PGR

Summary

PGR (progesterone receptor, HGNC:8910) is a protein-coding gene on chromosome 11q22.1, encoding Progesterone receptor (P06401). The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. In precision oncology, PGR Expression confers sensitivity to Tamoxifen in Breast Cancer (CIViC Level B); 1 further curated variant–drug associations are listed below.

This gene encodes a member of the steroid receptor superfamily. The encoded protein mediates the physiological effects of progesterone, which plays a central role in reproductive events associated with the establishment and maintenance of pregnancy. This gene uses two distinct promotors and translation start sites in the first exon to produce several transcript variants, both protein coding and non-protein coding. Two of the isoforms (A and B) are identical except for an additional 165 amino acids found in the N-terminus of isoform B and mediate their own response genes and physiologic effects with little overlap.

Source: NCBI Gene 5241 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 143 total
• Phenotypes (HPO): 3
• Druggable target: yes — 264 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 2 curated variant–drug associations
• Transcription factor: yes — 143 downstream targets (CollecTRI)
• MANE Select transcript: NM_000926

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8910
Approved symbol	PGR
Name	progesterone receptor
Location	11q22.1
Locus type	gene with protein product
Status	Approved
Aliases	PR, NR3C3
Ensembl gene	ENSG00000082175
Ensembl biotype	protein_coding
OMIM	607311
Entrez	5241

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron

ENST00000263463, ENST00000325455, ENST00000526300, ENST00000528960, ENST00000530764, ENST00000533207, ENST00000534013, ENST00000534780, ENST00000619228, ENST00000632634

RefSeq mRNA: 4 — MANE Select: NM_000926 NM_000926, NM_001202474, NM_001271161, NM_001271162

CCDS: CCDS59229, CCDS8310

Canonical transcript exons

ENST00000325455 — 8 exons

Exon	Start	End
ENSE00000745002	101091760	101091876
ENSE00000795216	101062447	101062752
ENSE00001350778	101029624	101039271
ENSE00003543275	101051424	101051568
ENSE00003582312	101049929	101050059
ENSE00003586936	101126007	101126158
ENSE00003588918	101041945	101042102
ENSE00003734395	101127434	101129813

Expression profiles

Bgee: expression breadth ubiquitous, 197 present calls, max score 95.94.

FANTOM5 (CAGE): breadth broad, TPM avg 1.8996 / max 442.4391, expressed in 235 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
121938	0.5275	134
121941	0.4457	166
121934	0.2073	98
121940	0.2010	105
121939	0.1701	94
121935	0.1517	90
121937	0.0675	45
121936	0.0287	12
121931	0.0280	11
121927	0.0237	11

Top tissues by expression

278 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
endometrium	UBERON:0001295	95.94	gold quality
germinal epithelium of ovary	UBERON:0001304	94.92	gold quality
endocervix	UBERON:0000458	94.16	gold quality
body of uterus	UBERON:0009853	93.12	gold quality
right uterine tube	UBERON:0001302	92.85	gold quality
uterus	UBERON:0000995	91.75	gold quality
cauda epididymis	UBERON:0004360	90.14	gold quality
myometrium	UBERON:0001296	89.99	gold quality
adult organism	UBERON:0007023	89.52	gold quality
seminal vesicle	UBERON:0000998	88.65	gold quality
ectocervix	UBERON:0012249	87.97	gold quality
heart right ventricle	UBERON:0002080	87.26	gold quality
caput epididymis	UBERON:0004358	86.69	gold quality
mammary duct	UBERON:0001765	85.99	gold quality
left uterine tube	UBERON:0001303	84.69	gold quality
female reproductive system	UBERON:0000474	84.47	gold quality
left ovary	UBERON:0002119	83.35	gold quality
sperm	CL:0000019	83.09	gold quality
smooth muscle tissue	UBERON:0001135	83.09	gold quality
epithelium of mammary gland	UBERON:0003244	82.66	gold quality
vagina	UBERON:0000996	80.38	gold quality
male germ cell	CL:0000015	80.31	gold quality
ovary	UBERON:0000992	80.23	gold quality
mammalian vulva	UBERON:0000997	80.20	gold quality
right ovary	UBERON:0002118	79.96	gold quality
fallopian tube	UBERON:0003889	79.37	gold quality
stromal cell of endometrium	CL:0002255	79.35	gold quality
popliteal artery	UBERON:0002250	79.20	gold quality
tibial artery	UBERON:0007610	79.15	gold quality
uterine cervix	UBERON:0000002	79.04	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-10287	yes	46.74
E-ANND-3	yes	7.30
E-MTAB-8060	no	68.87

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

143 targets.

Target	Regulation
ABCB1	Activation
ABCG2	Unknown
ACP3	Unknown
ACTG2	Activation
ADAM2
ADAMTS1	Unknown
ADCYAP1	Activation
ATP1B1	Unknown
BCL2	Activation
BCL2L1	Repression
CALCA
CAT
CCN1	Unknown
CCND1	Unknown
CCT6A
CD28
CDK2AP1	Unknown
CDKN1A	Unknown
CDKN1B
COL5A2
COMT	Unknown
CRABP2	Unknown
CRH	Repression
CRYGB	Repression
CSN2	Unknown
CTSV	Unknown
CXCL1	Activation
CYP19A1	Repression
CYP1A1	Unknown
DKK1	Unknown

JASPAR motifs

Motif	Name	Family
MA2327.1	PGR	Steroid hormone receptors (NR3)

JASPAR matrix evidence (PMIDs): PMID:25779349

Upstream regulators (CollecTRI, top): AP1, ARNT, CTCFL, EPAS1, ESR1, ESR2, FOS, FOXC1, GATA5, HOXA5, HOXB4, JUN, KAT5, KDM5A, KLF9, NCOR1, NFIL3, NFKB, NONO, NPR1, NR2F2, PGR, RELA, SFPQ, SP1, SP3, TRERF1

miRNA regulators (miRDB)

357 targeting PGR, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-19A-3P	99.98	75.33	2762

Literature-anchored findings (GeneRIF, showing 40)

