Protein / target

Guanylyl cyclase C

Encoded byGUCY2CP25092Homo sapiensSwiss-Prot

UniProt: P25092 Ensembl: ENSG00000070019 HGNC: HGNC:4688 NCBI Gene: 2984

Clinically validated

Therapeutic maturity

Approved medicines

Open Targets target-level

View by indication →

Clinical trials

Small-molecule tractable

Druggability

Structure with Ligand

Protein at a glance

Biological role

Guanylate cyclase

Strongest disease association

Irritable Bowel Syndrome

Via encoding gene GUCY2C · Clinical evidence · score 0.58

Therapeutic position

Established drug target

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Guanylyl cyclase that catalyzes synthesis of cyclic GMP (cGMP) from GTP.

View complete UniProt function annotation

Guanylyl cyclase that catalyzes synthesis of cyclic GMP (cGMP) from GTP (PubMed:11950846, PubMed:1718270, PubMed:22436048, PubMed:22521417, PubMed:23269669). Receptor for the E.coli heat-stable enterotoxin; E.coli enterotoxin markedly stimulates the accumulation of cGMP in mammalian cells expressing GUCY2C (PubMed:1680854, PubMed:1718270). Also activated by the endogenous peptides guanylin and uroguanylin (PubMed:8381596)

Subcellular location

Cell membraneEndoplasmic reticulum membrane

Domains and Gene Ontology detail (13)

Domains & features

Protein kinaseGuanylate cyclase

Gene Ontology

Cendoplasmic reticulum membrane
Cplasma membrane
FATP binding
FGTP binding
Fguanylate cyclase activity
Fpeptide receptor activity
Fprotein kinase activity
Ftoxic substance binding
PcGMP biosynthetic process
Pintracellular signal transduction
Preceptor guanylyl cyclase signaling pathway

1073 aa · 123 kDa

Approved medicines with mapped indications

2 medicines · 2 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Constipation2 medicines

linaclotide plecanatide

Irritable Bowel Syndrome1 medicine

linaclotide

Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

linaclotide

Narrow target profileApprovedAgonist

Heat-stable enterotoxin receptor agonist

Indicated for Constipation, Irritable Bowel Syndrome

Direct interaction with this protein · Only this protein recorded as a target

plecanatide

Narrow target profileApprovedAgonist

Heat-stable enterotoxin receptor agonist

Indicated for Constipation

Direct interaction with this protein · Only this protein recorded as a target

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene GUCY2C

Gene-level evidence surfaced through the gene GUCY2C that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Irritable Bowel Syndrome

0.72Moderately supported

Clinical evidence dominant · Open Targets 0.58

Constipation

0.62Moderately supported

Clinical evidence dominant · Open Targets 0.50

View evidence synthesis (2)

Irritable Bowel SyndromeModerately supported

0.72

agreement 0.56–0.87

Clinical95%Literature5%

Open Targets aggregate 0.58 · 2 independent evidence families

ConstipationModerately supported

0.62

agreement 0.46–0.77

Clinical98%Literature2%

Open Targets aggregate 0.50 · 2 independent evidence families

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations

Irritable Bowel Syndrome0.58

Constipation0.50

Drug development

4 compounds recorded · 2 approved · 2 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 2 drugs that target this protein in Forefront's canonical graph (2 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (4)

PLECANATIDEApproval

DOLCANATIDEPhase 2

LINACLOTIDEApproval

INDUSATUMAB VEDOTINPhase 2

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small molecules — Emerging

Feasibility evidence (structure with ligand and druggable family) — no clinical-stage drug of this modality recorded.

Antibodies — Emerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (database ubiquitination) — no clinical-stage drug of this modality recorded.

Other modalities — Strong

Approved Drug support this modality.

View underlying tractability evidence (7)

SM · Structure with LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Database UbiquitinationOC · Approved Drug

Raw Open Targets tractability assessment buckets, by modality.

