NAMPT

Nicotinamide phosphoribosyltransferase

Score: 0.543 Price: $0.54 Low Druggability Status: active Wiki: NAMPT

🧠 Neurodegeneration

HYPOTHESES

3

PAPERS

22

KG EDGES

235

DEBATES

1

3D Protein Structure

🧬 NAMPT — PDB 2GVJ Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.45

Clinical Stage

Phase II

Target Class

Enzyme

Safety

0.40

Druggability Analysis

Drug Development0.30

Structural Tractability0.95

Target Class0.85

Safety Profile0.40

Key Metrics

PDB Structures:

85

Known Drugs:

2

Approved:

0

In Clinical Trials:

0

Drug Pipeline (2 compounds)

Druggability Rationale: NAMPT is highly druggable (0.80 score) due to its well-defined active site, abundant structural data (85 PDB structures at 1.32 Å resolution), and established precedent with clinical candidates FK866 and CHS-828. However, clinical translation has been challenged by toxicity and selectivity issues rather than target validation, suggesting the enzyme itself is tractable but requires optimization of inhibitor properties.

Mechanism: Small molecule competitive inhibitors of NAD+ biosynthesis enzyme

Drug Pipeline (2 compounds)

Known Drugs:

FK866 (failed_phase_2) — cancer

CHS-828 (failed_phase_2) — cancer

Structural Data:

PDB (85) ✓AlphaFold ✓Cryo-EM —

2GVG 2GVJ 2GVL 2H3B 2H3D+80 more

UniProt: A0A7P0TA73

🧬 3D Protein Structure

🧬 NAMPT — PDB 2GVJ Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

NAMPT selectivity is favorable as the enzyme has limited isoforms (primarily intracellular form), but off-target liabilities to other NAD+-consuming enzymes (PARPs, sirtuins) and broad NAD+ depletion effects present selectivity challenges. Tissue-specific NAD+ dependence may cause collateral damage in energy-demanding tissues (neurons, muscle), limiting therapeutic windows.

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 (8)

Relevant trials from ClinicalTrials.gov

Active

1

Completed

7

Total Enrollment

860

By Phase

NA: 5 · PHASE1: 1 · PHASE2: 1 · Unknown: 1

Anger Control Training for Youth With Tourette Syndrome Completed

NA NCT00486551 n=26

Tourette Syndrome, Chronic Tic Disorder, Oppositional Defiant Disorder

Interventions: Anger control training

Sponsor: Yale University | Started: 2001-08

Adaptive vs. Continuous Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease Recruiting

NA NCT06909045 n=130

Deep Brain Stimulation, Parkinson Disease

Interventions: Adaptive DBS, Continue DBS

Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC | Started: 2026-01-27

Expiratory Muscle Training in Patients With Parkinson's Disease Completed

PHASE1 NCT00843739 n=90

Parkinson's Disease

Interventions: EMST - Active Treatment, sham EMST

Sponsor: University of Florida | Started: 2004-01

Study of the Follow-up of Stroke Treated With Anticoagulants Completed

Unknown NCT03292575 n=441

Stroke

Interventions: Anticoagulants

Sponsor: Centre Hospitalier Universitaire Dijon | Started: 2016-01

Early Detection and Prevention of Mild Cognitive Impairment Due to Cerebrovascular Disease Completed

NA NCT01924312 n=80

Cerebrovascular Disease, Mild Cognitive Impairment

Interventions: Heart Health Intervention

Sponsor: Gregory Jicha, 323-5550 | Started: 2013-05

Effects of Modern Board Games on Well Being in Older Adults Completed

NA NCT06306365 n=35

Executive Functions

Interventions: Modern board game-based learning

Sponsor: European University Miguel de Cervantes | Started: 2024-02-07

Treatment of Alzheimer's and Dementia With the Metabolism, Infections, Nutrition, Drug Elimination (MIND) Protocol Completed

NA NCT02260167 n=25

Alzheimer's Disease, Dementia

Interventions: A mix of natural treatments and medicati

Sponsor: Practitioners Alliance Network | Started: 2014-09

A Phase 2 Study to Evaluate Safety of Long-term AL001 Dosing in Frontotemporal Dementia (FTD) Patients (INFRONT-2) Completed

PHASE2 NCT03987295 n=33

Frontotemporal Dementia

Interventions: AL001

Sponsor: Alector Inc. | Started: 2019-09-27

Linked Hypotheses (3)

TREM2 R47H Variant-Driven Metabolic Dysfunction as the Primary Trigger for Failed DAM Transition0.862

Metabolic NAD+ Salvage Pathway Enhancement Through NAMPT Overexpression0.745

NAD+ Salvage Pathway Optimization0.455

Linked Experiments (5)

FK866 efficacy in IBD patient-derived lamina propria cells0.950

FK866 treatment in DSS-induced colitis mouse model0.900

NAD depletion effects on monocyte/macrophage differentiation0.900

FK866 in azoxymethane/DSS colitis-associated cancer model0.850

FK866 mechanism validation in Rag1-/- mice0.850

Scoring Dimensions

Knowledge Graph (20)

co discussed (13)

MMP9→NAMPTSLC7A11→NAMPTAQP4→NAMPTC1Q→NAMPTNAMPT→GPX4

▸ Show 8 more

NAMPT→PLA2G6NAMPT→MMP2NAMPT→C3NAMPT→PLA2G4ACGAS→NAMPTNAMPT→IL1BNAMPT→DNASE2NAMPT→STING1

inhibits (2)

NAMPT→SIRT6NAMPT→EGR2

interacts with (3)

CD38→NAMPTNAMPT→CD38NAMPT→TLR4

regulates (2)

CD38→NAMPTNAMPT→SIRT1

Debate History (1)

Should NAMPT (Nicotinamide phosphoribosyltransferase) be prioritized as a therap2026-04-22