• isoform-specific genes can be used to screen for ligands that selectively modulate the activity of PR-A or PR-B (PMID:11717311)
• these results show that although estrogen can up-regulate endogenous PR gene expression in osteoblasts via both ER isoforms, ER-alpha is the predominant inducer. (PMID:11918216)
• cloning and genomic organization (PMID:11948021)
• May be an important finding in attempting to characterize both the molecular etiology of implantation and the molecular pathophysiology of spontaneous abortion. (PMID:12009358)
• The polymorphism of the progesterone receptor (PR) is not associated with a reduced or increased risk of breast cancer. However, this study cannot exclude a small reduced or increased risk associated with the T allele, especially the rare TT genotype. (PMID:12010857)
• New human breast cancer cells to study isoform ratio effects and ligand-independent gene regulation. (PMID:12021276)
• consistent occurrence of progesterone-receptor immunoreactivity in meningothelioid nodules detected in surgical specimens of lung carcinomas (PMID:12021930)
• Coactivator/corepressor ratios modulate progesteronse receptor-mediated transcription by RU486 (PMID:12048256)
• Progesterone receptor activates its promoter activity thru an active Sp1 site in human endometrial stromal cells. hPRA capability was stronger than hPRB. The ligand binding domain, but not DNA-binding domain, of hPR was required for transactivation. (PMID:12088866)
• appears to be uniformly expressed in leiomyomatosis peritonealis disseminata (LPD)nodules from premenopausal and postmenopausal women, supporting the contention that hormones influence the development of LPD in all cases, regardless of menopausal status (PMID:12090595)
• decrease in estrogen receptor alpha and progesterone receptor A and B concentration in the early phase of first stage labor may play a role in cervical dilation at term (PMID:12113882)
• conclude that autoinhibition and transrepression involve N-terminal sumoylation combined with intramolecular N/C-terminal communication (PMID:12114521)
• down-regulation of PRA is associated with the development of ovarian epithelial carcinoma (PMID:12149147)
• statistically significant association between the +331G/A polymorphism and the risk of endometrial cancer (PMID:12218173)
• significantly higher percentage of spermatozoa with physiologically active plasma membrane lacked progesterone receptor expression in all categories of men with infertility (PMID:12297552)
• Progesterone receptor mRNA variant containing novel exon insertions between exon 4 and exon 5 in human uterine endometrium. The i45 PR mRNA variant was detected in uterine endometrial cancer and in normal endometrium. (PMID:12402980)
• progesterone may be involved in regulation of the growth and development of neurogenic tumors via progesterone receptor (PMID:12414909)
• studies suggest that the cooperative interaction of the estrogen receptor with Fos and Jun proteins helps confer estrogen responsiveness to the endogenous progesterone receptor gene (PMID:12446585)
• model to study functional differences between progesterone receptors A and B isoforms in human endometrial carcinoma cells revealed distinctive differences in target gene regulation between the two (PMID:12517594)
• Sumoylation was shown to increase progesterone receptor-SRC-1 interaction (PMID:12529333)
• low PR status may serve as an indicator of activated growth factor signaling in breast tumor cells, and therefore of an aggressive tumor phenotype and resistance against hormonal therapy (PMID:12554765)
• a regulatory role for MAPK in nuclear steroid hormone receptor subcellular localization (PMID:12554776)
• small, hormone-receptor-positive breast cancers (with a theoretical good prognosis) may carry an elevated risk of nodal involvement if accumulation of uPA-PAI-1 complexes is shown inside their tumour cells by means of immunohistochemistry. (PMID:12556966)
• Estrogen receptor and progesterone receptor concentrations and ERalpha transcription levels were not statistically different between ethnic backgrounds.A causative role for these receptors in the ethnic variation of leiomyoma seems unlikely (PMID:12594000)
• 2 domains of PRB, ERID-I and -II, mediate a direct interaction with the ligand-binding domain of ERalpha. ERID-I and ERID-II flank a proline cluster responsible for binding of PRB to c-Src. (PMID:12612073)
• Cloning and expression of a new truncated, progesterone receptor. (PMID:12644308)
• analysis of isoforms of progesterone receptor (PMID:12650698)
• PR-A and PR-B have a role in progesterone-dependent gene transcription in the uterus involving select KLF members (PMID:12672823)
• Novel alternatively spliced variant with a deletion of 52 base pairs in exon 6 of the progesterone receptor is associated with breast cancer (PMID:12673676)
• lack of progesterone receptor in breast cancer is associated with aneuploidy and median S-phase fraction (PMID:12699057)
• Data show that differential recruitment of coactivators by progesterone and glucocorticoid receptors determines the assembly of coactivator complexes on target promoters to mediate specific transcription signals. (PMID:12748280)
• Results provided in vitro evidence of the close association of progesterone receptor with differentiation in breast cancer. (PMID:12759236)
• that SMRT and DAX-1 repress agonist-dependent activity of progesterone receptors (PMID:12771131)
• malignant ovarian epithelial cells demonstrated multiple alterations in the expression of estrogen receptor-alpha, estrogen receptor-beta, progesterone receptor A, and progesterone receptor B (PMID:12861133)
• Progesterone receptor promoter methylation may be a molecular marker in various cancer detections. (PMID:12899921)
• Two isoforms of this protein stabilize active receptor conformers within an ensemble distribution of active and inactive conformational states. (PMID:12943706)
• Loss of PR expression in human endometrial cancer may lead to development of a more invasive phenotype of the respective tumor. (PMID:14519645)
• A novel protein-mediated activity in rabbit reticulocyte lysates is required in an additional, heretofore unrecognized, activation step required for PR to become transcriptionally competent on chromatin templates. (PMID:14551264)
• glucocorticoid and mineralocorticoid cross-talk with PR to produce progesterone-like effects in breast cancer cells (PMID:14617569)
• Progesterone receptor transcription and non-transcription signaling mechanisms [review] (PMID:14667966)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pgr	ENSDARG00000035966
mus_musculus	Pgr	ENSMUSG00000031870
rattus_norvegicus	Pgr	ENSRNOG00000006831
drosophila_melanogaster	ERR	FBGN0035849

Paralogs (8): ESR1 (ENSG00000091831), NR3C1 (ENSG00000113580), ESRRB (ENSG00000119715), ESR2 (ENSG00000140009), NR3C2 (ENSG00000151623), AR (ENSG00000169083), ESRRA (ENSG00000173153), ESRRG (ENSG00000196482)

Protein

Protein identifiers

Progesterone receptor — P06401 (reviewed: P06401)

Alternative names: Nuclear receptor subfamily 3 group C member 3

All UniProt accessions (5): P06401, A0A0J9YVP1, Q8NG42, Q8NG44, Q8NG45

UniProt curated annotations — full annotation on 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. Ligand-dependent transdominant repressor of steroid hormone receptor transcriptional activity including repression of its isoform B, MR and ER. Transrepressional activity may involve recruitment of corepressor NCOR2. Transcriptional activator of several progesteron-dependent promoters in a variety of cell types. Involved in activation of SRC-dependent MAPK signaling on hormone stimulation. Increases mitochondrial membrane potential and cellular respiration upon stimulation by progesterone.

Subunit / interactions. Interacts with SMARD1 and UNC45A. Interacts with CUEDC2; the interaction promotes ubiquitination, decreases sumoylation, and represses transcriptional activity. Interacts with PIAS3; the interaction promotes sumoylation of PR in a hormone-dependent manner, inhibits DNA-binding, and alters nuclear export. Interacts with SP1; the interaction requires ligand-induced phosphorylation on Ser-345 by ERK1/2 MAPK. Interacts with PRMT2. Isoform A interacts with NCOR2. Isoform B (but not isoform A) interacts with NCOA2 and NCOA1. Isoform B (but not isoform A) interacts with KLF9. Interacts with GTF2B.

Subcellular location. Nucleus. Cytoplasm Nucleus. Cytoplasm Mitochondrion outer membrane.

Tissue specificity. In reproductive tissues the expression of isoform A and isoform B varies as a consequence of developmental and hormonal status. Isoform A and isoform B are expressed in comparable levels in uterine glandular epithelium during the proliferative phase of the menstrual cycle. Expression of isoform B but not of isoform A persists in the glands during mid-secretory phase. In the stroma, isoform A is the predominant form throughout the cycle. Heterogeneous isoform expression between the glands of the endometrium basalis and functionalis is implying region-specific responses to hormonal stimuli.

Post-translational modifications. Phosphorylated on multiple serine sites. Several of these sites are hormone-dependent. Phosphorylation on Ser-294 occurs preferentially on isoform B, is highly hormone-dependent and modulates ubiquitination and sumoylation on Lys-388. Phosphorylation on Ser-102 and Ser-345 also requires induction by hormone. Basal phosphorylation on Ser-81, Ser-162, Ser-190 and Ser-400 is increased in response to progesterone and can be phosphorylated in vitro by the CDK2-A1 complex. Increased levels of phosphorylation on Ser-400 also in the presence of EGF, heregulin, IGF, PMA and FBS. Phosphorylation at this site by CDK2 is ligand-independent, and increases nuclear translocation and transcriptional activity. Phosphorylation at Ser-162 and Ser-294, but not at Ser-190, is impaired during the G(2)/M phase of the cell cycle. Phosphorylation on Ser-345 by ERK1/2 MAPK is required for interaction with SP1. Sumoylation is hormone-dependent and represses transcriptional activity. Sumoylation on all three sites is enhanced by PIAS3. Desumoylated by SENP1. Sumoylation on Lys-388, the main site of sumoylation, is repressed by ubiquitination on the same site, and modulated by phosphorylation at Ser-294. Ubiquitination is hormone-dependent and represses sumoylation on the same site. Promoted by MAPK-mediated phosphorylation on Ser-294. Ubiquitinated by UBR5, leading to its degradation: UBR5 specifically recognizes and binds ligand-bound PGR when it is not associated with coactivators (NCOAs). In presence of NCOAs, the UBR5-degron is not accessible, preventing its ubiquitination and degradation. Palmitoylated by ZDHHC7 and ZDHHC21. Palmitoylation is required for plasma membrane targeting and for rapid intracellular signaling via ERK and AKT kinases and cAMP generation.

Domain organisation. Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.

Miscellaneous. Produced by alternative promoter usage. Produced by alternative promoter usage. Produced by alternative splicing of isoform B. Produced by alternative promoter usage. Produced by alternative splicing of isoform B.

Similarity. Belongs to the nuclear hormone receptor family. NR3 subfamily.

Isoforms (5)

UniProt ID	Names	Canonical?
P06401-1	B, PRB, PR-B	yes
P06401-2	A, PRA, PR-A
P06401-3	3
P06401-4	4, PR-M
P06401-5	5, delta4

RefSeq proteins (4): NP_000917, NP_001189403, NP_001258090, NP_001258091 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000128	Progest_rcpt	Family
IPR000536	Nucl_hrmn_rcpt_lig-bd	Domain
IPR001628	Znf_hrmn_rcpt	Domain
IPR001723	Nuclear_hrmn_rcpt	Family
IPR013088	Znf_NHR/GATA	Homologous_superfamily
IPR035500	NHR-like_dom_sf	Homologous_superfamily
IPR050200	Nuclear_hormone_rcpt_NR3	Family

Pfam: PF00104, PF00105, PF02161

UniProt features (95 total): mutagenesis site 15, sequence variant 13, helix 13, modified residue 11, region of interest 9, strand 7, compositionally biased region 5, splice variant 5, cross-link 4, short sequence motif 3, zinc finger region 2, sequence conflict 2, turn 2, chain 1, domain 1, DNA-binding region 1, binding site 1

Structure

Experimental structures (PDB)

20 structures.

