FKBP5

Summary

FKBP5 (FKBP prolyl isomerase 5, HGNC:3721) is a protein-coding gene on chromosome 6p21.31, encoding Peptidyl-prolyl cis-trans isomerase FKBP5 (Q13451). Immunophilin protein with PPIase and co-chaperone activities.

The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. This encoded protein is a cis-trans prolyl isomerase that binds to the immunosuppressants FK506 and rapamycin. It is thought to mediate calcineurin inhibition. It also interacts functionally with mature hetero-oligomeric progesterone receptor complexes along with the 90 kDa heat shock protein and P23 protein. This gene has been found to have multiple polyadenylation sites. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 2289 — RefSeq curated summary.

At a glance

• GWAS associations: 21
• Clinical variants (ClinVar): 75 total
• Phenotypes (HPO): 2
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_004117

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3721
Approved symbol	FKBP5
Name	FKBP prolyl isomerase 5
Location	6p21.31
Locus type	gene with protein product
Status	Approved
Aliases	FKBP51, FKBP54, PPIase, P54, Ptg-10
Ensembl gene	ENSG00000096060
Ensembl biotype	protein_coding
OMIM	602623
Entrez	2289

Gene structure

Transcript identifiers

Ensembl transcripts: 73 — 73 protein_coding

ENST00000357266, ENST00000536438, ENST00000539068, ENST00000542713, ENST00000893093, ENST00000893094, ENST00000893095, ENST00000893096, ENST00000893097, ENST00000893098, ENST00000893099, ENST00000893100, ENST00000893101, ENST00000893102, ENST00000893103, ENST00000893104, ENST00000893105, ENST00000893106, ENST00000893107, ENST00000893108, ENST00000893109, ENST00000893110, ENST00000893111, ENST00000893112, ENST00000893113, ENST00000893114, ENST00000893115, ENST00000893116, ENST00000893117, ENST00000893118, ENST00000893119, ENST00000893120, ENST00000893121, ENST00000893122, ENST00000893123, ENST00000893124, ENST00000893125, ENST00000893127, ENST00000893128, ENST00000893131, ENST00000893132, ENST00000893134, ENST00000893136, ENST00000893138, ENST00000893140, ENST00000893142, ENST00000893144, ENST00000893146, ENST00000893148, ENST00000893150, ENST00000925704, ENST00000956371, ENST00000956372, ENST00000956373, ENST00000956374, ENST00000956375, ENST00000956376, ENST00000956377, ENST00000956378, ENST00000956379, ENST00000956380, ENST00000956381, ENST00000956382, ENST00000956383, ENST00000956384, ENST00000956385, ENST00000956386, ENST00000956387, ENST00000956388, ENST00000956389, ENST00000956390, ENST00000956391, ENST00000956392

RefSeq mRNA: 4 — MANE Select: NM_004117 NM_001145775, NM_001145776, NM_001145777, NM_004117

CCDS: CCDS4808, CCDS54996

Canonical transcript exons

ENST00000357266 — 11 exons

Exon	Start	End
ENSE00000747301	35576994	35577233
ENSE00000747302	35580036	35580221
ENSE00000747303	35587034	35587117
ENSE00000747304	35591130	35591220
ENSE00000747342	35619096	35619210
ENSE00000747346	35637014	35637158
ENSE00001354861	35573590	35575942
ENSE00001354888	35688804	35688915
ENSE00001370159	35642720	35642843
ENSE00001391213	35620132	35620274
ENSE00003659116	35597248	35597404

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 99.09.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 41.1849 / max 2088.2821, expressed in 1761 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
73303	35.8449	1723
73304	4.8536	1364
73308	0.1705	47
73307	0.1642	58
73294	0.0789	31
73302	0.0728	31

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of stomach	UBERON:0001199	99.09	gold quality
pericardium	UBERON:0002407	98.89	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.72	gold quality
right lung	UBERON:0002167	98.61	gold quality
skin of hip	UBERON:0001554	98.58	gold quality
upper leg skin	UBERON:0004262	98.48	gold quality
gastrocnemius	UBERON:0001388	98.40	gold quality
left uterine tube	UBERON:0001303	98.22	gold quality
biceps brachii	UBERON:0001507	98.12	gold quality
corpus epididymis	UBERON:0004359	98.03	gold quality
synovial joint	UBERON:0002217	98.02	gold quality
muscle of leg	UBERON:0001383	98.00	gold quality
penis	UBERON:0000989	97.88	gold quality
tibia	UBERON:0000979	97.74	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.62	gold quality
nipple	UBERON:0002030	97.55	gold quality
lower lobe of lung	UBERON:0008949	97.52	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.52	gold quality
body of tongue	UBERON:0011876	97.50	gold quality
lower esophagus	UBERON:0013473	97.47	gold quality
left coronary artery	UBERON:0001626	97.27	gold quality
superficial temporal artery	UBERON:0001614	97.19	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.17	gold quality
coronary artery	UBERON:0001621	97.06	gold quality
right ovary	UBERON:0002118	97.06	gold quality
parietal pleura	UBERON:0002400	96.92	gold quality
ectocervix	UBERON:0012249	96.89	gold quality
lymph node	UBERON:0000029	96.75	gold quality
heart right ventricle	UBERON:0002080	96.75	gold quality
popliteal artery	UBERON:0002250	96.74	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-GEOD-131882	yes	3998.97
E-CURD-119	yes	3874.30
E-CURD-97	yes	1490.16
E-MTAB-8559	yes	861.74
E-HCAD-35	yes	37.42
E-MTAB-8410	yes	20.16
E-HCAD-25	yes	15.91
E-GEOD-99795	no	390.65
E-MTAB-7303	no	50.99
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, CLOCK, MECP2, NFKBIA, NR3C1, NR3C2, PGR, TSC22D3

miRNA regulators (miRDB)

111 targeting FKBP5, 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-3613-3P	100.00	76.36	7965
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867

Literature-anchored findings (GeneRIF, showing 40)