Clinical trials

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

Phase II Randomized, Placebo-Controlled Trial of Linaclotide to Demonstrate Bioactivity in Patients With Sporadic Colorectal Adenomas and With Colorectal CancerPHASE2

ACTIVE_NOT_RECRUITING · via linaclotide · NCT03796884

A Multi-center, Randomized, Double-blind, Placebo-controlled Phase III Clinical Study to Evaluate the Efficacy and Safety of Plecanatide in the Treatment of Functional Constipation in Chinese Patients for up to 12 WeeksPHASE3

COMPLETED · via plecanatide · NCT05151328

Efficacy and Safety of Linaclotide in Patients With Overlap of Functional Dyspepsia and Constipation-predominant Irritable Bowel SyndromePHASE4

UNKNOWN · via linaclotide · NCT05134584

A Phase 4, Single-centre, Randomised, Double-blind, Placebo-controlled, Parallel-group, Fixed-dose Study of the Effect of Linaclotide on Abdominal Girth in Participants With Irritable Bowel Syndrome With ConstipationPHASE4

TERMINATED · via linaclotide · NCT02837783

View all trials (26)

An Open-label, Long-term Study to Assess the Immunogenicity of Linaclotide Administered Orally to Adult Patients With Irritable Bowel Syndrome With Constipation or Chronic Idiopathic Constipation.PHASE4

COMPLETED · via linaclotide · NCT02590432

Single-dose Linaclotide for Capsule Endoscopy PreparationPHASE4

COMPLETED · via linaclotide · NCT02465385

A Phase 3, Multicenter, Randomized, Double-blind, Parallel-group, Safety and Efficacy Study of Linaclotide Versus Placebo in Pediatric Subjects, Ages 2 to 5 Years, With Functional Constipation (FC) With a 24-week Open-label Treatment ExtensionPHASE3

COMPLETED · via linaclotide · NCT05652205

A Randomized, Double-blinded, Placebo-controlled, Multicenter Study to Evaluate the Clinical Equivalence of Two Linaclotide Products and the Efficacy and Safety of the Test Formulation of Linaclotide in the Treatment of Chronic Idiopathic ConstipationPHASE3

UNKNOWN · via linaclotide · NCT04804267

A Phase 3, Multicenter, Randomized, Double-blind, Parallel-group, Safety and Efficacy Study of Linaclotide in Pediatric Participants, Ages 6 to 17 Years, With Irritable Bowel Syndrome With Constipation (IBS-C) and of Linaclotide Versus Placebo in Pediatric Participants With Functional Constipation (FC)PHASE3

COMPLETED · via linaclotide · NCT04026113

A Phase 3b, Randomized, Double-blind, Placebo-controlled, Parallel-group Trial of Linaclotide 290 μg Administered Orally for 12 Weeks Followed by a 4-week Randomized Withdrawal Period in Patients With Irritable Bowel Syndrome With ConstipationPHASE3

COMPLETED · via linaclotide · NCT03573908

Phase 3 Study of ASP0456 - A Double-blind, Placebo-controlled, Parallel-group, Comparative Study and an Open-label, Uncontrolled, Long-term Dosing Study in Patients With Chronic Constipation (Not Including Constipation Due to Organic Diseases) -PHASE3

COMPLETED · via linaclotide · NCT02809105

An Open Label, Long Term Safety and Tolerability Study of Plecanatide in Patients With Irritable Bowel Syndrome With Constipation (IBS-C)PHASE3

COMPLETED · via plecanatide · NCT02706483

Second Phase 3 Randomized, 12-Week, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Plecanatide in Patients With Irritable Bowel Syndrome With Constipation (IBS-C)PHASE3

COMPLETED · via plecanatide · NCT02493452

A Randomized, 12-Week, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Plecanatide in Patients With Irritable Bowel Syndrome With Constipation (IBS-C)PHASE3

COMPLETED · via plecanatide · NCT02387359

Phase III Study of ASP0456 - A Double-blind, Placebo-controlled, Parallel-group, Comparative Study and Long-term Study in Patients With Irritable Bowel Syndrome With Constipation (IBS-C)PHASE3