PDB	Method	Resolution (Å)
1SQN	X-RAY DIFFRACTION	1.45
1SR7	X-RAY DIFFRACTION	1.46
3ZR7	X-RAY DIFFRACTION	1.65
1A28	X-RAY DIFFRACTION	1.8
2W8Y	X-RAY DIFFRACTION	1.8
3ZRB	X-RAY DIFFRACTION	1.8
3G8O	X-RAY DIFFRACTION	1.9
3ZRA	X-RAY DIFFRACTION	1.9
4APU	X-RAY DIFFRACTION	1.9
1ZUC	X-RAY DIFFRACTION	2
2OVH	X-RAY DIFFRACTION	2
3KBA	X-RAY DIFFRACTION	2
4A2J	X-RAY DIFFRACTION	2
3HQ5	X-RAY DIFFRACTION	2.1
3D90	X-RAY DIFFRACTION	2.26
5CC0	X-RAY DIFFRACTION	2.4
4OAR	X-RAY DIFFRACTION	2.41
2C7A	X-RAY DIFFRACTION	2.5
2OVM	X-RAY DIFFRACTION	2.6
1E3K	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P06401-F1	57.66	0.31

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (1): 766

Post-translational modifications (15): 20, 81, 102, 130, 162, 190, 213, 294, 345, 400, 676, 7, 388, 388, 531

Mutagenesis-validated functional residues (15):

Position	Phenotype
7	some loss of sumoylation; when associated with r-531. complete loss of sumoylation; when associated with r-388 and r-531
55	reduces transcriptional activation; when associated with a-58 and a-59.
58	reduces transcriptional activation; when associated with a-55 and a-59.
59	reduces transcriptional activation; when associated with a-55 and a-58.
115	reduces transcriptional activation; when associated with a-118 and a-119.
118	reduces transcriptional activation; when associated with a-115 and a-119.
119	reduces transcriptional activation; when associated with a-115 and a-118.
140	reduces transcriptional activation.
294	no effect on interaction with cuedc2. impaired progesterone-induced transcriptional activity. no cuedc2- nor progestin-m
294	decreases protein stability and increases progesterone-induced transcriptional activity.
344	no interaction with sp1. no change in progestin-induced protein degradation; when associated with a-345. no change in su
345	no change in progestin-induced protein degradation; when associated with a-344. no change in sumoylation; when associate
388	great loss of sumoylation; when associated with r-7. completely abolishes sumoylation; when associated with r-7 and r-53
400	abolishes cdk2-induced activity in the absence, but not in the presence, of progestin. delayed nuclear translocation in
531	some loss of sumoylation; when associated with r-7. completely abolishes sumoylation; when associated with r-7 and r-388

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-1251985	Nuclear signaling by ERBB4
R-HSA-3371497	HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand
R-HSA-383280	Nuclear Receptor transcription pathway
R-HSA-4090294	SUMOylation of intracellular receptors
R-HSA-9018519	Estrogen-dependent gene expression
R-HSA-9927418	Developmental Lineage of Mammary Gland Luminal Epithelial Cells
R-HSA-9927426	Developmental Lineage of Mammary Gland Alveolar Cells

MSigDB gene sets: 287 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_MAMMARY_GLAND_MORPHOGENESIS, BENPORATH_ES_WITH_H3K27ME3, GOBP_GLAND_MORPHOGENESIS, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_EPITHELIAL_CELL_DEVELOPMENT, chr11q22, GOZGIT_ESR1_TARGETS_DN, GOBP_MAMMARY_GLAND_EPITHELIUM_DEVELOPMENT, SCHLESINGER_METHYLATED_DE_NOVO_IN_CANCER, GOBP_CELL_CELL_SIGNALING, GOBP_ANATOMICAL_STRUCTURE_MATURATION

GO Biological Process (19): ovulation from ovarian follicle (GO:0001542), glandular epithelial cell maturation (GO:0002071), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), signal transduction (GO:0007165), cell-cell signaling (GO:0007267), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), nuclear receptor-mediated steroid hormone signaling pathway (GO:0030518), paracrine signaling (GO:0038001), positive regulation of transcription by RNA polymerase II (GO:0045944), lung alveolus development (GO:0048286), regulation of epithelial cell proliferation (GO:0050678), progesterone receptor signaling pathway (GO:0050847), maintenance of protein location in nucleus (GO:0051457), tertiary branching involved in mammary gland duct morphogenesis (GO:0060748), epithelial cell maturation (GO:0002070), mammary gland development (GO:0030879), steroid hormone receptor signaling pathway (GO:0043401)

GO Molecular Function (20): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), transcription coactivator binding (GO:0001223), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), nuclear steroid receptor activity (GO:0003707), nuclear receptor activity (GO:0004879), signaling receptor binding (GO:0005102), steroid binding (GO:0005496), zinc ion binding (GO:0008270), enzyme binding (GO:0019899), estrogen response element binding (GO:0034056), identical protein binding (GO:0042802), ATPase binding (GO:0051117), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515), lipid binding (GO:0008289), sequence-specific DNA binding (GO:0043565), metal ion binding (GO:0046872), sequence-specific double-stranded DNA binding (GO:1990837)

GO Cellular Component (9): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), mitochondrial outer membrane (GO:0005741), cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasm (GO:0005737), mitochondrion (GO:0005739), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Developmental Lineages of the Mammary Gland	2
Signaling by ERBB4	1
Cellular responses to stress	1
Generic Transcription Pathway	1
SUMO E3 ligases SUMOylate target proteins	1
ESR-mediated signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
regulation of gene expression	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
protein binding	3
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
cell communication	2
signaling	2
gene expression	2
regulation of transcription by RNA polymerase II	2
nuclear receptor-mediated steroid hormone signaling pathway	2
DNA-binding transcription factor activity, RNA polymerase II-specific	2
binding	2
intracellular membrane-bounded organelle	2
cytoplasm	2
female gonad development	1
ovulation cycle process	1
ovulation	1
glandular epithelial cell development	1
columnar/cuboidal epithelial cell maturation	1
DNA-templated transcription	1
regulation of RNA biosynthetic process	1
cellular process	1
regulation of cellular process	1
cellular response to stimulus	1
positive regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
steroid hormone receptor signaling pathway	1
nuclear receptor-mediated signaling pathway	1
cell-cell signaling	1
positive regulation of DNA-templated transcription	1
lung development	1
anatomical structure development	1
regulation of cell population proliferation	1
epithelial cell proliferation	1
nucleus	1
protein localization to nucleus	1
maintenance of protein localization in organelle	1
developmental process involved in reproduction	1
mammary gland branching involved in pregnancy	1

Protein interactions and networks

STRING

3834 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PGR	ERBB2	P04626	972
PGR	HSPA4	P34932	959
PGR	HSP90AA1	P07900	956
PGR	HSP90AB1	P08238	950
PGR	PGRMC1	O00264	944
PGR	BRCA1	P38398	929
PGR	NCOA1	Q15788	924
PGR	FKBP5	Q13451	903
PGR	FKBP4	Q02790	885
PGR	CYP19A1	P11511	882
PGR	PGRMC2	O15173	872
PGR	KLF9	Q13886	859
PGR	TP53	P04637	850
PGR	STAT5A	P42229	841
PGR	SRC	P12931	838

IntAct

55 interactions, top by confidence:

A	B	Type	Score
PGR	ESR1	psi-mi:“MI:0915”(physical association)	0.770
ESR1	PGR	psi-mi:“MI:0403”(colocalization)	0.770
ESR1	PGR	psi-mi:“MI:0915”(physical association)	0.770
PGR	CUEDC2	psi-mi:“MI:0915”(physical association)	0.660
CUEDC2	PGR	psi-mi:“MI:0915”(physical association)	0.660
CUEDC2	PGR	psi-mi:“MI:0403”(colocalization)	0.660
PGR	CUEDC2	psi-mi:“MI:0403”(colocalization)	0.660
PGR	PGR	psi-mi:“MI:0407”(direct interaction)	0.620
PGR	STAT3	psi-mi:“MI:0915”(physical association)	0.620
	PGR	psi-mi:“MI:0914”(association)	0.530
PGR		psi-mi:“MI:0914”(association)	0.530

BioGRID (135): PGR (Two-hybrid), SPOP (Affinity Capture-Western), PGR (Affinity Capture-Western), YDJ1 (Reconstituted Complex), DNAJA1 (Reconstituted Complex), HSPA1A (Reconstituted Complex), UBE3A (Two-hybrid), BMI1 (Affinity Capture-Western), PGR (Affinity Capture-Western), BMI1 (Two-hybrid), NCOA1 (Affinity Capture-Western), NCOA2 (Affinity Capture-Western), PGR (Reconstituted Complex), PGR (Reconstituted Complex), KLF9 (Two-hybrid)

ESM2 similar proteins: A1L020, A1L3F4, A7X8B3, A7X8B5, A7X8B7, A7X8B9, A7X8C2, A7X8C4, A7X8C7, A7X8C9, A7X8D2, A7X8D4, A7XW25, O97775, O97776, O97952, O97960, P06401, P10275, P84550, P84551, P89463, Q01JD1, Q05A36, Q0VDT2, Q3UE17, Q5PQQ7, Q5U5Q3, Q69Z36, Q6QT55, Q6ZK57, Q6ZN04, Q71FD5, Q7RTV3, Q7TSJ6, Q7XQN1, Q7XT42, Q84SL2, Q86XN8, Q8BQ89

Diamond homologs: A7X8B3, A7X8B5, A7X8B7, A7X8B9, A7X8C2, A7X8C4, A7X8C7, A7X8C9, A7X8D2, A7X8D4, A7XW16, A7XW20, A7XW25, O08537, O08580, O13012, O13186, O46567, O73673, O95718, O97775, O97776, O97952, O97960, P03372, P04150, P06186, P06211, P06212, P06401, P06536, P06537, P07812, P08235, P10275, P11474, P11475, P15207, P16058, P19091

SIGNOR signaling

19 interactions.