• Overexpression in idioppathic myelofibrosis regulates the growth factor independence of megakaryocyte progenitors (PMID:12351405)
• description of crystallographic structure of human FKBP51 and its comparison to squirrel monkey FKBP51 (PMID:12538866)
• increased expression of FKBP51 by progestin may attenuate progestin responsiveness in hormone-conditioned cells. (PMID:12746298)
• FKBP51 is constitutively expressed in non-neoplastic haematopoiesis. FKBP51 expression by total bone marrow cells & megakaryocytes was not significantly different in idiopathic myelofibrosis. FKBP51 localised to myeloid progenitor cells & megakaryocytes. (PMID:15089760)
• FK506-binding proteins 51 and 52 differentially regulate dynein interaction and nuclear translocation of the glucocorticoid receptor (PMID:15591061)
• The rs3800373 polymorphism in the FKBP5 gene explains 14% of the variation in peritraumatic dissociation in injured children. (PMID:16088328)
• The distal enhancer complex and basal transcription apparatus communicate indirectly with one another, implicating a regulatory mechanism that has not been previously appreciated for androgen receptor target genes. (PMID:16210365)
• coumermycin A1, a coumarin structurally related to novobiocin, interferes with dimerization of the Hsp90 C-terminal domain of FKBP51 (PMID:16421106)
• There is no association between FKBP5 polymorphism and lifetime depressive episodes. (PMID:17721930)
• FKBP51 isoforms found on the gel map were linked to alternative promoter usage on the genetic level, successfully correlating both the specific proteomic and genomic findings. (PMID:17960574)
• Five SNPs from the FKBP5 gene (rs4713902, rs7757037, rs9296158, rs3800373 and rs9380525) showed evidence for association with bipolar disorder in a family sample with 317 bipolar pedigrees and 554 affected offspring. (PMID:18180755)
• The present study aimed at studying the associated FKBP5 markers in the ethnically diverse Sequenced Treatment Alternatives to Relieve Depression (STAR*D) sample of non-hospitalized patients treated with citalopram. (PMID:18191112)
• In conclusion, there are differences of HADS anxiety score and FKBP5 mRNA expression in the leukocytes across the menstrual cycle but there is no correlation between anxiety scores and FKBP5 mRNA. (PMID:18291582)
• FKBP5 plays an important role in glioma growth and chemoresistance through regulating signal transduction of the NF-kappaB pathway. (PMID:18320068)
• Genetic variation in the FKBP5 gene may alter sensitization of the stress-response pathway during development, placing those individuals who have had significant child abuse at significant risk for PTSD. (PMID:18349090)
• Normal epithelial cells & adenocarcinoma in the human colon express FKBP51 without no significant differences between them. FKBP51 suppresses colorectal adenocarcinoma proliferation, possibly by suppressing the glucocorticoid receptors. (PMID:18443959)
• WAFL may be connected to innate immune-host responses. (PMID:18654788)
• Homozygous carriers of FKBP5 minor allele showed insufficient cortisol and increased anxiety after psychosocial stress. Carriers are at risk of chronically elevated cortisol levels after repeated stress, risk factor for stress-related diseases. (PMID:18702710)
• The increase in hippocampal GR level and low concentration of FKBP51 in the frontal cortex may be responsible for enhanced glucocorticoid action in depression. (PMID:19195790)
• an increase in FKBP51 at both the transcript (FKBP5) and protein level correlated with major depressive disorder (PMID:19199039)
• Within the DR52 supertype, the FKBP5*T-DR6 haplotype is associated with resistance to endogenous and exogenous glucocorticoids (PMID:19233472)
• knockdown of FKBP5, coding for immunophilin FKBP51, was associated with increased baseline glucocorticoid receptor nuclear localization (PMID:19545546)
• overshooting induction of FKBP5 following cortisol release in response to a stressor would lead to an impaired negative feedback of cortisol release and thus prolonged elevations of cortisol following a stressor. (PMID:19560279)
• FKBP5 polymorphisms do not have a role in antidepressant response in geriatric depression (PMID:19676097)
• FK506-binding protein 51 controls Rx-induced apoptosis in melanoma and correlates with malignity of the lesions, provides a novel potential target for signaling therapies of advanced disease. (PMID:19696786)
• FKBP51 affects cancer cell response to chemotherapy by negatively regulating Akt. (PMID:19732725)
• Recently reported genetic association studies indicate that these effects may be mediated, in part, by genexenvironment interactions involving polymorphisms within two key genes, CRHR1 and FKBP5. (PMID:19750552)
• A single nucleotide polymorphism in FKBP5 (rs1360780) predicts disease remission to antidepressant treatment. (PMID:19924111)
• rs1360780TT and rs3800373GG genotypes associated with suicidal events in adolescents with depression unresponsive to second generation antidepressants (PMID:20008943)
• Data show that disruption of FKBP51 and Cyp40 in AI C4-2 cells caused only a small reduction in proliferation. (PMID:20023700)
• Several single nucleotide polymorphisms of FKBP5 are found in association with disease status, and the intermediate phenotype of hippocampal volume is associated with clinical unipolar depression. (PMID:20047716)
• FKBP51 stimulates recruitment of the cochaperone p23 to Hsp90, forming an FKBP51-Hsp90-p23 complex. In cells, FKBP51 expression promotes complex association with AR and increases the number of AR molecules that undergo androgen binding. (PMID:20048054)
• This study showed that theFK506-binding protein 51, which possesses both an Hsp90-interacting tetratricopeptide domain and a peptidyl-prolyl cis-trans isomerase (PPIase) domain, prevents tau clearance and regulates its phosphorylation status (PMID:20071522)
• These data suggest that childhood trauma and variants of the FKBP5 gene may interact to increase the risk for attempting suicide. (PMID:20090668)
• Data indicate that activation of the FKBP51 locus by glucocorticoids in vivo is triggered by the loading of GR to enhancers at about 34 kb 5’ and about 87 kb 3’ of the transcription start site. (PMID:20093418)
• enhanced expression of FKBP5 in bone marrow CD34+ cells might be an intrinsic abnormality of rheumatoid arthritis bone marrow CD34+ cells (PMID:20346245)
• This study provides further evidence of a gene x environment effect of FKBP5 and childhood abuse on the risk for PTSD in African Americans. (PMID:20393453)
• we found a significant interaction effect for insecure-resistant attachment and FKBP5 rs1360780, indicating a double-risk for heightened cortisol reactivity levels in infants (PMID:20547006)
• FKBP51 exhibited strong interaction with glucocorticoid receptor and progesterone receptors. (PMID:20661446)
• This meta-analysis demonstrates that treatment response in patients with mood disorders is associated with FKBP5 gene rs4713916 polymorphism, but not rs1360780 and rs3800373. (PMID:20709156)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	fkbp5	ENSDARG00000028396
mus_musculus	Fkbp5	ENSMUSG00000024222
rattus_norvegicus	Fkbp5	ENSRNOG00000022523
drosophila_melanogaster	Fkbp39	FBGN0013269
caenorhabditis_elegans		WBGENE00001429
caenorhabditis_elegans	fkb-5	WBGENE00001430

Paralogs (18): FKBP4 (ENSG00000004478), FKBP6 (ENSG00000077800), FKBP7 (ENSG00000079150), FKBP1A (ENSG00000088832), FKBP3 (ENSG00000100442), FKBP8 (ENSG00000105701), FKBP14 (ENSG00000106080), FKBP15 (ENSG00000119321), FKBP1B (ENSG00000119782), FKBP9 (ENSG00000122642), TTC9 (ENSG00000133985), FKBP11 (ENSG00000134285), FKBP10 (ENSG00000141756), TTC9C (ENSG00000162222), FKBP2 (ENSG00000173486), TTC9B (ENSG00000174521), FKBP1C (ENSG00000198225), FKBPL (ENSG00000204315)

Protein

Protein identifiers

Peptidyl-prolyl cis-trans isomerase FKBP5 — Q13451 (reviewed: Q13451)

Alternative names: 51 kDa FK506-binding protein, 54 kDa progesterone receptor-associated immunophilin, Androgen-regulated protein 6, FF1 antigen, FK506-binding protein 5, FKBP54, HSP90-binding immunophilin, Rotamase

All UniProt accessions (1): Q13451

UniProt curated annotations — full annotation on UniProt →

Function. Immunophilin protein with PPIase and co-chaperone activities. Component of unligated steroid receptors heterocomplexes through interaction with heat-shock protein 90 (HSP90). Plays a role in the intracellular trafficking of heterooligomeric forms of steroid hormone receptors maintaining the complex into the cytoplasm when unliganded. Acts as a regulator of Akt/AKT1 activity by promoting the interaction between Akt/AKT1 and PHLPP1, thereby enhancing dephosphorylation and subsequent activation of Akt/AKT1. Interacts with IKBKE and IKBKB which facilitates IKK complex assembly leading to increased IKBKE and IKBKB kinase activity, NF-kappa-B activation, and IFN production.

Subunit / interactions. Part of a heteromultimeric cytoplasmic complex with HSP90AA1, HSPA1A/HSPA1B and steroid receptors. Upon ligand binding dissociates from the complex and FKBP4 takes its place. Interacts with functionally mature heterooligomeric progesterone receptor complexes along with HSP90 and TEBP. Interacts with NR3C1. Interacts with Akt/AKT1 and PHLPP1; enhancing dephosphorylation and subsequent activation of Akt/AKT1. Interacts with IFI44L; this interaction modulates the kinase activity of IKBKB and IKBKE. Interacts with IKBKB and IKBKE.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Widely expressed, enriched in testis compared to other tissues.

