Protein / target

Progesterone receptor

PGRP06401Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
23
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Estrogen response element binding

Primary system

Endocrine & metabolic

Strongest disease association

endometriosis

Genetic evidence · score 0.48

Therapeutic maturity

Clinically validated target

23 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

23 approved · 7 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

The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Depending on the isoform, progesterone receptor functions as a transcriptional activator or repressor

Subcellular location

NucleusCytoplasmMitochondrion outer membrane
Domains and Gene Ontology detail (33)

Domains & features

NR LBD

Gene Ontology

  • Cchromatin
  • Ccytosol
  • Cmitochondrial outer membrane
  • Cnucleoplasm
  • Cnucleus
  • Cplasma membrane
  • FATPase binding
  • FDNA binding
  • FDNA-binding transcription activator activity, RNA polymerase II-specific
  • FDNA-binding transcription factor activity, RNA polymerase II-specific
  • Fenzyme binding
  • Festrogen response element binding

933 aa · 99 kDa · 5 isoforms

Biological roles

Reactome v97

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

Transcriptional regulationUniProt · GO · ReactomeNuclear receptor signallingGO · ReactomeKinase signallingGOImmune signallingUniProt
View supporting evidence

Transcriptional regulation

  • ·The steroid hormones and their receptors are involved in the regulation of eukaryotic ge…
  • ·DNA-binding transcription activator activity, RNA polymerase II-specific
  • ·DNA-binding transcription factor activity, RNA polymerase II-specific
  • ·RNA polymerase II cis-regulatory region sequence-specific DNA binding

Nuclear receptor signalling

  • ·DNA-binding transcription factor activity, RNA polymerase II-specific
  • ·nuclear receptor activity
  • ·nuclear receptor-mediated steroid hormone signaling pathway
  • ·HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand

Kinase signalling

  • ·negative regulation of phosphorylation

Immune signalling

  • ·The steroid hormones and their receptors are involved in the regulation of eukaryotic ge…
View underlying pathways (7)

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.

NCOA1NCOR1NCOR2HSP90A…NCOA3ERBB2HSP90A…FKBP4FKBP5ESR1PGR

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.

Progesterone
Narrow target profileApprovedAgonist

Progesterone receptor agonist

Appears in clinical studies involving amenorrhea, atypical endometrial hyperplasia, hemorrhage, Infertility

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

Cyproterone Acetate
Narrow target profilePhase 3Agonist

Progesterone receptor agonist

Appears in clinical studies involving prostate cancer, Hot flashes, prostate adenocarcinoma, endometriosis

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

Medroxyprogesterone Acetate
Narrow target profileApprovedAgonist

Progesterone receptor agonist

Appears in clinical studies involving renal carcinoma, endometriosis, hemorrhage, hyperplasia

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

Mifepristone
Narrow target profileApprovedAntagonist

Progesterone receptor antagonist

Appears in clinical studies involving Cushing syndrome, psychotic disorder, major depressive disorder, Uterine leiomyoma

Direct interaction with this protein · 1 of 2 recorded protein targets — narrow recorded profile

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.

Strongest genetic associations

Human genetic evidence — the most direct causal link between this target and a disease.

endometriosis0.48

Genetic · overall 0.67

Highest-confidence therapeutic associations

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

contraception0.98

Clinical · overall 0.60

acne0.98

Clinical · overall 0.60

Infertility0.97

Clinical · overall 0.60

Dysmenorrhea0.95

Clinical · overall 0.58

hemorrhage0.94

Clinical · overall 0.58

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

breast cancer0.58

Literature

Uterine leiomyoma0.57

Clinical

Menorrhagia0.57

Clinical

Anorexia0.56

Clinical

Show all associations
endometriosis0.67
Infertility0.60
contraception0.60
acne0.60
Dysmenorrhea0.58
breast cancer0.58
hemorrhage0.58
Uterine leiomyoma0.57
Menorrhagia0.57
Anorexia0.56

Open Targets ranks 2,083 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 · 31 total

MIFEPRISTONEApproval

Cushing syndrome · psychotic disorder · major depressive disorder

ULIPRISTAL ACETATEApproval

contraception · Uterine leiomyoma · uterine corpus leiomyoma

TRIMEGESTONEApproval

contraception · ovulation

LEVONORGESTRELApproval

Menorrhagia · osteoporosis · contraception

NORGESTIMATEApproval

acne · contraception · anorexia nervosa

NORGESTRELApproval

Menorrhagia · hemorrhage · contraception

NORETHINDRONEApproval

endometriosis · Dysmenorrhea · Ovarian Hyperandrogenism

CYPROTERONE ACETATEPhase 3

prostate cancer · Hot flashes · prostate adenocarcinoma

HYDROXYPROGESTERONE CAPROATEApproval

premature birth · preeclampsia · placenta praevia

NORELGESTROMINApproval

contraception · pregnancy

Tractability

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyAB · GO CC high confPR · UniProt UbiquitinationPR · Database UbiquitinationPR · Small Molecule Binder