A	Effect	B	Mechanism
NCOR2	down-regulates	PGR	acetylation
PGR	“up-regulates quantity by expression”	KLK4	“transcriptional regulation”
tibolone	“up-regulates activity”	PGR	“chemical activation”
Gbeta	down-regulates	PGR	phosphorylation
ERK1/2	down-regulates	PGR	phosphorylation
GSK3B	“down-regulates quantity by destabilization”	PGR	phosphorylation
NCOA1	up-regulates	PGR
CDK2	down-regulates	PGR	phosphorylation
MAPK1	down-regulates	PGR	phosphorylation
MAPK3	down-regulates	PGR	phosphorylation
ESR1	“down-regulates quantity by repression”	PGR	“transcriptional regulation”
CDK2	unknown	PGR	phosphorylation
PGR	up-regulates	ESR1	binding
CSNK2A1	unknown	PGR	phosphorylation

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

143 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	111
Likely benign	8
Benign	14

Top pathogenic / likely-pathogenic (0)

SpliceAI

1820 predictions. Top by Δscore:

Variant	Effect	Δscore
11:101039118:A:AC	donor_gain	1.0000
11:101039119:C:CC	donor_gain	1.0000
11:101039149:C:A	donor_gain	1.0000
11:101041937:ATACT:A	donor_loss	1.0000
11:101041938:TACTT:T	donor_loss	1.0000
11:101041939:ACTT:A	donor_loss	1.0000
11:101041940:CTTA:C	donor_loss	1.0000
11:101041941:TTA:T	donor_loss	1.0000
11:101041942:TACAT:T	donor_loss	1.0000
11:101041943:A:AC	donor_gain	1.0000
11:101041943:A:C	donor_loss	1.0000
11:101041943:ACAT:A	donor_gain	1.0000
11:101041944:C:CC	donor_gain	1.0000
11:101041944:C:CG	donor_loss	1.0000
11:101041944:CA:C	donor_gain	1.0000
11:101041944:CAT:C	donor_gain	1.0000
11:101041944:CATC:C	donor_gain	1.0000
11:101042103:C:CC	acceptor_gain	1.0000
11:101049953:T:A	donor_gain	1.0000
11:101050075:A:AC	acceptor_gain	1.0000
11:101051420:TTA:T	donor_loss	1.0000
11:101051421:TACT:T	donor_loss	1.0000
11:101051422:A:AC	donor_gain	1.0000
11:101051422:A:C	donor_loss	1.0000
11:101051422:ACT:A	donor_gain	1.0000
11:101051423:C:CA	donor_gain	1.0000
11:101051423:CT:C	donor_gain	1.0000
11:101051423:CTC:C	donor_gain	1.0000
11:101051423:CTCA:C	donor_gain	1.0000
11:101051423:CTCAT:C	donor_gain	1.0000

AlphaMissense

5979 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:101039258:A:G	L887P	1.000
11:101041973:A:G	L873P	1.000
11:101042036:A:G	L852P	1.000
11:101051436:A:G	L782P	1.000
11:101051488:A:G	W765R	1.000
11:101051488:A:T	W765R	1.000
11:101051518:A:G	W755R	1.000
11:101051518:A:T	W755R	1.000
11:101051532:A:G	L750P	1.000
11:101051564:A:C	F739L	1.000
11:101051564:A:T	F739L	1.000
11:101051565:A:G	F739S	1.000
11:101051566:A:G	F739L	1.000
11:101062465:A:G	W732R	1.000
11:101062465:A:T	W732R	1.000
11:101062482:A:G	L726P	1.000
11:101091770:C:A	M632I	1.000
11:101091770:C:G	M632I	1.000
11:101091770:C:T	M632I	1.000
11:101091771:A:C	M632R	1.000
11:101091771:A:G	M632T	1.000
11:101091778:C:G	A630P	1.000
11:101091785:G:C	C627W	1.000
11:101091786:C:G	C627S	1.000
11:101091786:C:T	C627Y	1.000
11:101091787:A:G	C627R	1.000
11:101091787:A:T	C627S	1.000
11:101091795:A:G	L624P	1.000
11:101091799:G:A	R623C	1.000
11:101091799:G:C	R623G	1.000

dbSNP variants (sampled 300 via entrez): RS1000016385 (11:101116537 C>A,G,T), RS1000020897 (11:101054433 A>G), RS1000027191 (11:101073733 G>C,T), RS1000088260 (11:101131315 G>A), RS1000148272 (11:101029952 G>A), RS1000157910 (11:101107380 C>A,T), RS1000188279 (11:101123139 C>T), RS1000199686 (11:101123354 A>G), RS1000217136 (11:101046534 T>C), RS1000241091 (11:101029172 C>G), RS1000270387 (11:101036133 C>T), RS1000291180 (11:101113785 C>A), RS1000362826 (11:101067925 T>TA), RS1000383160 (11:101077694 G>A), RS1000417993 (11:101119949 C>A)

Disease associations

OMIM: gene MIM:607311 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001939	Abnormality of metabolism/homeostasis
HP:0008222	Female infertility

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002541_89	Menarche (age at onset)	7.000000e-14
GCST005929_3	Severity of nausea and vomiting of pregnancy	2.000000e-12
GCST006630_30	Diastolic blood pressure	6.000000e-09
GCST006958_4	Length of menstrual cycle	3.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche
EFO:0009265	nausea and vomiting of pregnancy severity measurement
EFO:0006336	diastolic blood pressure

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL208 (SINGLE PROTEIN), CHEMBL4748219 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

264 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 888,841 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1014	CANDESARTAN CILEXETIL	4	11,194
CHEMBL1023	BEXAROTENE	4	40,951
CHEMBL103	PROGESTERONE	4	162,141
CHEMBL1042	CHOLECALCIFEROL	4	64,162
CHEMBL1059	PREGABALIN	4	26,074
CHEMBL1064	SIMVASTATIN	4	123,163
CHEMBL1065	METHYSERGIDE	4	8,455
CHEMBL1082407	ENZALUTAMIDE	4	9,652
CHEMBL1091	HYDROCORTISONE ACETATE	4	45,061
CHEMBL1095097	EPLERENONE	4	13,067
CHEMBL110691	CHLORMADINONE ACETATE	4	9,747
CHEMBL1112	ARIPIPRAZOLE	4	24,205
CHEMBL1117	IDARUBICIN	4	136,065
CHEMBL1138	EZETIMIBE	4	29,509
CHEMBL1146	CEFAMANDOLE	4	21,886
CHEMBL1152	PREDNISOLONE ACETATE	4	12,111
CHEMBL1159650	CLOBETASOL PROPIONATE	4	30,865
CHEMBL1161	MOMETASONE FUROATE	4	25,884
CHEMBL1162	NORETHINDRONE	4	91,150
CHEMBL1164729	FEBUXOSTAT	4	3,499
CHEMBL1170	TESTOSTERONE PROPIONATE	4
CHEMBL1171837	PONATINIB	4
CHEMBL1173055	RUCAPARIB	4
CHEMBL1194	PRILOCAINE	4
CHEMBL1194666	DIETHYLPROPION	4
CHEMBL1200374	EXEMESTANE	4
CHEMBL1200384	BETAMETHASONE DIPROPIONATE	4
CHEMBL1200386	PREDNICARBATE	4
CHEMBL1200430	ESTRADIOL ACETATE	4
CHEMBL1200438	TIOCONAZOLE	4

Clinical evidence (CIViC)

Drug × variant × indication: 2 predictive associations from 2 curated evidence items; also 2 prognostic.