Post-translational modifications. Acetylation impairs ability to promote interaction between Akt/AKT1 and PHLPP1. Deacetylation by SIRT7 promotes interaction between Akt/AKT1 and PHLPP1, leading to suppress Akt/AKT1 activation. Ubiquitinated, leading to degradation in a proteasome-dependent manner. Deubiquitinated by USP49, leading to stabilization.

Activity regulation. Inhibited by both FK506 and rapamycin.

Induction. By androgen.

Isoforms (2)

UniProt ID	Names	Canonical?
Q13451-1	1	yes
Q13451-2	2

RefSeq proteins (4): NP_001139247, NP_001139248, NP_001139249, NP_004108* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001179	PPIase_FKBP_dom	Domain
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR019734	TPR_rpt	Repeat
IPR046357	PPIase_dom_sf	Homologous_superfamily
IPR050754	FKBP4/5/8-like	Family

Pfam: PF00254, PF00515, PF13181

Catalyzed reactions (Rhea), 1 shown:

• [protein]-peptidylproline (omega=180) = [protein]-peptidylproline (omega=0) (RHEA:16237)

UniProt features (55 total): strand 16, helix 15, modified residue 5, mutagenesis site 4, turn 4, repeat 3, domain 2, splice variant 2, region of interest 2, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

138 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7AOT	X-RAY DIFFRACTION	0.85
7APW	X-RAY DIFFRACTION	0.89
8R5K	X-RAY DIFFRACTION	0.89
7APS	X-RAY DIFFRACTION	0.94
3O5Q	X-RAY DIFFRACTION	0.96
6TX6	X-RAY DIFFRACTION	0.98
8CHN	X-RAY DIFFRACTION	0.99
3O5P	X-RAY DIFFRACTION	1
4DRQ	X-RAY DIFFRACTION	1
5OBK	X-RAY DIFFRACTION	1
8CHP	X-RAY DIFFRACTION	1
8CHQ	X-RAY DIFFRACTION	1.01
4JFM	X-RAY DIFFRACTION	1.02
4TX0	X-RAY DIFFRACTION	1.03
4JFI	X-RAY DIFFRACTION	1.05
6TX4	X-RAY DIFFRACTION	1.06
4DRN	X-RAY DIFFRACTION	1.07
4JFJ	X-RAY DIFFRACTION	1.08
4W9Q	X-RAY DIFFRACTION	1.08
6TX5	X-RAY DIFFRACTION	1.08
7APQ	X-RAY DIFFRACTION	1.09
3O5R	X-RAY DIFFRACTION	1.1
4DRO	X-RAY DIFFRACTION	1.1
7R0L	X-RAY DIFFRACTION	1.1
8BA6	X-RAY DIFFRACTION	1.1
8CHR	X-RAY DIFFRACTION	1.1
6TX7	X-RAY DIFFRACTION	1.13
7APT	X-RAY DIFFRACTION	1.13
7BA0	X-RAY DIFFRACTION	1.14
3O5O	X-RAY DIFFRACTION	1.15

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13451-F1	92.77	0.88

Functional residue map

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

Post-translational modifications (5): 13, 28, 155, 445, 1

Mutagenesis-validated functional residues (4):

Position	Phenotype
28	mimics acetylation; impaired interaction with akt1 and phlpp1; when associated with q-155.
28	decreased acetylation; promotes interaction with akt1 and phlpp1; when associated with r-155.
155	mimics acetylation; impaired interaction with akt1 and phlpp1; when associated with q-28.
155	decreased acetylation; promotes interaction with akt1 and phlpp1; when associated with r-28.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-3371497	HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand
R-HSA-8939211	ESR-mediated signaling
R-HSA-9022699	MECP2 regulates neuronal receptors and channels
R-HSA-9909505	Modulation of host responses by IFN-stimulated genes

MSigDB gene sets: 376 (showing top): RNGTGGGC_UNKNOWN, BROWNE_HCMV_INFECTION_4HR_UP, MYAATNNNNNNNGGC_UNKNOWN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, E2F4DP1_01, GOBP_RESPONSE_TO_COCAINE, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, BROWNE_HCMV_INFECTION_16HR_UP, LHX3_01, PID_REG_GR_PATHWAY, ACTGCAG_MIR173P, COUP_01, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, CHEN_LVAD_SUPPORT_OF_FAILING_HEART_UP, E2F1DP1_01

GO Biological Process (6): protein folding (GO:0006457), response to bacterium (GO:0009617), response to cocaine (GO:0042220), negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051898), response to alcohol (GO:0097305), phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0043491)

GO Molecular Function (6): peptidyl-prolyl cis-trans isomerase activity (GO:0003755), FK506 binding (GO:0005528), protein-macromolecule adaptor activity (GO:0030674), heat shock protein binding (GO:0031072), protein binding (GO:0005515), isomerase activity (GO:0016853)

GO Cellular Component (6): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020), extracellular exosome (GO:0070062), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Cellular responses to stress	1
Signaling by Nuclear Receptors	1
Transcriptional Regulation by MECP2	1
Interferon Signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
response to oxygen-containing compound	2
protein binding	2
cellular process	1
protein maturation	1
response to other organism	1
response to alkaloid	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
negative regulation of intracellular signal transduction	1
intracellular signaling cassette	1
cis-trans isomerase activity	1
catalytic activity, acting on a protein	1
macrolide binding	1
molecular adaptor activity	1
binding	1
catalytic activity	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
extracellular vesicle	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

3846 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FKBP5	NR3C1	P04150	998
FKBP5	HSP90AA1	P07900	996
FKBP5	HSP90AB1	P08238	995
FKBP5	PHLPP1	O60346	992
FKBP5	HSPA4	P34932	989
FKBP5	DNAJB1	P25685	928
FKBP5	AKT1	P31749	907
FKBP5	PGR	P06401	903
FKBP5	BCL2A1	Q16548	891
FKBP5	CHUK	O15111	872
FKBP5	SGK1	O00141	826
FKBP5	SLC6A4	P31645	787
FKBP5	CLCA1	A8K7I4	768
FKBP5	PTGES3	Q15185	763
FKBP5	SERPINB2	P05120	742

IntAct

363 interactions, top by confidence:

A	B	Type	Score
CDK9	CCNT1	psi-mi:“MI:0914”(association)	0.980
PRKAA1	PRKAB2	psi-mi:“MI:0914”(association)	0.950
STK11	FKBP5	psi-mi:“MI:0914”(association)	0.910
CSNK1A1	FAM83G	psi-mi:“MI:0914”(association)	0.900
FKBP5	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.890
HSP90AB1	FKBP5	psi-mi:“MI:0407”(direct interaction)	0.890
FKBP5	HSP90AA1	psi-mi:“MI:0407”(direct interaction)	0.800
FKBP5	CHUK	psi-mi:“MI:0915”(physical association)	0.780
NS	PIK3R2	psi-mi:“MI:0914”(association)	0.750
STK11	HSP90AA1	psi-mi:“MI:0914”(association)	0.740
CDK9	AIP	psi-mi:“MI:0914”(association)	0.730
FKBP5	MAPT	psi-mi:“MI:0407”(direct interaction)	0.700
FKBP5	MCMBP	psi-mi:“MI:0915”(physical association)	0.680

BioGRID (691): HSP90AA1 (Reconstituted Complex), FKBP5 (Affinity Capture-MS), FKBP5 (Affinity Capture-MS), FKBP5 (Affinity Capture-MS), FKBP5 (Affinity Capture-MS), FKBP5 (Affinity Capture-MS), FKBP5 (Affinity Capture-MS), FKBP5 (Affinity Capture-MS), FKBP5 (Affinity Capture-MS), FKBP5 (Affinity Capture-MS), FKBP5 (Affinity Capture-MS), FKBP5 (Affinity Capture-MS), FKBP5 (Affinity Capture-MS), FKBP5 (Affinity Capture-MS), FKBP5 (Affinity Capture-MS)

