Target Information
| Target General Information | Top | |||||
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| Target ID |
T32247
(Former ID: TTDS00485)
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| Target Name |
Calcitonin receptor (CALCR)
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| Synonyms |
CT-R
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| Gene Name |
CALCR
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Bone paget disease [ICD-11: FB85] | |||||
| 2 | Low bone mass disorder [ICD-11: FB83] | |||||
| Function |
The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. The calcitonin receptor is thought to couple to the heterotrimeric guanosine triphosphate-binding protein that is sensitive to cholera toxin. This is a receptor for calcitonin.
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| BioChemical Class |
GPCR secretin
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| UniProt ID | ||||||
| Sequence |
MRFTFTSRCLALFLLLNHPTPILPAFSNQTYPTIEPKPFLYVVGRKKMMDAQYKCYDRMQ
QLPAYQGEGPYCNRTWDGWLCWDDTPAGVLSYQFCPDYFPDFDPSEKVTKYCDEKGVWFK HPENNRTWSNYTMCNAFTPEKLKNAYVLYYLAIVGHSLSIFTLVISLGIFVFFRSLGCQR VTLHKNMFLTYILNSMIIIIHLVEVVPNGELVRRDPVSCKILHFFHQYMMACNYFWMLCE GIYLHTLIVVAVFTEKQRLRWYYLLGWGFPLVPTTIHAITRAVYFNDNCWLSVETHLLYI IHGPVMAALVVNFFFLLNIVRVLVTKMRETHEAESHMYLKAVKATMILVPLLGIQFVVFP WRPSNKMLGKIYDYVMHSLIHFQGFFVATIYCFCNNEVQTTVKRQWAQFKIQWNQRWGRR PSNRSARAAAAAAEAGDIPIYICHQEPRNEPANNQGEESAEIIPLNIIEQESSA Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T92CLX | |||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 2 Approved Drugs | + | ||||
| 1 | Calcitonin Human | Drug Info | Approved | Paget's disease | [2] | |
| 2 | Salmon Calcitonin | Drug Info | Approved | Osteoporosis | [3], [4] | |
| Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
| 1 | DACRA 089 | Drug Info | Phase 1 | Type 2 diabetes | [5] | |
| 2 | LY 3541105 | Drug Info | Phase 1 | Obesity | [6] | |
| Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
| 1 | TJN-220 | Drug Info | Terminated | Hypertension | [7] | |
| Mode of Action | [+] 4 Modes of Action | + | ||||
| Modulator | [+] 2 Modulator drugs | + | ||||
| 1 | Calcitonin Human | Drug Info | [8] | |||
| 2 | TJN-220 | Drug Info | [12] | |||
| Binder | [+] 1 Binder drugs | + | ||||
| 1 | Salmon Calcitonin | Drug Info | [1], [9] | |||
| Agonist | [+] 2 Agonist drugs | + | ||||
| 1 | DACRA 089 | Drug Info | [10] | |||
| 2 | LY 3541105 | Drug Info | [11] | |||
| Inhibitor | [+] 13 Inhibitor drugs | + | ||||
| 1 | CGNLSTCBLGTYTQDFNKFHZYPQTAIGVGAP-amide | Drug Info | [13] | |||
| 2 | CGNLSTCBLGTYTQDF[DKFHO]YPQTAIGVGAP-amide | Drug Info | [13] | |||
| 3 | CGNLSTCMLGTYTQDFc[DKFHK]FPQTAIGVGAP-amide | Drug Info | [13] | |||
| 4 | CGNLSTCMLGTYTQDFc[DKFHO]FPQTAIGVGAP-amide | Drug Info | [13] | |||
| 5 | CGNLSTCMLGTYTQDFNKFHTFPQTAIGVGAP-amide | Drug Info | [13] | |||
| 6 | CGNLSTCMLGTYTQDFNKPHTFPQTAIGVGAP-amide | Drug Info | [13] | |||
| 7 | CGNLSTCMLGTYTQDFNPFHTFPQTAIGVGAP-amide | Drug Info | [13] | |||
| 8 | CGNLSTCMLGTYTQDFNPKHTFPQTAIGVGAP-amide | Drug Info | [13] | |||
| 9 | CSNLSTCVLGKLSQELc[DKLHK]YPRTNTGSGTP-amide | Drug Info | [13] | |||
| 10 | CSNLSTCVLGKLSQELc[DKLHO]YPRTNTGSGTP-amide | Drug Info | [13] | |||
| 11 | CSNLSTCVLGKLSQELc[DKLQK]YPRTNTGSGTP-amide | Drug Info | [13] | |||
| 12 | CSNLSTCVLGKLSQELHKLQTYPRTNTGSGTP-amide | Drug Info | [13] | |||
| 13 | CSNLSTCVLGKLSQELNKLHBYPRTNTGSGTP-amide | Drug Info | [13] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: (2s)-2-{[(1r)-1-Hydroxyhexadecyl]oxy}-3-{[(1r)-1-Hydroxyoctadecyl]oxy}propyl 2-(Trimethylammonio)ethyl Phosphate | Ligand Info | |||||
| Structure Description | Calcitonin Receptor in complex with Gs and salmon calcitonin peptide | PDB:7TYN | ||||
| Method | Electron microscopy | Resolution | 2.60 Å | Mutation | Yes | [14] |
| PDB Sequence |
KPFLYVVGRK
46 KMMDAQYKCY56 DRMQQLPAYQ66 GEGPYCNRTW76 DGWLCWDDTP86 AGVLSYQFCP 96 DYFPDFDPSE106 KVTKYCDEKG116 VWFKHPENNR126 TWSNYTMCNA136 FTPEKLKNAY 146 VLYYLAIVGH156 SLSIFTLVIS166 LGIFVFFRSL176 GCQRVTLHKN186 MFLTYILNSM 196 IIIIHLVEVV206 PNGELVRRDP216 VSCKILHFFH226 QYMMACNYFW236 MLCEGIYLHT 246 LIVVAVFTEK256 QRLRWYYLLG266 WGFPLVPTTI276 HAITRAVYFN286 DNCWLSVETH 296 LLYIIHGPVM306 AALVVNFFFL316 LNIVRVLVTK326 MRETHEAESH336 MYLKAVKATM 346 ILVPLLGIQF356 VVFPWRPSNK366 MLGKIYDYVM376 HSLIHFQGFF386 VATIYCFCNN 396 EVQTTVKRQW406 AQF