Variant	Therapy	Indication	Effect	Level	CIViC
PGR Expression	Tamoxifen	Breast Cancer	Sensitivity/Response	CIViC B	EID501
PGR Expression	Exemestane + Tamoxifen	Breast Cancer	Sensitivity/Response	CIViC B	EID502

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

7 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs471767	PGR		0.00	0
rs537681	PGR		0.00	0
rs555653	PGR		0.00	0
rs561610	PGR		0.00	0
rs572943	PGR		0.00	0
rs3740751	PGR		0.00	0
rs11224556	PGR		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: nhr — 3C. 3-Ketosteroid receptors

Most potent curated ligand interactions (15 total), top 15:

Ligand	Action	Affinity	Parameter
medroxyprogesterone	Agonist	9.47	pKi
tanaproget	Agonist	9.3	pIC50
asoprisnil	Antagonist	9.0	pIC50
mifepristone	Mixed	8.96	pKi
norethisterone	Agonist	8.66	pEC50
progesterone	Agonist	8.46	pKi
WAY-255348	Antagonist	8.39	pIC50
onapristone	Antagonist	7.74	pKi
fluticasone propionate	Agonist	7.68	pEC50
budesonide	Agonist	7.15	pEC50
ulipristal acetate	Partial agonist	7.0	pEC50
dydrogesterone	Agonist	6.9	pKi
PF-03882845	Antagonist	6.38	pIC50
APR19	Antagonist	6.24	pIC50
AZD9567	Agonist	5.28	pIC50

Binding affinities (BindingDB)

144 measured of 163 human assays (166 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(1S)-1-[(4aR,5S)-1-(4-fluorophenyl)-4a-methyl-1H,4H,4aH,5H,6H,7H,8H-cyclohexa[f]indazol-5-yl]pent-4-en-1-ol	IC50	1.1 nM
1-ethyl-9-(trifluoromethyl)-1H,2H,3H,6H,7H-quinolino[7,6-b][1,4]oxazin-7-one	KI	1.2 nM
1-(cyclopropylmethyl)-9-(trifluoromethyl)-1H,2H,3H,6H,7H-quinolino[7,6-b][1,4]oxazin-7-one	EC50	1.4 nM
2-{2-bromo-5-[4-({(2,4-difluorophenyl)methylamino}methyl)phenoxy]phenoxy}acetic acid	IC50	1.8 nM
(R)-(4aR,5S)-1-(4-fluorophenyl)-4a-methyl-1H,4H,4aH,5H,6H,7H,8H-cyclohexa[f]indazol-5-ylmethanol	IC50	1.9 nM
(1S)-1-[(4aR,5S)-1-(4-fluorophenyl)-4a-methyl-1H,4H,4aH,5H,6H,7H,8H-cyclohexa[f]indazol-5-yl]-1-(4-fluorophenyl)ethan-1-ol	EC50	2.2 nM
1-(cyclopropylmethyl)-2-ethyl-9-(trifluoromethyl)-1H,2H,3H,6H,7H-quinolino[7,6-b][1,4]oxazin-7-one	EC50	2.3 nM
2-methyl-1-(2,2,2-trifluoroethyl)-9-(trifluoromethyl)-1H,2H,3H,6H,7H-quinolino[7,6-b][1,4]oxazin-7-one	EC50	2.7 nM
(R)-(4aR,5S)-1-(4-fluorophenyl)-4a-methyl-1H,4H,4aH,5H,6H,7H,8H-cyclohexa[f]indazol-5-ylmethanol	EC50	2.9 nM
1-(2,2,2-trifluoroethyl)-9-(trifluoromethyl)-1H,2H,3H,6H,7H-quinolino[7,6-b][1,4]oxazin-7-one	EC50	3.5 nM
2-{5-[4-({(2,4-difluorophenyl)methylamino}methyl)phenoxy]-2-fluorophenoxy}acetic acid	IC50	4.8 nM
BMCL173354 benzo[f]indazole, 6	IC50	5.3 nM
(5S,7’S)-7’-methylspiro[oxolane-5,6’-pentacyclo[8.8.0.02,7.03,5.011,16]octadec-15-ene]-2,14’-dione	IC50	6 nM	US-8987239: 19-nor-steroid derivatives with a 15α,16α-methylene group and a saturated 17,17-spirolactone ring, use thereof, and medicaments containing said derivatives
2-ethyl-1-(2,2,2-trifluoroethyl)-9-(trifluoromethyl)-1H,2H,3H,6H,7H-quinolino[7,6-b][1,4]oxazin-7-one	EC50	6 nM
Mifeprex	IC50	8.8 nM
3-methyl-1-(2,2,2-trifluoroethyl)-9-(trifluoromethyl)-1H,2H,3H,6H,7H-quinolino[7,6-b][1,4]oxazin-7-one	EC50	8.9 nM
BMCL173354 benzo[f]indazole, 7	IC50	10.4 nM
US9034856, 6	IC50	11 nM	US-9034856: 17-(1′propenyl)-17-3′-oxidoestra-4-en-3-one derivative, use thereof, and medicament containing said derivative
4-chloro-1-[(2R,3S)-4,4,4-trifluoro-3-hydroxy-3-methylbutan-2-yl]indole-5-carbonitrile	IC50	15.8 nM	US-10196353: Chemical compounds
RU486	IC50	22 nM
US8987239, 8	IC50	26 nM	US-8987239: 19-nor-steroid derivatives with a 15α,16α-methylene group and a saturated 17,17-spirolactone ring, use thereof, and medicaments containing said derivatives
(8R,9S,10R,13S,14S,17R)-13-methylspiro[1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthrene-17,5’-2H-furan]-3-one	IC50	26 nM	US-9034856: 17-(1′propenyl)-17-3′-oxidoestra-4-en-3-one derivative, use thereof, and medicament containing said derivative
Drospirenone	IC50	27 nM	US-9034856: 17-(1′propenyl)-17-3′-oxidoestra-4-en-3-one derivative, use thereof, and medicament containing said derivative
(8R,9S,10R,13S,14S,17R)-13-ethylspiro[1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthrene-17,5’-furan]-2’,3-dione	IC50	28 nM	US-8937058: 17-hydroxy-19-nor-21-carboxylic acid-steroid γ-lactone derivative, use thereof, and medicament containing the derivative
4-chloro-1-[(2S)-3-hydroxy-3-methylbutan-2-yl]indole-5-carbonitrile	IC50	31.6 nM	US-10196353: Chemical compounds
6-(5-fluoro-2-methoxyphenyl)-2,2-dimethyl-4-[1-(prop-2-en-1-yloxy)ethyl]-1,2-dihydroquinoline	IC50	34 nM
CHEMBL3397788	IC50	36 nM
US8937058, 18	IC50	37 nM	US-8937058: 17-hydroxy-19-nor-21-carboxylic acid-steroid γ-lactone derivative, use thereof, and medicament containing the derivative
CHEMBL3397782	IC50	40 nM
US8937058, 16	IC50	42 nM	US-8937058: 17-hydroxy-19-nor-21-carboxylic acid-steroid γ-lactone derivative, use thereof, and medicament containing the derivative
(7R,8R,9S,10R,13S,14S,17R)-13-ethyl-7-methylspiro[1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthrene-17,5’-furan]-2’,3-dione	IC50	43 nM	US-8937058: 17-hydroxy-19-nor-21-carboxylic acid-steroid γ-lactone derivative, use thereof, and medicament containing the derivative
(7S,8R,9S,10R,13S,14S,17R)-7-ethenyl-13-ethylspiro[1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthrene-17,5’-furan]-2’,3-dione	IC50	50 nM	US-8937058: 17-hydroxy-19-nor-21-carboxylic acid-steroid γ-lactone derivative, use thereof, and medicament containing the derivative
CHEMBL3397781	IC50	53 nM
CHEMBL3397778	IC50	53 nM
(5S,7’S)-18’-ethenyl-7’-methylspiro[oxolane-5,6’-pentacyclo[8.8.0.02,7.03,5.011,16]octadec-15-ene]-2,14’-dione	IC50	55 nM	US-8987239: 19-nor-steroid derivatives with a 15α,16α-methylene group and a saturated 17,17-spirolactone ring, use thereof, and medicaments containing said derivatives
3-methoxy-N-(4-morpholin-4-ylphenyl)naphthalene-2-carboxamide	KD	55 nM	US-20250388575: HETEROBIFUNCTIONAL COMPOUNDS AND METHODS OF TREATING DISEASE
methyl (3aS,4S,9aS,9bR)-2-ethyl-4-(4-ethylsulfanyl-3-methoxyphenyl)-1,3-dioxo-4,6,7,8,9,9b-hexahydro-3aH-pyrrolo[3,4-a]indolizine-9a-carboxylate	KD	55 nM	US-20250388575: HETEROBIFUNCTIONAL COMPOUNDS AND METHODS OF TREATING DISEASE
3-(2-hydroxypropan-2-yl)-7-(2-thiophen-3-ylethynyl)isochromen-1-one	KD	55 nM	US-20250388575: HETEROBIFUNCTIONAL COMPOUNDS AND METHODS OF TREATING DISEASE
2-[2-(3,5-dimethoxyphenyl)ethynyl]-10-prop-2-enylacridin-9-one	KD	55 nM	US-20250388575: HETEROBIFUNCTIONAL COMPOUNDS AND METHODS OF TREATING DISEASE
methyl (1R,5S)-8-[2-(2-chlorophenoxy)ethylcarbamoyl]-3-(2-phenylmethoxyphenyl)-8-azabicyclo[3.2.1]oct-2-ene-2-carboxylate	KD	55 nM	US-20250388575: HETEROBIFUNCTIONAL COMPOUNDS AND METHODS OF TREATING DISEASE
butyl N-[4-[3-[4-(6-methyl-2-pyridinyl)piperazine-1-carbonyl]piperidin-1-yl]piperidine-1-carbonyl]carbamate	IC50	55 nM	US-20250388575: HETEROBIFUNCTIONAL COMPOUNDS AND METHODS OF TREATING DISEASE
butyl N-[4-[3-[4-(2-methylphenyl)piperazine-1-carbonyl]piperidin-1-yl]piperidine-1-carbonyl]carbamate	IC50	55 nM	US-20250388575: HETEROBIFUNCTIONAL COMPOUNDS AND METHODS OF TREATING DISEASE
butyl N-[4-[3-[4-(2-chlorophenyl)piperazine-1-carbonyl]piperidin-1-yl]piperidine-1-carbonyl]carbamate	IC50	55 nM	US-20250388575: HETEROBIFUNCTIONAL COMPOUNDS AND METHODS OF TREATING DISEASE
butyl N-[4-[3-(4-pyridin-2-ylpiperazine-1-carbonyl)piperidin-1-yl]piperidine-1-carbonyl]carbamate	IC50	55 nM	US-20250388575: HETEROBIFUNCTIONAL COMPOUNDS AND METHODS OF TREATING DISEASE
N-[(3-methylphenyl)methyl]-4-[3-(4-pyridin-2-ylpiperazine-1-carbonyl)piperidin-1-yl]piperidine-1-carboxamide	IC50	55 nM	US-20250388575: HETEROBIFUNCTIONAL COMPOUNDS AND METHODS OF TREATING DISEASE
CHEMBL3397780	IC50	58 nM
(5S,7’S)-7’,18’-dimethylspiro[oxolane-5,6’-pentacyclo[8.8.0.02,7.03,5.011,16]octadec-15-ene]-2,14’-dione	IC50	61 nM	US-8987239: 19-nor-steroid derivatives with a 15α,16α-methylene group and a saturated 17,17-spirolactone ring, use thereof, and medicaments containing said derivatives
(5S,7’S)-18’-ethyl-7’-methylspiro[oxolane-5,6’-pentacyclo[8.8.0.02,7.03,5.011,16]octadec-15-ene]-2,14’-dione	IC50	74 nM	US-8987239: 19-nor-steroid derivatives with a 15α,16α-methylene group and a saturated 17,17-spirolactone ring, use thereof, and medicaments containing said derivatives
CHEMBL3397790	IC50	74 nM
(7R,8R,9S,10R,13S,14S,17R)-7,13-diethylspiro[1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthrene-17,5’-furan]-2’,3-dione	IC50	76 nM	US-8937058: 17-hydroxy-19-nor-21-carboxylic acid-steroid γ-lactone derivative, use thereof, and medicament containing the derivative