ESM2 similar proteins: A0A0P0VG31, A0A2H5Q1B8, A4K2V0, A8XHX1, F1RBN2, O14085, O14217, P19878, P27124, P30416, Q02790, Q06AN9, Q07617, Q13217, Q13451, Q15785, Q20683, Q27968, Q32NU8, Q3KRD5, Q3ZBR5, Q5JNB5, Q5RF88, Q5U2X2, Q5ZI13, Q5ZKQ3, Q64378, Q68FQ7, Q6AZT2, Q6ES52, Q6NU95, Q7XJS0, Q7ZU45, Q80ZX8, Q91YW3, Q91Z38, Q95L05, Q99614, Q9CYG7, Q9D706

Diamond homologs: A4K2V0, A6HD62, A6ZRW3, D7REX8, F1RBN2, F4IRM4, F4JTI1, F4K487, F4KCL7, O13754, O14217, O16259, O35814, O48802, O54981, O94826, O95801, P07213, P23231, P25638, P31948, P33313, P38825, P53041, P53042, Q07617, Q12118, Q13451, Q15785, Q32PZ3, Q3KRD5, Q3ZBR5, Q43207, Q4R8N7, Q5EA11, Q5PPS5, Q5R8D8, Q5RAP0, Q5U2X2, Q5VJS5

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
FKBP5	down-regulates	NR3C1	binding
FKBP5	“up-regulates activity”	YY1
FKBP5	“up-regulates quantity by expression”	CD274	“catalytic activity”
SRMS	“down-regulates quantity by destabilization”	FKBP5	phosphorylation
MECP2	“down-regulates quantity by repression”	FKBP5	“transcriptional regulation”
FKBP5	up-regulates	Synaptic_plasticity

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 207 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Regulation of RUNX1 Expression and Activity	5	23.5×	5e-05
Transcriptional Regulation by MECP2	9	20.0×	1e-07
Transcriptional Regulation by NPAS4	5	20.0×	9e-05
Regulation of MECP2 expression and activity	7	18.0×	5e-06
HSF1-dependent transactivation	8	17.8×	1e-06
Signaling by RAS mutants	6	17.8×	3e-05
Attenuation phase	6	17.1×	4e-05
MTOR signalling	8	14.9×	4e-06

GO biological processes:

GO term	Partners	Fold	FDR
miRNA-mediated gene silencing by inhibition of translation	5	23.3×	6e-04
stress-activated MAPK cascade	5	18.5×	1e-03
positive regulation of telomere maintenance	5	13.4×	3e-03
protein phosphorylation	35	12.5×	2e-25
regulation of signal transduction by p53 class mediator	5	10.1×	8e-03
protein autophosphorylation	13	9.9×	3e-07
canonical NF-kappaB signal transduction	5	9.6×	9e-03
positive regulation of transcription elongation by RNA polymerase II	6	9.5×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	2
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

2956 predictions. Top by Δscore:

Variant	Effect	Δscore
6:35575939:CTTC:C	acceptor_gain	1.0000
6:35575942:CCTAA:C	acceptor_loss	1.0000
6:35575943:C:CC	acceptor_gain	1.0000
6:35575943:CTAA:C	acceptor_loss	1.0000
6:35575944:T:A	acceptor_loss	1.0000
6:35576991:CA:C	donor_loss	1.0000
6:35576992:A:AG	donor_loss	1.0000
6:35576993:C:A	donor_loss	1.0000
6:35597242:GCTTA:G	donor_loss	1.0000
6:35597243:CTTAC:C	donor_loss	1.0000
6:35597244:TTA:T	donor_loss	1.0000
6:35597245:TACCT:T	donor_loss	1.0000
6:35597246:ACCT:A	donor_loss	1.0000
6:35597247:C:A	donor_loss	1.0000
6:35597278:T:TA	donor_gain	1.0000
6:35597401:TGGA:T	acceptor_gain	1.0000
6:35597402:GGA:G	acceptor_gain	1.0000
6:35597403:GA:G	acceptor_gain	1.0000
6:35597404:AC:A	acceptor_loss	1.0000
6:35597405:C:CC	acceptor_gain	1.0000
6:35597405:CTG:C	acceptor_loss	1.0000
6:35597406:T:G	acceptor_loss	1.0000
6:35619091:CTT:C	donor_loss	1.0000
6:35619092:TTA:T	donor_loss	1.0000
6:35619094:A:AC	donor_gain	1.0000
6:35619094:ACTTT:A	donor_gain	1.0000
6:35619095:C:CT	donor_gain	1.0000
6:35619095:CT:C	donor_gain	1.0000
6:35619095:CTT:C	donor_gain	1.0000
6:35619095:CTTT:C	donor_gain	1.0000

AlphaMissense

3028 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:35577192:C:A	R356S	1.000
6:35577192:C:G	R356S	1.000
6:35577193:C:A	R356M	1.000
6:35577193:C:G	R356T	1.000
6:35577182:C:G	A360P	0.999
6:35577187:C:T	G358D	0.999
6:35577197:A:C	Y355D	0.999
6:35577204:T:A	K352N	0.999
6:35577204:T:G	K352N	0.999
6:35577205:T:A	K352I	0.999
6:35580084:G:C	C326W	0.999
6:35580100:A:G	L321P	0.999
6:35587058:T:A	K272N	0.999
6:35587058:T:G	K272N	0.999
6:35587105:A:G	W257R	0.999
6:35587105:A:T	W257R	0.999
6:35577100:G:T	A387E	0.998
6:35577151:G:T	A370D	0.998
6:35577181:G:T	A360D	0.998
6:35577194:T:C	R356G	0.998
6:35577206:T:G	K352Q	0.998
6:35580042:A:C	C340W	0.998
6:35580043:C:T	C340Y	0.998
6:35580085:C:T	C326Y	0.998
6:35580086:A:G	C326R	0.998
6:35580091:G:T	A324D	0.998
6:35580092:C:G	A324P	0.998
6:35580094:A:G	L323P	0.998
6:35580096:G:C	N322K	0.998
6:35580096:G:T	N322K	0.998

dbSNP variants (sampled 300 via entrez): RS1000006055 (6:35677287 G>A,T), RS1000008493 (6:35722868 G>A), RS1000032321 (6:35670503 G>A), RS1000043343 (6:35605912 C>G,T), RS1000064876 (6:35621361 G>A,T), RS1000074496 (6:35605697 C>T), RS1000097840 (6:35709949 T>TA), RS1000124661 (6:35592719 A>G), RS1000180606 (6:35640742 T>C), RS1000191685 (6:35704600 G>A,T), RS1000215884 (6:35595271 C>T), RS1000216662 (6:35610318 G>A), RS1000230070 (6:35687213 G>A), RS1000235975 (6:35640439 T>C,G), RS1000242040 (6:35700094 A>C)

Disease associations

OMIM: gene MIM:602623 | disease phenotypes:

GenCC curated gene-disease

Mondo (2): post-traumatic stress disorder (MONDO:0005146), asthma (MONDO:0004979)

Orphanet (0):

HPO phenotypes

2 total (3 of 2 shown, HPO-id order):

HPO	Term
HP:0000716	Depression
HP:0010982	Polygenic inheritance
HP:0002099	Asthma