Safety liabilities

Contraceptivereceptor bindingregulation of steroid hormone biosynthetic processEmergency contraceptivesinduction of medical abortionregulation of transcription factor activityregulation of steroid biosynthetic process

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)

UNKNOWN · via Cyproterone Acetate · NCT00363285

TERMINATED · via Mifepristone · NCT04588688

TERMINATED · via Progesterone · NCT00946088

COMPLETED · via Medroxyprogesterone Acetate · NCT00191113

TERMINATED · via Mifepristone · NCT00867360

ClinicalTrials.gov via the drug-target graph.

Related literature

20

Papers indexed under “Receptors, Progesterone” — a subject heading that covers this protein without being specific to it. Shown as context; not counted as this protein's own research activity.

Biomarkers in breast cancer 2024: an updated consensus statement by the Spanish Society of Medical Oncology and the Spanish Society of Pathology.

Colomer R · Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024

Datopotamab Deruxtecan in Advanced or Metastatic HR+/HER2- and Triple-Negative Breast Cancer: Results From the Phase I TROPION-PanTumor01 Study.

Bardia A · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024

Hormone Receptor Signaling and Breast Cancer Resistance to Anti-Tumor Immunity.

Moisand A · International journal of molecular sciences · 2023

Europe PMC literature, reached through a MeSH descriptor linked to this protein.

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.

endometriosisWell supported
0.87
agreement 0.760.98
Clinical56%Genetic37%Literature7%

Open Targets aggregate 0.67 · 3 independent evidence families

Uterine leiomyomaWell supported
0.77
agreement 0.640.89
Clinical71%Animal model23%Literature6%

Open Targets aggregate 0.57 · 3 independent evidence families

InfertilityModerately supported
0.74
agreement 0.580.89
Clinical94%Literature6%

Open Targets aggregate 0.60 · 2 independent evidence families

contraceptionModerately supported
0.74
agreement 0.570.90
Clinical100%

Open Targets aggregate 0.60 · 1 independent evidence family

acneModerately supported
0.74
agreement 0.580.89
Clinical100%Literature0%

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

34

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. Regulatory action2026-07-21
    Biotech industry leaders file brief backing FDA against ‘malicious’ mifepristone challenge

    Fierce Biotech · news · via Mifepristone

  2. Supplemental approval2026-07-16

    Supplemental approval: PROGESTERONE (NDA022057)

    fda · regulatory · fda · via Progesterone

  3. Label change2026-07-15

    Label change: PROGESTERONE (NDA022057)

    fda · regulatory · fda · via Progesterone

  4. New publication2024-11-29
    Metabolic control of luteinizing hormone-responsive ovarian steroidogenesis.

    The Journal of biological chemistry · 2025 · 7 citations · Europe PMC · via Progesterone

  5. New publication2024-08-01
    Sex hormones differently regulate lipid metabolism genes in primary human hepatocytes.

    BMC endocrine disorders · 2024 · 8 citations · Europe PMC · via Progesterone

  6. Product recall2024-07-26

    Recall (Class II): PROGESTERONE

    fda · safety · fda · via Progesterone

  7. New publication2024-04-23
    Diagnostic and therapeutic use of oral micronized progesterone in endocrinology.

    Reviews in endocrine & metabolic disorders · 2024 · 15 citations · Europe PMC · via Progesterone

  8. New publication2024-03-15
    Disturbed sex hormone milieu in males and females with major depressive disorder and low-grade inflammation.

    Journal of affective disorders · 2024 · 14 citations · Europe PMC · via Progesterone

  9. New publication2023-11-07
    The role of maternal hormones in regulating autonomic functions during pregnancy.

    Journal of neuroendocrinology · 2023 · 9 citations · Europe PMC · via Progesterone

  10. New publication2023-10-28
    Mammary Microvessels are Sensitive to Menstrual Cycle Sex Hormones.

    Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023 · 9 citations · Europe PMC · via Progesterone

  11. New publication2023-10-12
    Menstrual cycle hormones and oral contraceptives: a multimethod systems physiology-based review of their impact on key aspects of female physiology.

    Journal of applied physiology (Bethesda, Md. : 1985) · 2023 · 75 citations · Europe PMC · via Progesterone

  12. New publication2023-09-01
    Anorexia nervosa and adrenal hormones: a systematic review and meta-analysis.

    European journal of endocrinology · 2023 · 9 citations · Europe PMC · via Progesterone

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.