflammatory- and neuropathy-induced mechanical hypersensitivity.
Eid SR, et al. Mol Pain. 2008 Oct 27;4:48. PMID: 18954467.

TRPA1 mediates formalin-induced pain.
McNamara CR, et al. Proc Natl Acad Sci U S A. 2007 Aug 14;104(33):13525-30. PMID: 17686976.