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST004600_127	Eosinophil percentage of white cells	1.000000e-11
GCST004610_18	White blood cell count	1.000000e-11
GCST004617_26	Eosinophil percentage of granulocytes	1.000000e-10
GCST005195_40	Coronary artery disease	5.000000e-08
GCST007856_44	Colorectal cancer or advanced adenoma	4.000000e-08
GCST008362_156	Birth weight	2.000000e-13
GCST008363_50	Offspring birth weight	2.000000e-16
GCST010571_30	Autoimmune thyroid disease	6.000000e-13
GCST012226_472	Waist circumference adjusted for body mass index	7.000000e-09
GCST012227_975	Hip circumference adjusted for BMI	1.000000e-08
GCST90002381_434	Eosinophil count	3.000000e-12
GCST90002382_341	Eosinophil percentage of white cells	2.000000e-16
GCST90002388_91	Lymphocyte count	9.000000e-21
GCST90002389_320	Lymphocyte percentage of white cells	4.000000e-16
GCST90002394_152	Monocyte percentage of white cells	5.000000e-13
GCST90002399_294	Neutrophil percentage of white cells	3.000000e-13
GCST90020024_827	A body shape index	9.000000e-10
GCST90020025_723	Waist-to-hip ratio adjusted for BMI	4.000000e-13
GCST90020027_1145	Waist-hip index	5.000000e-14
GCST90020029_1553	Waist circumference adjusted for body mass index	4.000000e-08
GCST90020029_1554	Waist circumference adjusted for body mass index	1.000000e-11

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0007991	eosinophil percentage of leukocytes
EFO:0007996	eosinophil percentage of granulocytes
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference
EFO:0004842	eosinophil count
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007989	monocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D001249	Asthma	C08.127.108; C08.381.495.108; C08.674.095; C20.543.480.680.095
D013313	Stress Disorders, Post-Traumatic	F03.950.750.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2052031 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 270,603 (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
CHEMBL269732	TACROLIMUS ANHYDROUS	4	95,168
CHEMBL413	SIROLIMUS	4	172,798
CHEMBL350775	BIRICODAR	2	2,637

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

PharmGKB clinical annotations

11 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1360780	Toxicity	3	clomipramine;nefazodone;paroxetine;venlafaxine	Depression
rs1360780	Efficacy	3	clozapine	Schizophrenia
rs1360780	Efficacy	3	antidepressants;citalopram;clomipramine;lithium;nefazodone;paroxetine;venlafaxine	Depression
rs17614642	Efficacy	3	bupropion	Major Depressive Disorder
rs3800373	Efficacy	3	antidepressants	Depression
rs4713916	Efficacy	3	corticosteroids	Crohn Disease
rs4713916	Efficacy	3	antidepressants;Selective serotonin reuptake inhibitors	Depressive Disorder;Mood Disorder
rs4713916	Efficacy	3	fluoxetine	Mood Disorder
rs4713916	Efficacy	3	mirtazapine	Mood Disorder
rs73748206	Other	3	gemcitabine
rs9380524	Efficacy	3	citalopram;escitalopram	Major Depressive Disorder

PharmGKB variants

6 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1360780	FKBP5	3	5.75	3	clomipramine;nefazodone;paroxetine;venlafaxine;antidepressants;citalopram;clomipramine;lithium;nefazodone;paroxetine;venlafaxine;clozapine
rs3800373	FKBP5	3	2.50	1	antidepressants
rs4713916	FKBP5	3	4.25	4	fluoxetine;mirtazapine;corticosteroids;antidepressants;Selective serotonin reuptake inhibitors
rs9380524	FKBP5	3	0.00	1	citalopram;escitalopram
rs73748206	FKBP5	3	0.00	1	gemcitabine
rs17614642	FKBP5	3	2.25	1	bupropion

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Peptidyl-prolyl cis/trans isomerases

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
SAFit1	Inhibitor	8.4	pKi
SAFit2	Inhibitor	8.22	pKi
compound 19b [PMID: 37058391]	Inhibition	7.72	pKi
SLF	Inhibitor	5.2	pIC50

Binding affinities (BindingDB)

5 measured of 6 human assays (6 total across all organisms); most potent 5 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL2348587	KI	1200 nM
CHEMBL2348593	KD	10500 nM
CHEMBL2348596	KI	27000 nM
CHEMBL2348610	KI	51100 nM
CHEMBL2348590	KI	64800 nM

ChEMBL bioactivities

236 potent at pChembl≥5 of 288 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.52	Ki	3	nM	SIROLIMUS
8.43	Kd	3.7	nM	SIROLIMUS
8.40	Ki	4	nM	CHEMBL3623612
8.40	Ki	4	nM	CHEMBL5286207
8.40	Ki	4	nM	CHEMBL5414438
8.30	Kd	5	nM	CHEMBL4871144
8.30	Ki	5	nM	CHEMBL5419523
8.22	Ki	6	nM	CHEMBL3623630
8.22	Kd	6	nM	CHEMBL3623630
8.22	Ki	6	nM	CHEMBL5281156
8.22	Ki	6	nM	CHEMBL3623612
8.17	Kd	6.7	nM	CHEMBL5634031
8.16	Kd	6.9	nM	CHEMBL4871144
8.15	Ki	7	nM	CHEMBL5399488
8.15	Ki	7	nM	CHEMBL5399071
8.10	Kd	8	nM	CHEMBL4858532
8.10	Ki	8	nM	CHEMBL5420939
8.07	Kd	8.5	nM	SIROLIMUS
8.01	Kd	9.8	nM	CHEMBL3623612
7.96	Kd	11	nM	CHEMBL4878890
7.92	Kd	12	nM	CHEMBL4856956
7.92	Kd	12	nM	CHEMBL4863989
7.89	Ki	13	nM	CHEMBL5397271
7.77	Kd	17	nM	CHEMBL4878667
7.77	Ki	17	nM	CHEMBL5396982
7.72	Ki	19	nM	CHEMBL5437245
7.64	Ki	23	nM	CHEMBL5289205
7.64	Ki	23	nM	CHEMBL5408325
7.61	Ki	24.5	nM	CHEMBL4090599
7.58	Ki	26	nM	CHEMBL5291024
7.55	Kd	28	nM	CHEMBL4876415
7.55	Kd	28	nM	CHEMBL4866742
7.54	Kd	29	nM	CHEMBL4872580
7.39	Ki	41	nM	CHEMBL5405460
7.37	Ki	43	nM	CHEMBL3792975
7.34	Kd	46	nM	CHEMBL4870008
7.27	Kd	53.27	nM	CHEMBL5653589
7.27	ED50	53.27	nM	CHEMBL5653589
7.26	Kd	55	nM	CHEMBL4859741
7.26	Kd	55	nM	CHEMBL5746298
7.26	Kd	55	nM	CHEMBL5757176
7.26	Kd	55	nM	CHEMBL6019025
7.26	Kd	55	nM	CHEMBL5853506
7.26	Kd	55	nM	CHEMBL5967081
7.26	Kd	55	nM	CHEMBL5994641
7.26	Kd	55	nM	CHEMBL5853787
7.26	Kd	55	nM	CHEMBL5897947
7.26	Kd	55	nM	CHEMBL5866833
7.26	Kd	55	nM	CHEMBL5898116
7.26	Kd	55	nM	CHEMBL5984129

