Target Information

Target General Infomation
Target ID
T32262
Former ID
TTDC00093
Target Name
Calcitoningene-related peptide type 1 receptor
Gene Name
CALCRL
Synonyms
CGRP receptor 1; CGRP type 1 receptor; Calcitoningene-related peptide 1 receptor; Calcitoninreceptor-like receptor; CALCRL
Target Type
Clinical Trial
Disease Migraine [ICD9: 346; ICD10: G43]
Migraine; Cluster headaches [ICD9: 339.00, 339.01, 339.02, 346; ICD10: G43, G44.0]
Function
Receptor for calcitonin-gene-related peptide (CGRP) together with RAMP1 and receptor for adrenomedullin together with RAMP3 (By similarity). Receptor for adrenomedullin together with RAMP2. The activity of thisreceptor is mediated by G proteins which activate adenylyl cyclase.
BioChemical Class
GPCR secretin
Target Validation
T32262
UniProt ID
Q16602
Sequence
MEKKCTLNFLVLLPFFMILVTAELEESPEDSIQLGVTRNKIMTAQYECYQKIMQDPIQQA
EGVYCNRTWDGWLCWNDVAAGTESMQLCPDYFQDFDPSEKVTKICDQDGNWFRHPASNRT
WTNYTQCNVNTHEKVKTALNLFYLTIIGHGLSIASLLISLGIFFYFKSLSCQRITLHKNL
FFSFVCNSVVTIIHLTAVANNQALVATNPVSCKVSQFIHLYLMGCNYFWMLCEGIYLHTL
IVVAVFAEKQHLMWYYFLGWGFPLIPACIHAIARSLYYNDNCWISSDTHLLYIIHGPICA
ALLVNLFFLLNIVRVLITKLKVTHQAESNLYMKAVRATLILVPLLGIEFVLIPWRPEGKI
AEEVYDYIMHILMHFQGLLVSTIFCFFNGEVQAILRRNWNQYKIQFGNSFSNSEALRSAS
YTVSTISDGPGYSHDCPSEHLNGKSIHDIENVLLKPENLYN
Structure
3AQF; 3N7P; 3N7R; 3N7S
Drugs and Mode of Action
Drug(s) AMG 334 Drug Info Phase 2 Migraine [524809]
BI-44370 TA Drug Info Phase 2 Migraine [522435]
BMS-927711 Drug Info Phase 2 Migraine [523614]
MK-3207 Drug Info Phase 2 Migraine [522371]
Olcegepant Drug Info Phase 2 Migraine [524842], [542045]
Telcagepant Drug Info Phase 2 Migraine; Cluster headaches [531970], [542049]
LBR-101 Drug Info Phase 1 Migraine [532603]
Modulator AMG 334 Drug Info [544443]
Olcegepant Drug Info
Antagonist BI-44370 TA Drug Info [531309]
BMS-927711 Drug Info [532462]
MK-3207 Drug Info [530631]
Telcagepant Drug Info [537202], [537267], [537377]
Inhibitor BMS-694153 Drug Info [529618]
EPIMER A Drug Info [530247]
FV-Aib-TDVGPFAF Drug Info [527974]
FV-Hyp-TDVGPFAF Drug Info [527974]
FV-Tic-TDVGPFAF Drug Info [527974]
FVATDVGPFAF Drug Info [527974]
FVPTDVG-Tic-FAF-Tic Drug Info [527974]
FVPTDVGAFAF Drug Info [527974]
FVPTDVGPFAF Drug Info [527974]
HCGRPalpha Drug Info [529789]
ISOMER A Drug Info [530247]
Pathways
KEGG Pathway Neuroactive ligand-receptor interaction
Vascular smooth muscle contraction
Reactome G alpha (s) signalling events
Calcitonin-like ligand receptors
WikiPathways GPCRs, Class B Secretin-like
Endothelin Pathways
GPCR ligand binding
GPCR downstream signaling
References
Ref 522371ClinicalTrials.gov (NCT00712725) MK3207 for Treatment of Acute Migraines (3207-005). U.S. National Institutes of Health.
Ref 522435ClinicalTrials.gov (NCT00751803) BI 44370 TA in Acute Migraine Attack. U.S. National Institutes of Health.