ChEMBL bioactivities

3192 potent at pChembl≥5 of 3316 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.70	EC50	0.02	nM	CHEMBL556891
10.70	EC50	0.02	nM	CHEMBL557293
10.68	IC50	0.021	nM	MIFEPRISTONE
10.60	IC50	0.025	nM	MIFEPRISTONE
10.60	IC50	0.025	nM	CHEMBL490088
10.55	IC50	0.028	nM	MIFEPRISTONE
10.40	EC50	0.04	nM	CHEMBL556892
10.35	IC50	0.045	nM	MIFEPRISTONE
10.30	EC50	0.05	nM	CHEMBL562509
10.30	IC50	0.05	nM	MIFEPRISTONE
10.27	IC50	0.054	nM	MIFEPRISTONE
10.22	IC50	0.06	nM	CHEMBL455411
10.15	IC50	0.071	nM	CHEMBL455411
10.14	IC50	0.073	nM	MIFEPRISTONE
10.14	IC50	0.073	nM	DESMETHYLMIFEPRISTONE
10.14	IC50	0.073	nM	CHEMBL507253
10.10	Kd	0.08	nM	MOMETASONE FUROATE
10.02	IC50	0.095	nM	CHEMBL221686
10.00	IC50	0.1	nM	MIFEPRISTONE
10.00	EC50	0.1	nM	CHEMBL239957
10.00	EC50	0.1	nM	MEDROXYPROGESTERONE ACETATE
10.00	EC50	0.1	nM	CHEMBL592510
10.00	EC50	0.1	nM	PROGESTERONE
10.00	Ki	0.1	nM	CHEMBL416411
9.98	IC50	0.105	nM	CHEMBL489300
9.92	EC50	0.12	nM	CHEMBL260869
9.92	IC50	0.12	nM	CHEMBL489300
9.92	EC50	0.12	nM	MEDROXYPROGESTERONE ACETATE
9.89	IC50	0.13	nM	MIFEPRISTONE
9.89	IC50	0.13	nM	CHEMBL410304
9.82	EC50	0.15	nM	MEDROXYPROGESTERONE ACETATE
9.82	EC50	0.15	nM	TANAPROGET
9.82	EC50	0.15	nM	CHEMBL260330
9.82	IC50	0.15	nM	CHEMBL453381
9.82	EC50	0.15	nM	CHEMBL292284
9.80	IC50	0.16	nM	CHEMBL455175
9.80	IC50	0.16	nM	CHEMBL507916
9.77	IC50	0.17	nM	DESMETHYLMIFEPRISTONE
9.77	IC50	0.17	nM	CHEMBL507253
9.77	IC50	0.17	nM	CHEMBL455530
9.74	IC50	0.18	nM	CHEMBL493845
9.74	EC50	0.18	nM	PROGESTERONE
9.74	IC50	0.18	nM	MIFEPRISTONE
9.70	IC50	0.2	nM	CHEMBL3421892
9.70	IC50	0.2	nM	MIFEPRISTONE
9.70	IC50	0.2	nM	ASOPRISNIL
9.70	IC50	0.2	nM	ULIPRISTAL ACETATE
9.70	EC50	0.2	nM	CHEMBL410923
9.70	IC50	0.2	nM	CHEMBL445946
9.70	IC50	0.2	nM	CHEMBL258861

