Protein / target

5-hydroxytryptamine receptor 2C

HTR2CP28335Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
37
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding

Primary system

Nervous system

Strongest disease association

autism

Clinical evidence · score 0.61

Therapeutic maturity

Clinically validated target

37 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

37 approved · 4 in clinical development

30 linked trials

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

G protein-coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:12970106, PubMed:18703043, PubMed:19057895, PubMed:29398112, PubMed:7895773). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-iodophenyl-2-aminopropane (DOI) and lysergic acid diethylamide (LSD) (PubMed:19057895, PubMed:29398112). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors (PubMed:18703043, PubMed:29398112). HTR2C is coupled to G(q)/G(11) G alpha proteins and activates phospholipase C-beta, releasing diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) second messengers that modulate the activity of phosphatidylinositol 3-kinase and promote the release of Ca(2+) ions from intracellular stores, respectively (PubMed:18703043, PubMed:29398112). Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways (PubMed:29398112). Regulates neuronal activity via the activation of short transient receptor potential calcium channels in the brain, and thereby modulates the activation of pro-opiomelanocortin neurons and the release of CRH that then regulates the release of corticosterone (By similarity). Plays a role in the regulation of appetite and eating behavior, responses to anxiogenic stimuli and stress (By similarity). Plays a role in insulin sensitivity and glucose homeostasis (By similarity)

Subcellular location

Cell membrane
Domains and Gene Ontology detail (27)

Gene Ontology

  • Cdendrite
  • CG protein-coupled serotonin receptor complex
  • Cplasma membrane
  • Csynapse
  • F1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding
  • FG protein-coupled serotonin receptor activity
  • FGq/11-coupled serotonin receptor activity
  • Fidentical protein binding
  • Fneurotransmitter receptor activity
  • Fserotonin binding
  • Fserotonin receptor activity
  • Pbehavioral fear response

458 aa · 52 kDa · 2 isoforms

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

G protein-coupled signallingUniProt · GOSynaptic signallingGOMotor controlGO
View supporting evidence

G protein-coupled signalling

  • ·G protein-coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:12970106, PubMed:…
  • ·G protein-coupled serotonin receptor complex
  • ·G protein-coupled serotonin receptor activity
  • ·G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messen…

Synaptic signalling

  • ·synapse
  • ·neurotransmitter receptor activity
  • ·chemical synaptic transmission

Motor control

  • ·locomotory behavior
View underlying pathways (2)

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

GNAQHTR2AHTR2BGNASGNB1GNG2CACNA1DCACNA1CGNA11SLC6A4HTR2C

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Drugs targeting this protein

4

Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.

Risperidone
Narrow target profileApprovedAntagonist

Serotonin 2c (5-HT2c) receptor antagonist

Appears in clinical studies involving bipolar disorder, schizophrenia, aggressive behavior, autism

Direct interaction with this protein · 1 of 3 recorded protein targets — narrow recorded profile

Quetiapine Fumarate
Narrow target profileApprovedAntagonist

Serotonin 2c (5-HT2c) receptor antagonist

Appears in clinical studies involving schizophrenia, bipolar disorder, bipolar I disorder, major depressive disorder

Direct interaction with this protein · 1 of 3 recorded protein targets — narrow recorded profile

agomelatine
Narrow target profileApprovedAntagonist

Serotonin 2c (5-HT2c) receptor antagonist

Appears in clinical studies involving major depressive disorder, treatment resistant depression, obsessive-compulsive disorder, depressive disorder

Direct interaction with this protein · 1 of 3 recorded protein targets — narrow recorded profile

olanzapine
ApprovedAntagonist

Serotonin 2c (5-HT2c) receptor antagonist

Appears in clinical studies involving bipolar disorder, schizophrenia, major depressive disorder, Agitation

Direct interaction with this protein · 1 of 5 recorded protein targets

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

Translational evidence

Open Targets 26

Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

schizophrenia1.00

Clinical · overall 0.61

bipolar disorder1.00

Clinical · overall 0.61

major depressive disorder1.00

Clinical · overall 0.61

autism1.00

Clinical · overall 0.61

aggressive behavior0.99

Clinical · overall 0.60

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

psychotic disorder0.60

Clinical

bipolar I disorder0.60

Clinical

Agitation0.60

Clinical

depressive disorder0.59

Clinical

Dravet syndrome0.58

Clinical

Show all associations
autism0.61
schizophrenia0.61
bipolar disorder0.61
major depressive disorder0.61
psychotic disorder0.60
bipolar I disorder0.60
aggressive behavior0.60
Agitation0.60
depressive disorder0.59
Dravet syndrome0.58

Open Targets ranks 648 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.