PubChem BioAssay actives

187 with measured affinity, of 302 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
Sirolimus	740342: Binding affinity to human FKBP51 by competitive fluorescence polarization assay	ki	0.0030	uM
2-[3-[(1R)-1-[(2S)-1-[(2S)-2-(5-chlorothiophen-2-yl)-2-(3,4,5-trimethoxyphenyl)acetyl]piperidine-2-carbonyl]oxy-3-(3,4-dimethoxyphenyl)propyl]phenoxy]acetic acid	1987846: Binding affinity to FKBP51 (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	0.0040	uM
2-[3-[(1R)-1-[(2S)-1-[(2R)-3-cyclohexyl-2-(3,4,5-trimethoxyphenyl)propanoyl]piperidine-2-carbonyl]oxy-3-(3,4-dimethoxyphenyl)propyl]phenoxy]acetic acid	1949536: Binding affinity to wild type FKBP51 (unknown origin) by competitive fluorescence polarization assay	ki	0.0040	uM
2-[3-[(1R)-1-[(2S)-1-[(2S)-2-cyclohexyl-2-(3,4,5-trimethoxyphenyl)acetyl]piperidine-2-carbonyl]oxy-3-(3,4-dimethoxyphenyl)propyl]phenoxy]acetic acid	1251956: Displacement of iFit-FL from FKBP51 (unknown origin) by fluorescence polarization assay	ki	0.0040	uM
(2S,9S,12R,20R,21R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-20,21-dihydroxy-25,26-dimethoxy-11,18,23-trioxa-4-azatetracyclo[22.3.1.113,17.04,9]nonacosa-1(28),13(29),14,16,24,26-hexaene-3,10-dione	1775630: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP51 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition binding assay	kd	0.0050	uM
(2S,9S,12R,20R,21S)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-20,21-dihydroxy-25,26-dimethoxy-11,18,23-trioxa-4-azatetracyclo[22.3.1.113,17.04,9]nonacosa-1(28),13(29),14,16,24,26-hexaene-3,10-dione	1987844: Binding affinity to FKBP51 (unknown origin)	ki	0.0050	uM
[(1R)-3-(3,4-dimethoxyphenyl)-1-[3-(2-morpholin-4-ylethoxy)phenyl]propyl] (2S)-1-[(2R)-3-cyclohexyl-2-(3,4,5-trimethoxyphenyl)propanoyl]piperidine-2-carboxylate	1949536: Binding affinity to wild type FKBP51 (unknown origin) by competitive fluorescence polarization assay	ki	0.0060	uM
[(1R)-3-(3,4-dimethoxyphenyl)-1-[3-(2-morpholin-4-ylethoxy)phenyl]propyl] (2S)-1-[(2S)-2-cyclohexyl-2-(3,4,5-trimethoxyphenyl)acetyl]piperidine-2-carboxylate	1251956: Displacement of iFit-FL from FKBP51 (unknown origin) by fluorescence polarization assay	ki	0.0060	uM
(1R,9S,12S,15S,16E,20E,23R,24S,27R)-1-hydroxy-15,23,27-trimethyl-12-[(2R)-1-[(1S,2S,3S,4R)-2,3,4-trihydroxycyclohexyl]propan-2-yl]-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacosa-16,20-diene-2,3,10,22-tetrone	2139769: Binding affinity to human FKBP51 FK1 domain expressed in Escherichia coli BL21 DE3 Gold assessed as dissociation constant incubated for 30 mins by competitive fluorescence polarization assay	kd	0.0067	uM
2-[3-[(1R)-3-(3,4-dimethoxyphenyl)-1-[(2S)-1-[(2S)-2-(5-methylthiophen-2-yl)-2-(3,4,5-trimethoxyphenyl)acetyl]piperidine-2-carbonyl]oxypropyl]phenoxy]acetic acid	1987846: Binding affinity to FKBP51 (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	0.0070	uM
2-[3-[(1R)-1-[(2S)-1-[(2S)-2-(5-bromothiophen-2-yl)-2-(3,4,5-trimethoxyphenyl)acetyl]piperidine-2-carbonyl]oxy-3-(3,4-dimethoxyphenyl)propyl]phenoxy]acetic acid	1987846: Binding affinity to FKBP51 (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	0.0070	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-26,27-dimethoxy-11,18,24-trioxa-4-azatetracyclo[23.3.1.113,17.04,9]triaconta-1(29),13(30),14,16,25,27-hexaene-3,10,21-trione	1775630: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP51 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition binding assay	kd	0.0080	uM
2-[3-[(1R)-3-(3,4-dimethoxyphenyl)-1-[(2S)-1-[(2R)-3-morpholin-4-yl-2-(3,4,5-trimethoxyphenyl)propanoyl]piperidine-2-carbonyl]oxypropyl]phenoxy]acetic acid	1987846: Binding affinity to FKBP51 (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	0.0080	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-25,28-dimethoxy-11,18,23-trioxa-4-azatetracyclo[22.2.2.113,17.04,9]nonacosa-1(26),13(29),14,16,24,27-hexaene-3,10,20-trione	1775630: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP51 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition binding assay	kd	0.0110	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-20,21-dihydroxy-25,28-dimethoxy-11,18,23-trioxa-4-azatetracyclo[22.2.2.113,17.04,9]nonacosa-1(26),13(29),14,16,24,27-hexaene-3,10-dione	1775630: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP51 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition binding assay	kd	0.0120	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-25,26-dimethoxy-11,18,23-trioxa-4-azatetracyclo[22.3.1.113,17.04,9]nonacosa-1(28),13(29),14,16,24,26-hexaene-3,10,20-trione	1775630: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP51 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition binding assay	kd	0.0120	uM
2-[3-[(1R)-3-(3,4-dimethoxyphenyl)-1-[(2S)-1-[(2S)-2-(5-ethylthiophen-2-yl)-2-(3,4,5-trimethoxyphenyl)acetyl]piperidine-2-carbonyl]oxypropyl]phenoxy]acetic acid	1987846: Binding affinity to FKBP51 (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	0.0130	uM
(2S,9S,12R,20S,21S)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-20,21-dihydroxy-25,26-dimethoxy-11,18,23-trioxa-4-azatetracyclo[22.3.1.113,17.04,9]nonacosa-1(28),13(29),14,16,24,26-hexaene-3,10-dione	1775630: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP51 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition binding assay	kd	0.0170	uM
[(1R)-3-(3,4-dimethoxyphenyl)-1-[3-(2-morpholin-4-ylethoxy)phenyl]propyl] (2S)-1-[(2S)-2-(5-methylthiophen-2-yl)-2-(3,4,5-trimethoxyphenyl)acetyl]piperidine-2-carboxylate	1987846: Binding affinity to FKBP51 (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	0.0170	uM
[(1R)-3-(3,4-dimethoxyphenyl)-1-[3-(2-morpholin-4-ylethoxy)phenyl]propyl] (2S)-1-[(2S)-2-(5-chlorothiophen-2-yl)-2-(3,4,5-trimethoxyphenyl)acetyl]piperidine-2-carboxylate	1987846: Binding affinity to FKBP51 (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	0.0190	uM
2-[3-[(1R)-1-[(2S)-1-[(2R)-3-cyclohex-2-en-1-yl-2-(3,4,5-trimethoxyphenyl)propanoyl]piperidine-2-carbonyl]oxy-3-(3,4-dimethoxyphenyl)propyl]phenoxy]acetic acid	1949536: Binding affinity to wild type FKBP51 (unknown origin) by competitive fluorescence polarization assay	ki	0.0230	uM
2-[3-[(1R)-1-[(2S)-1-[(2S)-2-(5-cyanothiophen-2-yl)-2-(3,4,5-trimethoxyphenyl)acetyl]piperidine-2-carbonyl]oxy-3-(3,4-dimethoxyphenyl)propyl]phenoxy]acetic acid	1987846: Binding affinity to FKBP51 (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	0.0230	uM
(1S,5S,6R)-10-(3,5-dichlorophenyl)sulfonyl-5-(methoxymethyl)-3-(pyridin-2-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-2-one	1479803: Displacement of 5-(3-(4-(((5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-5-vinyl-3,10-diazabicyclo[4.3.1]decan-3-yl)methyl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3,10-dihydroanthracen-9-yl)benzoate from human FKBP51 after 30 mins by fluorescence polarization assay	ki	0.0245	uM
[(1R)-3-(3,4-dimethoxyphenyl)-1-[3-(2-morpholin-4-ylethoxy)phenyl]propyl] (2S)-1-[(2R)-3-cyclohex-2-en-1-yl-2-(3,4,5-trimethoxyphenyl)propanoyl]piperidine-2-carboxylate	1949536: Binding affinity to wild type FKBP51 (unknown origin) by competitive fluorescence polarization assay	ki	0.0260	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-28,29-dimethoxy-11,18,23,26-tetraoxa-4-azatetracyclo[25.3.1.113,17.04,9]dotriaconta-1(31),13(32),14,16,27,29-hexaene-3,10,21-trione	1775630: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP51 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition binding assay	kd	0.0280	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-26,27-dimethoxy-11,18,24-trioxa-4-azatetracyclo[23.3.1.113,17.04,9]triaconta-1(29),13(30),14,16,25,27-hexaene-3,10,20-trione	1775630: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP51 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition binding assay	kd	0.0280	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-25,26-dimethoxy-11,18,23-trioxa-4-azatetracyclo[22.3.1.113,17.04,9]nonacosa-1(28),13(29),14,16,24,26-hexaene-3,10-dione	1775630: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP51 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition binding assay	kd	0.0290	uM
2-[3-[(1R)-1-[(2S)-1-[(2S)-2-(5-cyclopropylthiophen-2-yl)-2-(3,4,5-trimethoxyphenyl)acetyl]piperidine-2-carbonyl]oxy-3-(3,4-dimethoxyphenyl)propyl]phenoxy]acetic acid	1987846: Binding affinity to FKBP51 (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	0.0410	uM
