Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTLDPRG)

• DTT Name: Guanylyl cyclase C (GUCY2C)
• Synonyms: hSTAR; STA receptor; Intestinal guanylate cyclase; Heat-stable enterotoxin receptor; GUC2C; GC-C
• Gene Name: GUCY2C
• DTT Type: Successful target; [1]
• BioChemical Class: Phosphorus-oxygen lyase
• UniProt ID: GUC2C_HUMAN
• TTD ID: T97947
• EC Number: EC 4.6.1.2
• Sequence:
  MKTLLLDLALWSLLFQPGWLSFSSQVSQNCHNGSYEISVLMMGNSAFAEPLKNLEDAVNE
  GLEIVRGRLQNAGLNVTVNATFMYSDGLIHNSGDCRSSTCEGLDLLRKISNAQRMGCVLI
  GPSCTYSTFQMYLDTELSYPMISAGSFGLSCDYKETLTRLMSPARKLMYFLVNFWKTNDL
  PFKTYSWSTSYVYKNGTETEDCFWYLNALEASVSYFSHELGFKVVLRQDKEFQDILMDHN
  RKSNVIIMCGGPEFLYKLKGDRAVAEDIVIILVDLFNDQYFEDNVTAPDYMKNVLVLTLS
  PGNSLLNSSFSRNLSPTKRDFALAYLNGILLFGHMLKIFLENGENITTPKFAHAFRNLTF
  EGYDGPVTLDDWGDVDSTMVLLYTSVDTKKYKVLLTYDTHVNKTYPVDMSPTFTWKNSKL
  PNDITGRGPQILMIAVFTLTGAVVLLLLVALLMLRKYRKDYELRQKKWSHIPPENIFPLE
  TNETNHVSLKIDDDKRRDTIQRLRQCKYDKKRVILKDLKHNDGNFTEKQKIELNKLLQID
  YYNLTKFYGTVKLDTMIFGVIEYCERGSLREVLNDTISYPDGTFMDWEFKISVLYDIAKG
  MSYLHSSKTEVHGRLKSTNCVVDSRMVVKITDFGCNSILPPKKDLWTAPEHLRQANISQK
  GDVYSYGIIAQEIILRKETFYTLSCRDRNEKIFRVENSNGMKPFRPDLFLETAEEKELEV
  YLLVKNCWEEDPEKRPDFKKIETTLAKIFGLFHDQKNESYMDTLIRRLQLYSRNLEHLVE
  ERTQLYKAERDRADRLNFMLLPRLVVKSLKEKGFVEPELYEEVTIYFSDIVGFTTICKYS
  TPMEVVDMLNDIYKSFDHIVDHHDVYKVETIGDAYMVASGLPKRNGNRHAIDIAKMALEI
  LSFMGTFELEHLPGLPIWIRIGVHSGPCAAGVVGIKMPRYCLFGDTVNTASRMESTGLPL
  RIHVSGSTIAILKRTECQFLYEVRGETYLKGRGNETTYWLTGMKDQKFNLPTPPTVENQQ
  RLQAEFSDMIANSLQKRQAAGIRSQKPRRVASYKKGTLEYLQLNTTDKESTYF
• 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.
• KEGG Pathway:
  Purine metabolism (hsa00230)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  Intestinal infectious diseases (R-HSA-8942233)
  Digestion (R-HSA-8935690)

Molecular Interaction Atlas (MIA) of This DTT

3 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Linaclotide	DM4EGV0	Irritable bowel syndrome	DD91.0	Approved	[1]
MD-1100	DM4IAKR	Constipation	DD91.1	Approved	[2]
Plecanatide	DMKEX7O	Chronic idiopathic constipation	DC32	Approved	[3]

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
MLN0264	DMI4E9K	Gastrointestinal cancer	2C11	Phase 2	[4]
SP-333	DM2UKJV	Ulcerative colitis	DD71	Phase 2	[5]
PF-07062119	DME3BJL	Solid tumour/cancer	2A00-2F9Z	Phase 1	[6]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Gastric cancer	2C82	Gastric tissue	9.52E-03	2.35	5.13
Irritable bowel syndrome	DD91.0	Rectal colon tissue	2.18E-02	-0.31	-0.55

References

• [1] Emerging drugs for postoperative ileus. Expert Opin Emerg Drugs. 2007 Nov;12(4):619-26.
• [2] Emerging drugs for irritable bowel syndrome. Expert Opin Emerg Drugs. 2006 May;11(2):293-313.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [4] J Clin Oncol 31, 2013 (suppl; abstr TPS3646).
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] 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.