PubChem BioAssay actives

2327 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(8S,11R,13S,14S,17S)-17-hydroxy-13-methyl-11-[4-[methyl(propyl)amino]phenyl]-17-prop-1-ynyl-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-3-one	345895: Antagonist activity at progesterone receptor in human T47D-C124 cells transfected with luciferase gene linked to MMTV promoter assessed as inhibition of progesterone-induced luciferase transactivation activity after 24 hrs	ic50	<0.0001	uM
2-chloro-4-[(2-chlorophenyl)methyl-[1-(1-methyltetrazol-5-yl)ethyl]amino]benzonitrile	424663: Agonist activity at progesterone receptor in human T47D cells by alkaline phosphatase release based reporter gene assay	ec50	<0.0001	uM
2-chloro-4-[(2-chlorophenyl)methyl-[1-(1-methyltetrazol-5-yl)propyl]amino]benzonitrile	424663: Agonist activity at progesterone receptor in human T47D cells by alkaline phosphatase release based reporter gene assay	ec50	<0.0001	uM
2-chloro-4-[(2-chlorophenyl)methyl-[1-(4-methyl-1,2,4-triazol-3-yl)propyl]amino]benzonitrile	424663: Agonist activity at progesterone receptor in human T47D cells by alkaline phosphatase release based reporter gene assay	ec50	<0.0001	uM
(8S,11R,13S,14S,17S)-17-hydroxy-13-methyl-11-[4-(methylamino)phenyl]-17-prop-1-ynyl-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-3-one	345895: Antagonist activity at progesterone receptor in human T47D-C124 cells transfected with luciferase gene linked to MMTV promoter assessed as inhibition of progesterone-induced luciferase transactivation activity after 24 hrs	ic50	0.0001	uM
5-(3-cyclopentyl-2-sulfanylidene-1H-benzimidazol-5-yl)-1-methylpyrrole-2-carbonitrile	300874: Agonist activity at progesterone receptor expressed in T47D cells by alkaline phosphatase assay	ec50	0.0001	uM
(8S,11R,13S,14S,17S)-17-hydroxy-11-(4-methoxyphenyl)-13-methyl-17-prop-1-ynyl-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-3-one	345893: Antagonist activity at progesterone receptor in human T47D cells assessed as inhibition of progesterone-induced alkaline phosphatase activity after 48 hrs	ic50	0.0001	uM
(8S,11R,13S,14S,17S)-11-[4-[5-(1,3-dioxolan-2-yl)pentyl-methylamino]phenyl]-17-hydroxy-13-methyl-17-prop-1-ynyl-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-3-one	345895: Antagonist activity at progesterone receptor in human T47D-C124 cells transfected with luciferase gene linked to MMTV promoter assessed as inhibition of progesterone-induced luciferase transactivation activity after 24 hrs	ic50	0.0001	uM
(8S,11R,13S,14S,17S)-17-hydroxy-11-[4-[3-hydroxypropyl(methyl)amino]phenyl]-13-methyl-17-prop-1-ynyl-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-3-one	345893: Antagonist activity at progesterone receptor in human T47D cells assessed as inhibition of progesterone-induced alkaline phosphatase activity after 48 hrs	ic50	0.0001	uM
(8S,11R,13S,14S,17S)-17-hydroxy-11-[4-[6-hydroxyhexyl(methyl)amino]phenyl]-13-methyl-17-prop-1-ynyl-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-3-one	345893: Antagonist activity at progesterone receptor in human T47D cells assessed as inhibition of progesterone-induced alkaline phosphatase activity after 48 hrs	ic50	0.0001	uM
6-[4-[(8S,11R,13S,14S,17S)-17-hydroxy-13-methyl-3-oxo-17-prop-1-ynyl-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-11-yl]-N-methylanilino]hexanal	345893: Antagonist activity at progesterone receptor in human T47D cells assessed as inhibition of progesterone-induced alkaline phosphatase activity after 48 hrs	ic50	0.0001	uM
5-(4,4-dimethyl-2-sulfanylidene-1H-3,1-benzoxazin-6-yl)-1-methylpyrrole-2-carbonitrile	326395: Agonist activity at human PR expressed in human T47D cells assessed as stimulation of alkaline phosphatase	ec50	0.0001	uM
Mometasone Furoate	162459: Dissociation constant for progesterone receptor	kd	0.0001	uM
(6S,9S,10R,13S,14S,17R)-17-acetyl-6,10,13-trimethyl-17-(2-oxopropyl)-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-3-one	161800: Effective concentration for agonist activity towards human progesterone receptor (hPR) using the cotransfection assay in CV-1 cells	ec50	0.0001	uM
(8S,11R,13S,14S)-11-[4-(6-methoxy-3-pyridinyl)phenyl]-13-methylspiro[1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthrene-17,2’-cyclopentane]-1’,3-dione	323987: Agonist activity at human PRB expressed in CHO cells	ec50	0.0001	uM
(8S,11R,13S,14S,16R,17S)-17-(cyclopropanecarbonyl)-11-[4-(6-methoxy-3-pyridinyl)phenyl]-13,16-dimethyl-2,6,7,8,11,12,14,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-3-one	323987: Agonist activity at human PRB expressed in CHO cells	ec50	0.0001	uM
(8S,11R,13S,14S,17S)-17-(cyclopropanecarbonyl)-13,17-dimethyl-11-(4-pyridin-3-ylphenyl)-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-3-one	323989: Antagonist activity at human PRB expressed in CHO cells assessed as inhibition of Org 2058 induced-transactivation	ic50	0.0001	uM
2-chloro-4-[(2-chlorophenyl)methyl-[1-(4-methyl-1,2,4-triazol-3-yl)butyl]amino]benzonitrile	424663: Agonist activity at progesterone receptor in human T47D cells by alkaline phosphatase release based reporter gene assay	ec50	0.0001	uM
methyl (3S)-3-[3-chloro-N-[(2-chlorophenyl)methyl]-4-cyanoanilino]pyrrolidine-1-carboxylate	455831: Agonist activity at PR in human T47D cells	ec50	0.0001	uM
Fulvestrant	1251783: Antagonist activity at progesterone receptor in human MCF cells assessed as estradiol-induced receptor response	ic50	0.0002	uM
(8S,11R,13S,14S,16R,17S)-17-(cyclopropanecarbonyl)-13,16-dimethyl-11-(4-pyridin-3-ylphenyl)-2,6,7,8,11,12,14,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-3-one	323987: Agonist activity at human PRB expressed in CHO cells	ec50	0.0002	uM
Ulipristal Acetate	323989: Antagonist activity at human PRB expressed in CHO cells assessed as inhibition of Org 2058 induced-transactivation	ic50	0.0002	uM
2-[[1-(2-chloro-5-fluorophenyl)cyclobutyl]methyl]-3,3,3-trifluoro-2-hydroxy-N-(4-methyl-1-oxo-2,3-benzoxazin-6-yl)propanamide	1203076: Binding affinity to human PR	ic50	0.0002	uM
4-methyl-5-(2,4,4-trimethyl-1,2-dihydro-3,1-benzoxazin-6-yl)thiophene-2-carbonitrile	161815: Agonistic activity against progesterone receptor in alkaline phosphatase assay using human T47D breast carcinoma cell line	ec50	0.0002	uM
4-O-[6-[4-[(8S,11R,13S,14S,17S)-17-hydroxy-13-methyl-3-oxo-17-prop-1-ynyl-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-11-yl]-N-methylanilino]hexyl] 1-O-methyl butanedioate	345893: Antagonist activity at progesterone receptor in human T47D cells assessed as inhibition of progesterone-induced alkaline phosphatase activity after 48 hrs	ic50	0.0002	uM
methyl 3-[4-[(8S,11R,13S,14S,17S)-17-hydroxy-13-methyl-3-oxo-17-prop-1-ynyl-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-11-yl]-N-methylanilino]propanoate	345893: Antagonist activity at progesterone receptor in human T47D cells assessed as inhibition of progesterone-induced alkaline phosphatase activity after 48 hrs	ic50	0.0002	uM
3-(4-chlorophenyl)-1-[4-[(8S,11R,13S,14S,17S)-17-hydroxy-13-methyl-3-oxo-17-prop-1-ynyl-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-11-yl]phenyl]-1-methylthiourea	345893: Antagonist activity at progesterone receptor in human T47D cells assessed as inhibition of progesterone-induced alkaline phosphatase activity after 48 hrs	ic50	0.0002	uM
(8S,11R,13S,14S,17S)-11-[4-[hexyl(methyl)amino]phenyl]-17-hydroxy-13-methyl-17-prop-1-ynyl-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-3-one	345895: Antagonist activity at progesterone receptor in human T47D-C124 cells transfected with luciferase gene linked to MMTV promoter assessed as inhibition of progesterone-induced luciferase transactivation activity after 24 hrs	ic50	0.0002	uM
(8S,13S,14S,17S)-13,17-dimethyl-17-propanoyl-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-3-one	1417058: Agonist activity at GAL4 DNA-binding domain fused PR (unknown origin) ligand binding domain expressed in UAS-bla HEK 293T cells assessed as beta-lactamase transcriptional activation by FRET-based GeneBLAzer assay	ic50	0.0002	uM
(8S,11R,13S,14S,16R,17S)-17-(cyclopropanecarbonyl)-16-ethyl-13-methyl-11-(4-pyridin-3-ylphenyl)-2,6,7,8,11,12,14,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-3-one	323987: Agonist activity at human PRB expressed in CHO cells	ec50	0.0002	uM
(8R,9S,11S,13S,14S,17R)-11-[4-(dimethylamino)phenyl]-13-methyl-3’-methylidenespiro[1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthrene-17,2’-oxolane]-3-one	323990: Antagonist activity at human PRB expressed in CHO cells assessed as inhibition of Org 2058 induced-transactivation relative to Org 31710	ic50	0.0002	uM
(8S,11R,13S,14S,17S)-11-[4-(dimethylamino)phenyl]-13-methylspiro[1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthrene-17,2’-cyclopentane]-1’,3-dione	323990: Antagonist activity at human PRB expressed in CHO cells assessed as inhibition of Org 2058 induced-transactivation relative to Org 31710	ic50	0.0002	uM
5-(4-chlorophenyl)-9-fluoro-2,2,4-trimethyl-1,5-dihydrochromeno[3,4-f]quinoline	162298: The binding affinity measured using baculovirus-expressed hPR-A in sf21 cells.	ki	0.0003	uM
4-(2,4,4-trimethyl-1,2-dihydro-3,1-benzoxazin-6-yl)thiophene-2-carbonitrile	161815: Agonistic activity against progesterone receptor in alkaline phosphatase assay using human T47D breast carcinoma cell line	ec50	0.0003	uM
6-(3-chlorophenyl)-4-methyl-4-prop-2-enyl-1H-3,1-benzoxazine-2-thione	208678: Effective concentration on alkaline phosphatase activity in human T47D breast carcinoma cell line.	ec50	0.0003	uM
9-chloro-5-(3-fluorophenyl)-2,2,4-trimethyl-1,5-dihydrochromeno[3,4-f]quinoline	162298: The binding affinity measured using baculovirus-expressed hPR-A in sf21 cells.	ki	0.0003	uM
(1S,3aR,3bS,10R,11aS)-10-[4-(dimethylamino)phenyl]-1-[2-(4-fluorophenyl)ethynyl]-1-hydroxy-11a-methyl-3,3a,3b,5,8,9,10,11-octahydro-2H-indeno[4,5-c]isochromen-7-one	294498: Antagonist activity at human progesterone receptor assessed as inhibition of alkaline phosphatase activity in human T47D cells	ic50	0.0003	uM
3-fluoro-5-(2,4,4-trimethyl-1,2-dihydro-3,1-benzoxazin-6-yl)benzonitrile	161814: Agonist activity against Progesterone receptor (PR) in transcriptional activation assay in human T47D breast carcinoma cell line	ec50	0.0003	uM
N-[1-[(2S)-butan-2-yl]-3-(4-cyanophenyl)indol-6-yl]methanesulfonamide	570052: Displacement of [3H]methyltrienolone from human progesterone receptor expressed in HEK293 cells	ki	0.0003	uM
4-[6-[4-[(8S,11R,13S,14S,17S)-17-hydroxy-13-methyl-3-oxo-17-prop-1-ynyl-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-11-yl]-N-methylanilino]hexoxy]-4-oxobutanoic acid	345893: Antagonist activity at progesterone receptor in human T47D cells assessed as inhibition of progesterone-induced alkaline phosphatase activity after 48 hrs	ic50	0.0003	uM
8-[4-[(8S,11R,13S,14S,17S)-17-hydroxy-13-methyl-3-oxo-17-prop-1-ynyl-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-11-yl]-N-methylanilino]octanoic acid	345893: Antagonist activity at progesterone receptor in human T47D cells assessed as inhibition of progesterone-induced alkaline phosphatase activity after 48 hrs	ic50	0.0003	uM
3-(4-chlorophenyl)-1-[4-[(8S,11R,13S,14S,17S)-17-hydroxy-13-methyl-3-oxo-17-prop-1-ynyl-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-11-yl]phenyl]-1-methylurea	345893: Antagonist activity at progesterone receptor in human T47D cells assessed as inhibition of progesterone-induced alkaline phosphatase activity after 48 hrs	ic50	0.0003	uM
(8S,11R,13S,14S,17S)-11-(4-acetylphenyl)-2’-ethyl-13-methyl-5’-methylidenespiro[1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthrene-17,4’-1,3-oxazole]-3-one	309724: Antagonist activity at progesterone receptor expressed in human T47D cells assessed as inhibition of promegestone-induced alkaline phosphatase activity	ic50	0.0003	uM
(8S,11R,13S,14S)-13-methyl-11-(4-pyridin-3-ylphenyl)spiro[1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthrene-17,2’-cyclopentane]-1’,3-dione	323987: Agonist activity at human PRB expressed in CHO cells	ec50	0.0003	uM
2-chloro-4-[(2-chlorophenyl)methyl-[(3S)-5-oxo-1-propan-2-ylpyrrolidin-3-yl]amino]benzonitrile	434184: Agonist activity at progesterone receptor in human T47D cells assessed as inhibition of progesterone-induced alkaline phosphatase activity	ec50	0.0003	uM
2-chloro-4-[(2-chloro-5-fluorophenyl)methyl-[(3S)-1-ethyl-5-oxopyrrolidin-3-yl]amino]benzonitrile	434184: Agonist activity at progesterone receptor in human T47D cells assessed as inhibition of progesterone-induced alkaline phosphatase activity	ec50	0.0003	uM
(1S,12S,15S,20R)-15-hydroxy-1,16,16,20-tetramethyl-3-azapentacyclo[10.8.0.02,10.04,9.015,20]icosa-2(10),4,6,8-tetraen-17-one	469431: Activation of progesterone receptor in human T47D cells after 20 hrs by PRE-tagged luciferase reporter gene assay	ec50	0.0003	uM
(1S,2S,5R,6R,9R)-9-[4-(dimethylamino)phenyl]-5-hydroxy-6-methyl-5-prop-1-en-2-yl-8-oxatetracyclo[8.8.0.02,6.011,16]octadeca-10,15-dien-14-one	426409: Antagonist activity at progesterone receptor in human T47D cells assessed as inhibition of progesterone-induced alkaline phosphatase activity	ic50	0.0003	uM
2-chloro-4-[(2-chlorophenyl)methyl-[(3S)-1-methyl-5-oxopyrrolidin-3-yl]amino]benzonitrile	434184: Agonist activity at progesterone receptor in human T47D cells assessed as inhibition of progesterone-induced alkaline phosphatase activity	ec50	0.0003	uM
5-(3-chlorophenyl)-2,2,4-trimethyl-1,5-dihydrochromeno[3,4-f]quinoline	162297: The binding affinity on Human progesterone receptor (hPR-A) using progesterone as radioligand.	ki	0.0004	uM