2-[3-[(1R)-1-[[(2S)-1-[(2S)-2-cyclohexyl-2-(3,4,5-trimethoxyphenyl)acetyl]piperidine-2-carbonyl]amino]-3-(3,4-dimethoxyphenyl)propyl]phenoxy]acetic acid	1293678: Binding affinity to FKBP51 FK506-binding domain (1 to 140 amino acids) (unknown origin) incubated for 30 mins using fluorescein-conjugated 2-(5-((2-(3-((R)-3-(3,4-dimethoxyphenyl)-1-((S)-1-(3,3-dimethyl-2-oxopentanoyl)piperidine-2-carbonyloxy)propyl)phenoxy)acetamido)methyl)-6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid by competitive fluorescence polarization assay	ki	0.0430	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-26,27-dimethoxy-11,18,24-trioxa-4-azatetracyclo[23.3.1.113,17.04,9]triaconta-1(29),13(30),14,16,25,27-hexaene-3,10-dione	1775630: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP51 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition binding assay	kd	0.0460	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148391: Binding affinity to human FKBP5 incubated for 45 mins by Kinobead based pull down assay	kd	0.0533	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-23,24-dimethoxy-11,18,21-trioxa-4-azatetracyclo[20.3.1.113,17.04,9]heptacosa-1(26),13(27),14,16,22,24-hexaene-3,10-dione	1775630: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP51 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition binding assay	kd	0.0550	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-28,29-dimethoxy-11,18,23,26-tetraoxa-4-azatetracyclo[25.3.1.113,17.04,9]dotriaconta-1(31),13(32),14,16,27,29-hexaene-3,10-dione	1775630: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP51 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition binding assay	kd	0.0610	uM
(2S,9S,12R,20E)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-28,29-dimethoxy-11,18,23,26-tetraoxa-4-azatetracyclo[25.3.1.113,17.04,9]dotriaconta-1(31),13(32),14,16,20,27,29-heptaene-3,10-dione	1775630: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP51 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition binding assay	kd	0.0620	uM
(2S,9S,12R,20Z)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-25,28-dimethoxy-11,18,23-trioxa-4-azatetracyclo[22.2.2.113,17.04,9]nonacosa-1(26),13(29),14,16,20,24,27-heptaene-3,10-dione	1775630: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP51 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition binding assay	kd	0.0670	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-23,26-dimethoxy-11,18,21-trioxa-4-azatetracyclo[20.2.2.113,17.04,9]heptacosa-1(24),13(27),14,16,22,25-hexaene-3,10-dione	1775630: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP51 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition binding assay	kd	0.0680	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-24,27-dimethoxy-11,18,22-trioxa-4-azatetracyclo[21.2.2.113,17.04,9]octacosa-1(25),13(28),14,16,23,26-hexaene-3,10-dione	1775630: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP51 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition binding assay	kd	0.0700	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-24,25-dimethoxy-11,18,22-trioxa-4-azatetracyclo[21.3.1.113,17.04,9]octacosa-1(27),13(28),14,16,23,25-hexaene-3,10-dione	1775630: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP51 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition binding assay	kd	0.0700	uM
(2S,9S,12R,20Z)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-26,27-dimethoxy-11,18,24-trioxa-4-azatetracyclo[23.3.1.113,17.04,9]triaconta-1(29),13(30),14,16,20,25,27-heptaene-3,10-dione	1775630: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP51 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition binding assay	kd	0.0710	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-29,32-dimethoxy-11,18,23,27-tetraoxa-4-azatetracyclo[26.2.2.113,17.04,9]tritriaconta-1(30),13(33),14,16,28,31-hexaene-3,10-dione	1775630: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP51 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition binding assay	kd	0.0750	uM
Tacrolimus	2139769: Binding affinity to human FKBP51 FK1 domain expressed in Escherichia coli BL21 DE3 Gold assessed as dissociation constant incubated for 30 mins by competitive fluorescence polarization assay	kd	0.0759	uM
[(1R)-3-(3,4-dimethoxyphenyl)-1-(3-methoxyphenyl)propyl] (2S)-1-[(2S)-2-cyclohexyl-2-(3,4,5-trimethoxyphenyl)acetyl]piperidine-2-carboxylate	1775630: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP51 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition binding assay	kd	0.0830	uM
(2S,9S,12R,20E)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-29,32-dimethoxy-11,18,23,27-tetraoxa-4-azatetracyclo[26.2.2.113,17.04,9]tritriaconta-1(30),13(33),14,16,20,28,31-heptaene-3,10-dione	1775630: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP51 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition binding assay	kd	0.0840	uM
(2S,9S,12R,20Z)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-26,29-dimethoxy-11,18,24-trioxa-4-azatetracyclo[23.2.2.113,17.04,9]triaconta-1(27),13(30),14,16,20,25,28-heptaene-3,10-dione	1775630: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP51 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition binding assay	kd	0.0880	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-25,28-dimethoxy-11,18,23-trioxa-4-azatetracyclo[22.2.2.113,17.04,9]nonacosa-1(26),13(29),14,16,24,27-hexaene-3,10-dione	1775630: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP51 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition binding assay	kd	0.0890	uM
(2S,9S,12R,20E)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-25,28-dimethoxy-11,18,23-trioxa-4-azatetracyclo[22.2.2.113,17.04,9]nonacosa-1(26),13(29),14,16,20,24,27-heptaene-3,10-dione	1775630: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP51 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition binding assay	kd	0.0890	uM
3,5-dibenzamido-N-(3,4-dimethylphenyl)benzamide	2084021: Inhibition of GST-tagged human FKBP51 expressed in Escherichia coli BL21 (DE3) using NH2-EDASRMEEVD-COOH peptide as substrate preincubated for 15 mins followed by substrate addition measured after 15 mins by Alpha Screen assay	ic50	0.1000	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-29,30-dimethoxy-11,18,23,27-tetraoxa-4-azatetracyclo[26.3.1.113,17.04,9]tritriaconta-1(32),13(33),14,16,28,30-hexaene-3,10-dione	1775630: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP51 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition binding assay	kd	0.1030	uM
2-[3-[(1R)-3-(3,4-dimethoxyphenyl)-1-[(2S)-1-[(2S)-2-thiophen-2-yl-2-(3,4,5-trimethoxyphenyl)acetyl]piperidine-2-carbonyl]oxypropyl]phenoxy]acetic acid	1987846: Binding affinity to FKBP51 (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	0.1030	uM
(2S,9S,12R,20Z)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-28,31-dimethoxy-11,18,23,26-tetraoxa-4-azatetracyclo[25.2.2.113,17.04,9]dotriaconta-1(29),13(32),14,16,20,27,30-heptaene-3,10-dione	1775630: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP51 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition binding assay	kd	0.1060	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Dexamethasone	decreases reaction, increases expression, increases reaction, affects cotreatment, decreases expression (+1 more)	9
Progesterone	decreases reaction, increases expression, affects cotreatment	6
sodium arsenite	affects cotreatment, affects expression, decreases expression, increases expression	5
Estradiol	decreases reaction, affects cotreatment, increases expression	5
bisphenol A	decreases expression, increases expression	4
Metribolone	decreases reaction, increases expression	4
Dihydrotestosterone	increases expression	3
Tretinoin	decreases expression	3
Cadmium Chloride	decreases expression	3
mercuric bromide	decreases expression, affects cotreatment	2
perfluorooctane sulfonic acid	decreases expression	2
entinostat	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	2
bisphenol S	increases expression, affects cotreatment, decreases expression	2
Arsenic Trioxide	affects expression, affects binding, decreases reaction	2
Air Pollutants	decreases expression, increases abundance	2
Doxorubicin	increases degradation, decreases expression, affects reaction	2
Lipopolysaccharides	decreases expression, decreases reaction, increases expression, affects response to substance	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	decreases expression, decreases methylation	2
Valproic Acid	affects expression, increases expression	2
Cyclosporine	decreases expression, affects cotreatment	2
Medroxyprogesterone Acetate	increases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment	2
NVP-BHG712	affects cotreatment, decreases expression, increases reaction	1
FR900359	increases phosphorylation	1
darolutamide	decreases expression, decreases reaction	1
bisphenol F	increases expression	1
testosterone enanthate	affects expression	1
quinomethionate	affects expression	1