Ref 523614ClinicalTrials.gov (NCT01430442) Dose Ranging Study of a Drug for the Treatment of Acute Migraine. U.S. National Institutes of Health.
Ref 524809ClinicalTrials.gov (NCT02174861) A Study to Assess the Long-term Safety and Efficacy of AMG 334 in Chronic Migraine Prevention.. U.S. National Institutes of Health.
Ref 524842ClinicalTrials.gov (NCT02198339) Efficacy, Safety, Tolerability and Pharmacokinetics of BIBN 4096 BS Versus Placebo in the Treatment of a Single Attack of Acute Migraine Headache. U.S. National Institutes of Health.
Ref 531970ACS chemical neuroscience molecule spotlight on Telcagepant (MK-0974). ACS Chem Neurosci. 2011 Jul 20;2(7):334-5.
Ref 532603Safety and tolerability of LBR-101, a humanized monoclonal antibody that blocks the binding of CGRP to its receptor: Results of the Phase 1 program. Cephalalgia. 2013 Dec 23;34(7):483-492.
Ref 542045(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 702).
Ref 542049(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 703).
Ref 527974J Med Chem. 2006 Jan 26;49(2):616-24.Identification of the key residue of calcitonin gene related peptide (CGRP) 27-37 to obtain antagonists with picomolar affinity at the CGRP receptor.
Ref 529618J Med Chem. 2008 Aug 28;51(16):4858-61. Epub 2008 Jul 30.Discovery of (R)-4-(8-fluoro-2-oxo-1,2-dihydroquinazolin-3(4H)-yl)-N-(3-(7-methyl-1H-indazol-5-yl)-1-oxo-1-(4-(piperidin-1-yl)piperidin-1-yl)propan-2-yl)piperidine-1-carboxamide (BMS-694153): a potent antagonist of the human calcitonin gene-related peptide receptor for migraine with rapid and efficient intranasal exposure.
Ref 529789J Med Chem. 2008 Nov 27;51(22):7094-8.cis-4-(Piperazin-1-yl)-5,6,7a,8,9,10,11,11a-octahydrobenzofuro[2,3-h]quinazolin-2-amine (A-987306), a new histamine H4R antagonist that blocks pain responses against carrageenan-induced hyperalgesia.
Ref 530247Bioorg Med Chem Lett. 2009 Aug 15;19(16):4740-2. Epub 2009 Jun 17.The identification of potent, orally bioavailable tricyclic CGRP receptor antagonists.
Ref 530631J Pharmacol Exp Ther. 2010 Apr;333(1):152-60. Epub 2010 Jan 11.Pharmacological properties of MK-3207, a potent and orally active calcitonin gene-related peptide receptor antagonist.
Ref 531309BI 44370 TA, an oral CGRP antagonist for the treatment of acute migraine attacks: results from a phase II study. Cephalalgia. 2011 Apr;31(5):573-84.
Ref 532462BMS-927711 for the acute treatment of migraine: a double-blind, randomized, placebo controlled, dose-ranging trial. Cephalalgia. 2014 Feb;34(2):114-25.
Ref 532603Safety and tolerability of LBR-101, a humanized monoclonal antibody that blocks the binding of CGRP to its receptor: Results of the Phase 1 program. Cephalalgia. 2013 Dec 23;34(7):483-492.
Ref 537202A flexible and high throughput liquid chromatography-tandem mass spectrometric assay for the quantitation of telcagepant in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2009 May 15;877(14-15):1465-71. Epub 2009 Mar 18.
Ref 537267Elimination of diastereomer interference to determine Telcagepant (MK-0974) in human plasma using on-line turbulent-flow technology and off-line solid-phase extraction coupled with liquid chromatography/tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Jun 1;877(16-17):1634-42. Epub 2009 Apr 8.
Ref 537377CGRP antagonists: novel concept for treatment of migraine. Med Monatsschr Pharm. 2009 May;32(5):182-5.
Ref 544443EHMTI-0315. AMG 334, the first potent and selective human monoclonal antibody antagonist against the CGRP receptor. J Headache Pain. 2014; 15(Suppl 1): G43.

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