Target Information
| Target General Information | Top | |||||
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| Target ID |
T97947
(Former ID: TTDC00171)
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| Target Name |
Guanylyl cyclase C (GUCY2C)
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| Synonyms |
hSTAR; STA receptor; Intestinal guanylate cyclase; Heat-stable enterotoxin receptor; GUC2C; GC-C
Click to Show/Hide
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| Gene Name |
GUCY2C
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Chronic pancreatitis [ICD-11: DC32] | |||||
| 2 | Irritable bowel syndrome [ICD-11: DD91] | |||||
| Function |
Receptor for the E.coli heat-stable enterotoxin (E.coli enterotoxin markedly stimulates the accumulation of cGMP in mammalian cells expressing GC-C). Also activated by the endogenous peptides guanylin and uroguanylin.
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| BioChemical Class |
Phosphorus-oxygen lyase
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| UniProt ID | ||||||
| EC Number |
EC 4.6.1.2
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| Sequence |
MKTLLLDLALWSLLFQPGWLSFSSQVSQNCHNGSYEISVLMMGNSAFAEPLKNLEDAVNE
GLEIVRGRLQNAGLNVTVNATFMYSDGLIHNSGDCRSSTCEGLDLLRKISNAQRMGCVLI GPSCTYSTFQMYLDTELSYPMISAGSFGLSCDYKETLTRLMSPARKLMYFLVNFWKTNDL PFKTYSWSTSYVYKNGTETEDCFWYLNALEASVSYFSHELGFKVVLRQDKEFQDILMDHN RKSNVIIMCGGPEFLYKLKGDRAVAEDIVIILVDLFNDQYFEDNVTAPDYMKNVLVLTLS PGNSLLNSSFSRNLSPTKRDFALAYLNGILLFGHMLKIFLENGENITTPKFAHAFRNLTF EGYDGPVTLDDWGDVDSTMVLLYTSVDTKKYKVLLTYDTHVNKTYPVDMSPTFTWKNSKL PNDITGRGPQILMIAVFTLTGAVVLLLLVALLMLRKYRKDYELRQKKWSHIPPENIFPLE TNETNHVSLKIDDDKRRDTIQRLRQCKYDKKRVILKDLKHNDGNFTEKQKIELNKLLQID YYNLTKFYGTVKLDTMIFGVIEYCERGSLREVLNDTISYPDGTFMDWEFKISVLYDIAKG MSYLHSSKTEVHGRLKSTNCVVDSRMVVKITDFGCNSILPPKKDLWTAPEHLRQANISQK GDVYSYGIIAQEIILRKETFYTLSCRDRNEKIFRVENSNGMKPFRPDLFLETAEEKELEV YLLVKNCWEEDPEKRPDFKKIETTLAKIFGLFHDQKNESYMDTLIRRLQLYSRNLEHLVE ERTQLYKAERDRADRLNFMLLPRLVVKSLKEKGFVEPELYEEVTIYFSDIVGFTTICKYS TPMEVVDMLNDIYKSFDHIVDHHDVYKVETIGDAYMVASGLPKRNGNRHAIDIAKMALEI LSFMGTFELEHLPGLPIWIRIGVHSGPCAAGVVGIKMPRYCLFGDTVNTASRMESTGLPL RIHVSGSTIAILKRTECQFLYEVRGETYLKGRGNETTYWLTGMKDQKFNLPTPPTVENQQ RLQAEFSDMIANSLQKRQAAGIRSQKPRRVASYKKGTLEYLQLNTTDKESTYF Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 3 Approved Drugs | + | ||||
| 1 | Linaclotide | Drug Info | Approved | Irritable bowel syndrome | [1], [2] | |
| 2 | MD-1100 | Drug Info | Approved | Constipation | [3] | |
| 3 | Plecanatide | Drug Info | Approved | Irritable bowel syndrome | [4] | |
| Clinical Trial Drug(s) | [+] 3 Clinical Trial Drugs | + | ||||
| 1 | MLN0264 | Drug Info | Phase 2 | Gastrointestinal cancer | [5] | |
| 2 | SP-333 | Drug Info | Phase 2 | Ulcerative colitis | [6] | |
| 3 | PF-07062119 | Drug Info | Phase 1 | Solid tumour/cancer | [7] | |
| Mode of Action | [+] 4 Modes of Action | + | ||||
| Activator | [+] 2 Activator drugs | + | ||||
| 1 | Linaclotide | Drug Info | [1] | |||
| 2 | MD-1100 | Drug Info | [8] | |||
| Modulator | [+] 2 Modulator drugs | + | ||||
| 1 | Plecanatide | Drug Info | [9] | |||
| 2 | MLN0264 | Drug Info | [10] | |||
| Agonist | [+] 1 Agonist drugs | + | ||||
| 1 | SP-333 | Drug Info | [11] | |||
| Inhibitor | [+] 1 Inhibitor drugs | + | ||||
| 1 | PF-07062119 | Drug Info | [12] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| 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 Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
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 Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Purine metabolism | hsa00230 | Affiliated Target |
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| Class: Metabolism => Nucleotide metabolism | Pathway Hierarchy | ||
| Degree | 2 | Degree centrality | 2.15E-04 | Betweenness centrality | 2.02E-04 |
|---|---|---|---|---|---|
| Closeness centrality | 1.20E-01 | Radiality | 1.05E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 1.50E+00 | Topological coefficient | 5.00E-01 | Eccentricity | 15 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Emerging drugs for postoperative ileus. Expert Opin Emerg Drugs. 2007 Nov;12(4):619-26. | |||||
| REF 2 | 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: 5017). | |||||
| REF 3 | Nat Rev Drug Discov. 2013 Feb;12(2):87-90. | |||||
| REF 4 | 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85. | |||||
| REF 5 | ClinicalTrials.gov (NCT02202759) A Study of MLN0264 in Patients With Cancer of the Stomach or Gastroesophageal Junction. U.S. National Institutes of Health. | |||||
| REF 6 | ClinicalTrials.gov (NCT01983306) Dose-ranging Study to Assess Safety and Efficacy of SP-333 for the Treatment of Opioid-induced Constipation (OIC). U.S. National Institutes of Health. | |||||
| REF 7 | ClinicalTrials.gov (NCT04171141) Study to Test the Safety and Tolerability of PF-07062119 in Patients With Selected Advanced or Metastatic Gastrointestinal Tumors.. U.S. National Institutes of Health. | |||||
| REF 8 | Emerging drugs for irritable bowel syndrome. Expert Opin Emerg Drugs. 2006 May;11(2):293-313. | |||||
| REF 9 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. | |||||
| REF 10 | J Clin Oncol 31, 2013 (suppl; abstr TPS3646). | |||||
| REF 11 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 12 | Discovery and optimization of a novel anti-GUCY2c x CD3 bispecific antibody for the treatment of solid tumors. MAbs. Jan-Dec 2021;13(1):1850395. | |||||
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