BCTC

Biological Activity

BCTC is a orally effective vanilloid receptor 1 (TRPV1 receptor) antagonist. BCTC is also a potent and specific inhibitor of transient receptor potential cation channel subfamily M member 8 (TRPM8) in prostate cancer (PCa) DU145 cells. BCTC inhibits acid- and capsaicin-induced activation of rat TRPV1 receptors (IC₅₀ values are 6.0 and 35 nM respectively). BCTC displays analgesic properties in rat models of inflammatory and neuropathic pain.

Protocol

Cell Experiment
Cell lines
Preparation method
Concentrations
Incubation time

Animal Experiment
Animal models	Jugular-cannulated male Sprague-Dawley rats (200-300 g)
Formulation	using 25% hydroxypropyl-β-cyclodextrin as vehicle
Dosages	3, 10, and 40 mg/kg p.o. or 3 mg/kg i.v.
Administration	p.o. or i.v.

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

Anti-tumor activity of the TRPM8 inhibitor BCTC in prostate cancer DU145 cells
Tao Liu, et al. Oncol Lett. 2016 Jan;11(1):182-188. PMID: 26870186.

N-(4-tertiarybutylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine -1(2H)-carbox-amide (BCTC), a novel, orally effective vanilloid receptor 1 antagonist with analgesic properties: I. in vitro characterization and pharmacokinetic properties
Kenneth J Valenzano, et al. J Pharmacol Exp Ther. 2003 Jul;306(1):377-86. PMID: 12721338.

Activity of cytisine and its brominated isoteres on recombinant human α7, α4β2 and α4β4 nicotinic acetylcholine receptors.
Houlihan, et al. J Neurochem. 2001;78: 1029. PMID: 11553677.