CTD chemical–gene interactions

383 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	increases reaction, increases activity, decreases reaction, increases expression, affects phosphorylation (+7 more)	109
Fulvestrant	affects binding, decreases activity, decreases reaction, increases expression, decreases expression	28
bisphenol A	increases phosphorylation, affects reaction, affects expression, increases expression, affects cotreatment (+4 more)	27
Progesterone	increases expression, affects expression, affects phosphorylation, increases activity, increases reaction (+6 more)	26
Tamoxifen	increases expression, affects reaction, affects response to substance, decreases reaction, decreases expression (+4 more)	16
Mifepristone	affects activity, affects binding, increases activity, increases reaction, increases expression (+4 more)	13
Tetrachlorodibenzodioxin	affects cotreatment, decreases phosphorylation, increases response to substance, decreases expression, increases reaction (+4 more)	10
Genistein	decreases reaction, increases expression, increases reaction, decreases expression	10
o,p’-DDT	decreases reaction, increases expression, affects binding, increases activity	8
Resveratrol	increases reaction, increases expression, decreases reaction, affects reaction, decreases activity (+2 more)	8
Promegestone	decreases reaction, increases activity, increases reaction, increases uptake, affects binding	8
trichostatin A	decreases reaction, affects cotreatment, affects expression, increases expression, decreases expression	6
Dichlorodiphenyl Dichloroethylene	affects binding, decreases reaction, increases activity, increases expression	6
Diethylstilbestrol	decreases reaction, increases expression	6
bisphenol Z	affects binding, decreases reaction, increases activity, increases expression	5
bisphenol AF	affects binding, decreases reaction, increases reaction, increases expression	5
Decitabine	affects expression, increases expression, decreases reaction, increases activity, affects cotreatment	5
DDT	affects binding, decreases reaction, increases activity, increases expression, decreases expression	5
Endosulfan	affects binding, decreases reaction, increases expression, decreases expression, affects cotreatment	5
Zearalenone	increases expression, increases reaction, decreases reaction, affects binding, increases activity	5
Raloxifene Hydrochloride	affects cotreatment, increases expression, decreases reaction, decreases expression	5
afimoxifene	decreases reaction, increases expression, decreases expression, affects cotreatment, increases reaction	4
sodium arsenite	affects activity, decreases reaction, increases expression, decreases activity, decreases expression	4
beta-hexachlorocyclohexane	decreases reaction, increases expression, increases activity	4
nonylphenol	decreases activity, affects binding, decreases reaction, increases expression	4
butylparaben	increases expression, decreases reaction	4
bisphenol B	decreases reaction, increases expression, affects binding	4
bisphenol S	increases expression, decreases reaction	4
Doxorubicin	increases expression, affects binding, decreases activity, decreases expression	4
Medroxyprogesterone Acetate	decreases reaction, increases expression, affects binding, increases reaction, decreases expression (+1 more)	4

ChEMBL screening assays

643 unique, capped per target: 401 binding, 231 functional, 11 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1002263	Binding	Inhibition of human progesterone receptor	Discovery of betamethasone 17alpha-carbamates as dissociated glucocorticoid receptor modulators in the rat. — Bioorg Med Chem
CHEMBL1010302	Functional	Agonist activity at human progesterone receptor	A tissue-selective nonsteroidal progesterone receptor modulator: 7,9-difluoro-5-(3-methylcyclohex-2-enyl)-2,2,4-trimethyl-1,2-dihydrochromeno[3,4-f]quinoline. — J Med Chem
CHEMBL4028146	ADMET	Antagonist activity at PR (unknown origin) by Gal4-based cellular assay	Identification of Morpholino-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-ones as Nonsteroidal Mineralocorticoid Antagonists. — J Med Chem

Cellosaurus cell lines

15 cell lines: 9 cancer cell line, 3 embryonic stem cell, 2 telomerase immortalized cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A5H4	SEES3-1V human PGR, clone1	Embryonic stem cell	Male
CVCL_A5H5	SEES3-1V human PGR, clone2	Embryonic stem cell	Male
CVCL_A5H6	SEES3-1V human PGR, clone3	Embryonic stem cell	Male
CVCL_B2AJ	Abcam HeLa PGR KO	Cancer cell line	Female
CVCL_B8MH	Abcam HCT 116 PGR KO	Cancer cell line	Male
CVCL_B9A8	Abcam MCF-7 PGR KO	Cancer cell line	Female
CVCL_B9PN	Abcam A-549 PGR KO	Cancer cell line	Male
CVCL_C3G7	Ishikawa 3-H-12 PRA-14	Cancer cell line	Female
CVCL_C3G8	Ishikawa 3-H-12 PRB-59	Cancer cell line	Female
CVCL_LB12	PathHunter U2OS PRalpha Protein Interaction	Cancer cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.