同义名 :	TRPM8 Antagonist
	CAS号 :	259674-19-6
	货号 :	A1176853
	分子式 :	C26H26N2O2
	纯度 :	98%+
	分子量 :	398.5
	MDL号 :	MFCD31746884
	存储条件：	Pure form Inert atmosphere, 2-8°C In solvent -20°C:3-6个月-80°C:12个月
	溶解度 :	-
	动物实验配方：

生物活性

描述

TRPM8 antagonist 14 is an effective selective TRPM8 antagonist with IC50 of 0.2 nm, which is used in the study of neuropathic pain syndrome. TRPM8 antagonist can effectively inhibit the increase of intracellular Ca2 + level induced by menthol in HEK293 cells stably expressing TRPM8 channel rat isoforms (ic50,40nm). RPM8 antagonist (1,10 and 30 mg / kg, s.c.) showed significant antinociceptive activity in a dose-dependent manner and inhibited wet dog milkshake (WDS) - like cold hypersensitivity in mice by 63% at 30 mg / kg. In addition, TRPM8 antagonist (0.1 and 1 μ g, s.c.) objective to alleviate the cold pain induced by oxaliplatin (oxp) in mice[2]. In the wet dog shakes (WDS) assay, compound 14 (TRPM8 antagonist 14) dose-dependently blocks icilin-triggered shaking behaviors in mice. Upon local administration, compound 14 dose dependently inhibits cold allodynia evoked by the chemotherapy oxaliplatin in a murine model of peripheral neuropathy at microgram doses[3].

实验方案
	1mg	5mg	10mg
1 mM 5 mM 10 mM	2.51mL 0.50mL 0.25mL	12.55mL 2.51mL 1.25mL	25.09mL 5.02mL 2.51mL

参考文献

[1]Bertamino A, Iraci N, Ostacolo C, et al. Identification of a Potent Tryptophan-Based TRPM8 Antagonist With in Vivo Analgesic Activity. J Med Chem. 2018;61(14):6140-6152. doi:10.1021/acs.jmedchem.8b00545 [2]Bertamino A, Iraci N, Ostacolo C, Ambrosino P, Musella S, Di Sarno V, Ciaglia T, Pepe G, Sala M, Soldovieri MV, Mosca I, Gonzalez-Rodriguez S, Fernandez-Carvajal A, Ferrer-Montiel A, Novellino E, Taglialatela M, Campiglia P, Gomez-Monterrey I. Identification of a Potent Tryptophan-Based TRPM8 Antagonist With in Vivo Analgesic Activity. J Med Chem. 2018 Jul 26;61(14):6140-6152 [3]Journigan VB, Feng Z, Rahman S, Wang Y, Amin ARMR, Heffner CE, Bachtel N, Wang S, Gonzalez-Rodriguez S, Fernández-Carvajal A, Fernández-Ballester G, Hilton JK, Van Horn WD, Ferrer-Montiel A, Xie XQ, Rahman T. Structure-Based Design of Novel Biphenyl Amide Antagonists of Human Transient Receptor Potential Cation Channel Subfamily M Member 8 Channels with Potential Implications in the Treatment of Sensory Neuropathies. ACS Chem Neurosci. 2020 Feb 5;11(3):268-290