FKBP5

FKBP prolyl isomerase 5

Score: 0.586 Price: $0.59 Medium Druggability Status: active Wiki: FKBP5

🧠 Neurodegeneration

HYPOTHESES

4

PAPERS

14

KG EDGES

206

DEBATES

1

3D Protein Structure

🧬 FKBP5 — PDB 1KT0 Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Medium

Score: 0.47

Clinical Stage

Phase I

Target Class

Enzyme

Safety

0.60

Druggability Analysis

Drug Development0.15

Structural Tractability0.95

Target Class0.85

Safety Profile0.60

Key Metrics

PDB Structures:

135

Known Drugs:

2

Approved:

0

In Clinical Trials:

0

Drug Pipeline (2 compounds)

2 Preclinical

Druggability Rationale: FKBP5 presents medium druggability (0.60) supported by its well-defined enzyme active site, extensive structural characterization (135 PDB structures at 0.85 Å resolution), and two preclinical inhibitors (SAFit2, iFit1) demonstrating target tractability. However, medium scoring reflects challenges in achieving potency and selectivity within the FKBP family, and the prolyl isomerase mechanism requires optimization for pharmacokinetic properties and CNS penetration for neuropsychiatric indications.

Mechanism: Small molecule inhibitor of prolyl isomerase activity and HSP90 co-chaperone function

Drug Pipeline (2 compounds)

2 Preclinical

Known Drugs:

SAFit2 (preclinical) — stress-related disorders

iFit1 (preclinical) — depression

Structural Data:

PDB (135) ✓AlphaFold ✓Cryo-EM ✓

1KT0 3O5D 3O5E 3O5F 3O5G+130 more

UniProt: Q13451

🧬 3D Protein Structure

🧬 FKBP5 — PDB 1KT0 Click to expand interactive 3D viewer

Experimental structure from RCSB PDB | Powered by Mol* | Rotate: click+drag | Zoom: scroll

Selectivity & Safety Considerations

FKBP5 selectivity is a significant challenge due to high sequence homology with other FKBP family members (FKBP1A, FKBP1B, FKBP4); achieving selectivity while avoiding off-target immunophilin activity is critical. Co-chaperone function selectivity versus prolyl isomerase inhibition must be carefully validated to minimize unintended HSP90 pathway modulation.

3D Protein Structure

PDB: Open in RCSB AlphaFold model

Interactive 3D viewer powered by RCSB PDB / Mol*. Use mouse to rotate, scroll to zoom.

Clinical Trials (10)

Relevant trials from ClinicalTrials.gov

Active

3

Completed

4

Total Enrollment

1,804

By Phase

NA: 4 · PHASE1: 1 · Unknown: 5

Adverse Childhood Experiences, Adaptation and Breast Cancer Completed

Unknown NCT05843539 n=100

Adverse Childhood Experiences, Cancer, Breast, Attachment Styles

Interventions: Biological and epigenetic measures

Sponsor: University of Lorraine | Started: 2022-04-12

Identification of Pathways to Mitigate Immune-Related Adverse Events With Cancer Immunotherapy Unknown

Unknown NCT04283539 n=238

Cancer

Interventions: systemic corticosteroid or biologic

Sponsor: National Jewish Health | Started: 2020-06-01

Measuring Outcomes of Maternal COVID-19-related Prenatal Exposure Completed

Unknown NCT04540029 n=350

Prenatal Stress

Interventions: Maternal stress

Sponsor: IRCCS National Neurological Institute "C. Mondino" Foundatio | Started: 2020-05-06

Clinical Implications of FKBP5 in Stroke Unknown

NA NCT05198037 n=500

Stroke

Interventions: Bihemispheric tDCS

Sponsor: Taipei Veterans General Hospital, Taiwan | Started: 2021-11-01

Biomarker Expression in Patients With ACTH-Dependent Cushing's Syndrome Before and After Surgery Completed

Unknown NCT02922257 n=26

Cushing's Syndrome

Sponsor: Corcept Therapeutics | Started: 2016-11

Maternal Mental Health Trial Recruiting

PHASE1 NCT04685148 n=220

Major Depressive Disorder, Postpartum Depression

Interventions: Transdermal patch estradiol, Transdermal patch placebo

Sponsor: Vibe G Frøkjær, MD, PhD | Started: 2021-02-03

The Application of Virtual Reality Exposure Versus Relaxation Training in Music Performance Anxiety Unknown

NA NCT05735860 n=46

Music Performance Anxiety

Interventions: Virtual Reality Exposure Therapy (VRET), Progressive Muscle Relaxation (PMR)

Sponsor: Wuerzburg University Hospital | Started: 2022-01-11

Fertility And Sexual Function In CAH: CALLIOPE Recruiting

Unknown NCT07099456 n=50

Congenital Adrenal Hyperplasia (CAH)

Sponsor: University of Roma La Sapienza | Started: 2024-11-01

Linked Hypotheses (1)

Competitive Co-chaperone Displacement0.455

Linked Experiments (0)

No linked experiments

Scoring Dimensions

Knowledge Graph (20)

activates (1)

associated with (3)

FKBP5→neurodegenerationFKBP5→JUNFKBP5→TNF

co discussed (6)

APOE→FKBP5HSPA1A→FKBP5DNAJB1→FKBP5HSP90AA1→FKBP5ST6GAL1→FKBP5

▸ Show 1 more

interacts with (10)

HSPA1A→FKBP5HSP90AA1→FKBP5DNAJB1→FKBP5FKBP5→HSPA1AFKBP5→HSP90AA1

▸ Show 5 more

FKBP5→DNAJB1FKBP4→FKBP5CRH→FKBP5FKBP5→CRHR1FKBP5→NR3C1

Debate History (1)

Should FKBP5 (FKBP prolyl isomerase 5) be prioritized as a therapeutic target fo2026-04-21