COMPLETED · via linaclotide · NCT02316899

A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group Trial of Linaclotide (72 ug or 145 ug) Administered Orally for 12 Weeks to Patients With Chronic Idiopathic ConstipationPHASE3

COMPLETED · via linaclotide · NCT02291679

A National, Randomized, 12-Week, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of Plecanatide (3.0 and 6.0 mg) in Patients With Chronic Idiopathic ConstipationPHASE3

COMPLETED · via plecanatide · NCT02122471

A Randomized, 12-Week, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of Plecanatide (3.0 and 6.0 mg) in Patients With Chronic Idiopathic Constipation (The CIC3 Study)PHASE3

COMPLETED · via plecanatide · NCT01982240

An Open-Label Extension (OLE), Long-term Safety and Tolerability Study of Plecanatide in Patients With Chronic Idiopathic Constipation (CIC)PHASE3

COMPLETED · via plecanatide · NCT01919697

A Phase 3, International, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Efficacy and Safety Trial of Linaclotide Administered Orally for 12 Weeks to Patients With Irritable Bowel Syndrome With Constipation (IBS-C)PHASE3

COMPLETED · via linaclotide · NCT01880424

Study SP304-20210: A Randomized, 12-Week, Double-Blind, Placebo-Controlled, Repeat-Dose, Oral, Dose-Ranging Study to Assess the Safety and Efficacy of Plecanatide in Patients With Chronic Idiopathic ConstipationPHASE2/PHASE3

COMPLETED · via plecanatide · NCT01429987

An Open-Label, Long-Term Safety Study of Oral Linaclotide Administered to Patients With Chronic Constipation or Irritable Bowel Syndrome With ConstipationPHASE3

COMPLETED · via linaclotide · NCT00765999

An Open-label, Long-term Safety Study of Oral Linaclotide Administered to Patients With Chronic Constipation or Irritable Bowel Syndrome With ConstipationPHASE3

COMPLETED · via linaclotide · NCT00730171

A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group Trial of Linaclotide Administered Orally for 12 Weeks Followed by a 4-Week Randomized Withdrawal Period in Patients With Chronic ConstipationPHASE3

COMPLETED · via linaclotide · NCT00730015

A Phase 2 Dose Finding Study Evaluating the Safety and Efficacy of Linaclotide in Pediatric Subjects 6 Months to Less Than 2 Years of Age With Functional Constipation (FC).PHASE2

COMPLETED · via linaclotide · NCT05760313

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Sequential, Ascending, Multidose Study to Evaluate the Safety and Efficacy of Linaclotide in Pediatric Participants (Age 2 to 5 Years) With Functional ConstipationPHASE2

COMPLETED · via linaclotide · NCT04110145

A Randomized, Double-blind, Placebo-Controlled, Dose Ranging, Parallel-Group Study of the Efficacy and Safety of Plecanatide in Children 6 to <18 Years of Age With Irritable Bowel Syndrome With Constipation (IBS-C)PHASE2

COMPLETED · via plecanatide · NCT03596905

A Randomized, Double-blind, Placebo-controlled, 3 Dose Level, Parallel Group Study of the Efficacy and Safety of Plecanatide in Adolescents 12 to < 18 Years of Age With Chronic Idiopathic Constipation (CIC)PHASE2

COMPLETED · via plecanatide · NCT03120520

A Phase 2b, Randomized, Double-blind, Double-dummy, Placebo-controlled, Parallel-group, Dose-range-finding Study of Two Delayed Release Formulations of Linaclotide Administered Orally for 12 Weeks to Patients With Irritable Bowel Syndrome With ConstipationPHASE2

COMPLETED · via linaclotide · NCT02559206

A Randomized, 12-Week, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Assess the Safety and Efficacy of Plecanatide in Patients With Irritable Bowel Syndrome With Constipation (IBS-C)PHASE2

COMPLETED · via plecanatide · NCT01722318

ClinicalTrials.gov via the drug-target graph.

What's happening now

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for a drug that targets this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

Regulatory approval2012-11-26
Approval: Constella (EMA)
ema · regulatory · ema · via linaclotide

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.