ChEMBL screening assays

38 unique, capped per target: 38 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2061147	Binding	Binding affinity to FKBP51 FK1 domain by competitive fluorescence polarization assay	Exploration of pipecolate sulfonamides as binders of the FK506-binding proteins 51 and 52. — J Med Chem

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B7XA	Abcam Raji FKBP5 KO	Cancer cell line	Male
CVCL_B9XZ	Abcam THP-1 FKBP5 KO	Cancer cell line	Male
CVCL_C6ZT	Abcam PC-3 FKBP5 KO	Cancer cell line	Male
CVCL_D7PX	Ubigene A-549 FKBP5 KO	Cancer cell line	Male
CVCL_SN62	HAP1 FKBP5 (-) 1	Cancer cell line	Male
CVCL_XN79	HAP1 FKBP5 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00006489	PHASE4	COMPLETED	Treatment for Alcoholism and Post-Traumatic Stress Disorder (Naltrexone)
NCT00025740	PHASE4	COMPLETED	Clonazepam and Paroxetine for Rapid Treatment of Post-Traumatic Stress Disorder
NCT00050804	PHASE4	COMPLETED	Evaluation of Stress Disorders
NCT00120250	PHASE4	COMPLETED	Eszopiclone for Sleep Disturbance and Nightmares in Post-Traumatic Stress Disorder
NCT00134446	PHASE4	UNKNOWN	Transcranial Magnetic Stimulation for Post-Traumatic Stress Disorder
NCT00158262	PHASE4	COMPLETED	Effect of Propranolol on Preventing Posttraumatic Stress Disorder
NCT00203385	PHASE4	TERMINATED	Maintenance Phase Treatment With Divalproex for Post Traumatic Stress Disorder
NCT00203463	PHASE4	COMPLETED	Topiramate in the Treatment of Post Traumatic Stress Disorder (PTSD)
NCT00204737	PHASE4	COMPLETED	Short Course Glucocorticoid Treatment for PTSD
NCT00208130	PHASE4	COMPLETED	Topiramate in the Treatment of Posttraumatic Stress Disorder in Civilians
NCT00208182	PHASE4	COMPLETED	Risperidone in the Treatment of PTSD in Women Survivors of Domestic Abuse and Rape Trauma
NCT00208208	PHASE4	COMPLETED	Geodon (Ziprasidone) for Posttraumatic Stress Disorder
NCT00237393	PHASE4	COMPLETED	Quetiapine Treatment for Post-Traumatic Stress Disorder (PTSD)
NCT00302107	PHASE4	COMPLETED	A Placebo-Controlled Study of Mirtazapine for PTSD
NCT00330239	PHASE4	COMPLETED	Paroxetine Treatment in Outpatients With Comorbid PTSD and Substance Dependence
NCT00347269	PHASE4	COMPLETED	Primary Care Intervention Strategy for Anxiety Disorders
NCT00352469	PHASE4	COMPLETED	Trial of Seroquel SR for Alcohol Dependence and Comorbid Anxiety
NCT00391430	PHASE4	TERMINATED	Cognitive Behavioral Therapy Versus Sertraline in the Treatment of Post-Traumatic Stress Disorder
NCT00648375	PHASE4	TERMINATED	Effectiveness of Propranolol For Treating People With Post-Traumatic Stress Disorder
NCT00700999	PHASE4	COMPLETED	Brain Markers of Treatment Response in Post-Traumatic Stress Disorder (PTSD)
NCT00706173	PHASE4	WITHDRAWN	Trial of Hydrocortisone for Post-Traumatic Stress Disorder (PTSD)
NCT00917397	PHASE4	COMPLETED	The Outcome of Treatment of Traumatised Refugees With Psychotherapy and/or Antidepressants
NCT01087736	PHASE4	COMPLETED	Topiramate Treatment of Alcohol Use Disorders in Veterans With Post Traumatic Stress Disorder (PTSD): A Pilot Controlled Trial of Augmentation Therapy
NCT01271244	PHASE4	COMPLETED	Effects of Escitalopram on Autonomic Reactivity in Post Traumatic Stress Disorder
NCT01325168	PHASE4	COMPLETED	The Effect of Intranasal Oxytocin on Emphatic Abilities in Patients With Post Traumatic Stress Disorder (PTSD)
NCT01490697	PHASE4	COMPLETED	Developing Memory Reconsolidation Blockers as Novel Posttraumatic Stress Disorder (PTSD) Treatments
NCT01517711	PHASE4	COMPLETED	Tramadol Extended-Release (ER) for Posttraumatic Stress Disorder (PTSD)
NCT01569685	PHASE4	COMPLETED	The Treatment of Traumatised Refugees With Sertraline Versus Venlafaxine in Combination With Psychotherapy
NCT01681849	PHASE4	COMPLETED	Neural Circuits in Women With Abuse and Posttraumatic Stress Disorder
NCT01715519	PHASE4	COMPLETED	Vilazodone for the Treatment of Posttraumatic Stress Disorder
NCT01965366	PHASE4	COMPLETED	Dexamethasone Plus Virtual Reality Exposure Therapy for PTSD
NCT02199652	PHASE4	COMPLETED	Reducing Suicidal Ideation Through Treatment of Nightmares-Post Traumatic Stress Disorder (PTSD)
NCT02213900	PHASE4	COMPLETED	Preventing Post-Operative Delirium in Patients Undergoing a Pneumonectomy, Esophagectomy or Thoracotomy
NCT02258828	PHASE4	COMPLETED	An Open-Label Trial of Memantine for Cognitive Impairment in Patients With Post-Traumatic Stress Disorder
NCT02287038	PHASE4	COMPLETED	Atomoxetine in Veterans With Comorbid ADHD/PTSD
NCT02336568	PHASE4	UNKNOWN	The Effect of 21-Days Intranasal Oxytocin on Patients With Post Traumatic Stress Disorder (PTSD)
NCT02504931	PHASE4	COMPLETED	Serotonin Selective Reuptake Inhibitor Treatment of Dual Diagnosis Post-traumatic Stress Disorder and Alcohol Problems
NCT02520726	PHASE4	TERMINATED	PTSD Prevention Study Examining the Efficacy of Sertraline in Burn Victims
NCT02637895	PHASE4	COMPLETED	Vortioxetine for Posttraumatic Stress Disorder
NCT02761161	PHASE4	COMPLETED	Treatment of Sleep Disturbances in Trauma-affected Refugees