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| Ligand Name: Cholesterol hemisuccinate | Ligand Info | |||||
| Structure Description | Calcitonin Receptor in complex with Gs and salmon calcitonin peptide | PDB:7TYN | ||||
| Method | Electron microscopy | Resolution | 2.60 Å | Mutation | Yes | [14] |
| PDB Sequence |
KPFLYVVGRK
46 KMMDAQYKCY56 DRMQQLPAYQ66 GEGPYCNRTW76 DGWLCWDDTP86 AGVLSYQFCP 96 DYFPDFDPSE106 KVTKYCDEKG116 VWFKHPENNR126 TWSNYTMCNA136 FTPEKLKNAY 146 VLYYLAIVGH156 SLSIFTLVIS166 LGIFVFFRSL176 GCQRVTLHKN186 MFLTYILNSM 196 IIIIHLVEVV206 PNGELVRRDP216 VSCKILHFFH226 QYMMACNYFW236 MLCEGIYLHT 246 LIVVAVFTEK256 QRLRWYYLLG266 WGFPLVPTTI276 HAITRAVYFN286 DNCWLSVETH 296 LLYIIHGPVM306 AALVVNFFFL316 LNIVRVLVTK326 MRETHEAESH336 MYLKAVKATM 346 ILVPLLGIQF356 VVFPWRPSNK366 MLGKIYDYVM376 HSLIHFQGFF386 VATIYCFCNN 396 EVQTTVKRQW406 AQF
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Pathway Affiliation
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Neuroactive ligand-receptor interaction | hsa04080 | Affiliated Target |
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| Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
| Osteoclast differentiation | hsa04380 | Affiliated Target |
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| Class: Organismal Systems => Development and regeneration | Pathway Hierarchy | ||
| Degree | 7 | Degree centrality | 7.52E-04 | Betweenness centrality | 2.59E-06 |
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| Closeness centrality | 1.72E-01 | Radiality | 1.27E+01 | Clustering coefficient | 5.24E-01 |
| Neighborhood connectivity | 6.86E+00 | Topological coefficient | 3.81E-01 | Eccentricity | 13 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 2 KEGG Pathways | + | ||||
| 1 | Neuroactive ligand-receptor interaction | |||||
| 2 | Osteoclast differentiation | |||||
| NetPath Pathway | [+] 1 NetPath Pathways | + | ||||
| 1 | RANKL Signaling Pathway | |||||
| Reactome | [+] 2 Reactome Pathways | + | ||||
| 1 | G alpha (s) signalling events | |||||
| 2 | Calcitonin-like ligand receptors | |||||
| WikiPathways | [+] 4 WikiPathways | + | ||||
| 1 | GPCRs, Class B Secretin-like | |||||
| 2 | RANKL/RANK Signaling Pathway | |||||
| 3 | GPCR ligand binding | |||||
| 4 | GPCR downstream signaling | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Improved absorption of salmon calcitonin by ultraflexible liposomes through intranasal delivery. Peptides. 2009 Jul;30(7):1288-95. | |||||
| REF 2 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 3 | URL: 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: 6973). | |||||
| REF 4 | Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. | |||||
| REF 5 | ClinicalTrials.gov (NCT03907202) A Clinical Study to Evaluate the Safety, Tolerability, PK, PD, and Efficacy of KBP-089 in Patients With T2DM. U.S. National Institutes of Health. | |||||
| REF 6 | ClinicalTrials.gov (NCT05380323) A Phase 1, Randomized, Placebo-Controlled, Dose-Escalation Study to Evaluate the Safety, Tolerability, and PK of LY3541105 Following Single Doses in Healthy/Overweight Participants and Multiple Doses in Overweight Participants. U.S.National Institutes of Health. | |||||
| REF 7 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002586) | |||||
| REF 8 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. | |||||
| REF 9 | Purification and characterization of calcitonin receptors in rat kidney membranes by covalent cross-linking techniques. Eur J Biochem. 1986 Feb 17;155(1):141-7. | |||||
| REF 10 | A novel dual amylin and calcitonin receptor agonist, KBP-089, induces weight loss through a reduction in fat, but not lean mass, while improving food preference. Br J Pharmacol. 2017 Apr;174(7):591-602. | |||||
| REF 11 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2023. Adis Insight | |||||
| REF 12 | Evaluation of the long-lasting antihypertensive action of 7-O-ethylfangchinoline. Jpn J Pharmacol. 1994 Sep;66(1):35-46. | |||||
| REF 13 | Side-chain lactam-bridge conformational constraints differentiate the activities of salmon and human calcitonins and reveal a new design concept fo... J Med Chem. 2002 Feb 28;45(5):1108-21. | |||||
| REF 14 | A structural basis for amylin receptor phenotype. Science. 2022 Mar 25;375(6587):eabm9609. | |||||
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