Known drugs · 44 total

FENFLURAMINE HYDROCHLORIDEApproval

Seizure · Dravet syndrome · encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy

CHLORPROTHIXENEApproval

psychotic disorder · psychotic disorder

LORCASERINApproval

obesity disorder · Obesity · Overweight

DEXFENFLURAMINE HYDROCHLORIDEUnknown
VABICASERINPhase 2

psychotic disorder · schizophrenia

QUETIAPINEApproval

schizophrenia · psychotic disorder · alcohol dependence

TRIMIPRAMINEApproval

major depressive disorder · glioblastoma

CLOTHIAPINEApproval

schizophrenia · psychotic disorder

TEDATIOXETINEPhase 2

major depressive disorder · generalized anxiety disorder

ZIPRASIDONE HYDROCHLORIDEApproval

bipolar disorder · schizophrenia · Agitation

Tractability

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Small Molecule Binder

Safety liabilities

increased convulsionsmetabolic syndromedecreased locomotor activityincreased memoryabnormal mouth movementsantipsychotic-induced weight gainpenile erectiondecreased convulsionsdecreased eatingIncreased, Kidney Failureweight gaindecreased memory

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.

Show remaining trials (24)

COMPLETED · via Risperidone · NCT04587115

COMPLETED · via Risperidone · NCT00073658

ClinicalTrials.gov via the drug-target graph.

Forefront confidence

Synthesis

Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.

autismWell supported
0.78
agreement 0.660.90
Clinical85%Animal model13%RNA expression1%Literature1%

Open Targets aggregate 0.61 · 4 independent evidence families

schizophreniaWell supported
0.76
agreement 0.600.91
Clinical96%Literature4%

Open Targets aggregate 0.61 · 2 independent evidence families

bipolar disorderWell supported
0.75
agreement 0.600.91
Clinical97%Literature3%

Open Targets aggregate 0.61 · 2 independent evidence families

major depressive disorderWell supported
0.75
agreement 0.600.91
Clinical97%Literature3%

Open Targets aggregate 0.61 · 2 independent evidence families

psychotic disorderModerately supported
0.74
agreement 0.590.90
Clinical98%Literature2%

Open Targets aggregate 0.60 · 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 underlying per-type scores are shown above so the calculation can be checked.

What's happening now

60

Recent activity around this target, drawn from one canonical event stream. Every item is reached through 4 drugs that target this protein, so each event is news about that drug rather than about the protein directly.

  1. Label change2026-07-01

    Label change: RISPERIDONE (ANDA076996)

    fda · regulatory · fda · via Risperidone

  2. Label change2026-06-08

    Label change: RISPERIDONE (ANDA077494)

    fda · regulatory · fda · via Risperidone

  3. New publication2025-12-22
    STAT3 Signaling Mediates Agomelatine Restoration of Prefrontal Cortex Synaptic Plasticity in Chronic Social Defeat Stress Mice.

    Molecular neurobiology · 2025 · 1 citation · Europe PMC · via agomelatine

  4. Label change2025-11-04

    Label change: RISPERIDONE (ANDA091384)

    fda · regulatory · fda · via Risperidone

  5. Withdrawn from market2025-08-12

    Market withdrawal: Olanzapine Apotex (EMA)

    ema · market · ema · via olanzapine

  6. Label change2025-06-17

    Label change: RISPERIDONE (ANDA079088)

    fda · regulatory · fda · via Risperidone

  7. Label change2025-01-22

    Label change: RISPERIDONE (ANDA076996)

    fda · regulatory · fda · via Risperidone

  8. Label change2025-01-14

    Label change: RISPERIDONE (ANDA076996)

    fda · regulatory · fda · via Risperidone

  9. Label change2024-09-09

    Label change: RISPERIDONE (ANDA091384)

    fda · regulatory · fda · via Risperidone

  10. Label change2024-06-12

    Label change: RISPERIDONE (ANDA079088)

    fda · regulatory · fda · via Risperidone

  11. Label change2024-06-12

    Label change: RISPERIDONE (ANDA079088)

    fda · regulatory · fda · via Risperidone

  12. Label change2024-06-12

    Label change: RISPERIDONE (ANDA079088)

    fda · regulatory · fda · via Risperidone

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.