Target Validation Information
TTD ID	T32262
Target Name	Calcitonin gene-related peptide receptor (CGRPR)
Type of Target	Successful
Drug Potency against Target	Telcagepant	Drug Info	IC50 = 10.9 nM	[3]
	EPIMER A	Drug Info	IC50 = 24 nM	[2]
	FVATDVGPFAF	Drug Info	Ki = 8.4 nM	[1]
	FVPTDVG-Tic-FAF-Tic	Drug Info	Ki = 1.8 nM	[1]
	FVPTDVGAFAF	Drug Info	Ki = 13.6 nM	[1]
	ISOMER A	Drug Info	IC50 = 6.5 nM	[2]
Action against Disease Model	Telcagepant	Drug Info	In vitro, MK-0974 is a potent antagonist of the h uMan (K(i) = 0.77 nM) and rhesus (K(i) = 1.2 nM) CGRP receptors but displays >1500-fold lower affinity for the canine and rat receptors as determined via (125)I-h uMan CGRP competition binding assays. A rhesus pharmacodynamic assay measuring capsaicin-induced changes in forearm dermal blood flow via laser Doppler imaging was utilized to determine the in vivo activity of CGRP receptor antagonism. MK-0974 produced a concentration-dependent inhibition of dermal vasodilation, generated by capsaicin-induced release of endogenous CGRP, with plasma concentrations of 127 and 994 nM required to block 50 and 90% of the blood flow increase, respectively.	[4]
References
REF 1	Identification of the key residue of calcitonin gene related peptide (CGRP) 27-37 to obtain antagonists with picomolar affinity at the CGRP receptor. J Med Chem. 2006 Jan 26;49(2):616-24.
REF 2	The identification of potent, orally bioavailable tricyclic CGRP receptor antagonists. Bioorg Med Chem Lett. 2009 Aug 15;19(16):4740-2.
REF 3	Pharmacological properties of MK-3207, a potent and orally active calcitonin gene-related peptide receptor antagonist. J Pharmacol Exp Ther. 2010 Apr;333(1):152-60.
REF 4	Pharmacological characterization of MK-0974 [N-[(3R,6S)-6-(2,3-difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-i... J Pharmacol Exp Ther. 2008 Feb;324(2):416-21.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.