SIRT3

NAD-dependent deacetylase sirtuin-3, mitochondrial

Score: 0.378 Price: $0.38 Medium Druggability Status: active Wiki: SIRT3

HYPOTHESES

2

PAPERS

10

KG EDGES

658

DEBATES

1

3D Protein Structure

🧬 SIRT3 — PDB 4FVT Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Medium

Score: 0.61

Clinical Stage

Phase II

Target Class

Enzyme

Safety

0.75

Druggability Analysis

Drug Development0.30

Structural Tractability0.85

Target Class0.85

Safety Profile0.75

Key Metrics

PDB Structures:

30

Known Drugs:

4

Approved:

0

In Clinical Trials:

0

Drug Pipeline (4 compounds)

Druggability Rationale: SIRT3 is moderately tractable (0.68 score) as an enzyme target with a well-characterized NAD+-binding pocket and established precedent for activation via both direct small-molecule activators (Honokiol) and indirect NAD+ precursor approaches (NR, NMN). The existence of clinical-stage compounds and the target's clear enzymatic mechanism support small-molecule druggability, though achieving selective SIRT3 activation over other sirtuins remains a key challenge.

Mechanism: Enzyme activation — enhancing SIRT3 deacetylase activity restores mitochondrial protein function and reduces oxidative stress

Drug Pipeline (4 compounds)

Known Drugs:

Nicotinamide Riboside (NR) (Clinical trials)

Nicotinamide Mononucleotide (NMN) (Clinical trials)

Honokiol (Preclinical)

Resveratrol (Phase II)

Structural Data:

PDB (30) ✓AlphaFold ✓Cryo-EM —

3GLR 4BN5 4HD8 5D7N 4FVT+25 more

UniProt: Q9NTG7

🧬 3D Protein Structure

🧬 SIRT3 — PDB 4FVT Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

SIRT3 selectivity is challenging due to structural homology with other NAD+-dependent sirtuins (SIRT1, SIRT4, SIRT5); off-target effects on cytoplasmic sirtuins could confound mitochondrial-specific outcomes. Mitochondrial localization provides a degree of inherent selectivity advantage, allowing indirect activation via NAD+ precursors to preferentially benefit SIRT3 without requiring direct isoform selectivity.

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

5

Completed

3

Total Enrollment

280

By Phase

NA: 4 · PHASE1: 3 · PHASE3: 1

Honokiol in Early-Stage Resectable Non-Small Cell Lung Cancer Recruiting

PHASE1 NCT06566443 n=15

Carcinoma, Non-Small-Cell Lung

Interventions: Honokiol

Sponsor: The Methodist Hospital Research Institute | Started: 2024-11-08

Possible Action of Resveratrol in Improving the Outcomes of IVF/ICSI in Couples With Unexplained Infertility Recruiting

NA NCT06481696 n=90

Unexplained Infertility

Interventions: Resveratrol-based multivitamin supplemen, Folic acid, IVF/ICSI

Sponsor: Andros Day Surgery Clinic | Started: 2024-06-01

The Effectiveness and Safety of Cleanser Containing Triethyl Citrate, Pyruvic Acid, Combination Cream Containing Triethy Not Yet Recruiting

PHASE3 NCT06775314 n=102

Acne Vulgaris

Interventions: Cleanser, Combination cream, spot cream

Sponsor: Dr.dr.Irma Bernadette, SpKK (K) | Started: 2025-03-01

Acute Effects of Nicotinamide Riboside on Polysomnography-Measured Sleep Structure in Healthy Adults Not Yet Recruiting

NA NCT07284225 n=20

Healthy Volunteers

Interventions: Nicotinamide Riboside (NR), Placebo

Sponsor: Eye & ENT Hospital of Fudan University | Started: 2025-12-20

Effect of Supplement on Appetite and GLP-1 Not Yet Recruiting

NA NCT06790771 n=25

Hunger

Interventions: High Dose Supplement, Low Dose Supplement, Placebo

Sponsor: Texas Christian University | Started: 2025-01-15

Nicotinamide Riboside on Mitochondrial Function in Li-Fraumeni Syndrome Completed

PHASE1 NCT03789175 n=1

Cancer, Skin Fibroblasts, Muscle Weakness

Interventions: Nicotinamide Riboside (NR)

Sponsor: National Heart, Lung, and Blood Institute (NHLBI) | Started: 2019-03-25

NAD-brain: a Pharmacokinetic Study of NAD Replenishment Therapy Completed

PHASE1 NCT05698771 n=12

Healthy

Interventions: Nicotinamide Riboside (NR), nicotinamide mononucleotide, Nicotinamide Riboside (NR)

Sponsor: Haukeland University Hospital | Started: 2022-09-17

Resveratrol and First-degree Relatives of Type 2 Diabetic Patients Completed

NA NCT02129595 n=15

Pre-diabetes

Interventions: placebo, resveratrol

Sponsor: Maastricht University Medical Center | Started: 2014-04

Linked Hypotheses (3)

SIRT3-Mediated Mitochondrial Deacetylation Failure with PINK1/Parkin Mitophagy Dysfunction0.738

Mitochondrial-Nuclear Epigenetic Cross-Talk Restoration0.701

SIRT3 gates microglial surveillance versus primed metabolism through mitochondrial deacetylation0.482

Linked Experiments (0)

No linked experiments

Scoring Dimensions

Knowledge Graph (20)

activates (4)

SLC7A11→SIRT3SIRT3→GPX4TFAM→SIRT3SIRT3→EGFR

inhibits (1)

interacts with (10)

PPARA→SIRT3ULK1→SIRT3STX17→SIRT3SQSTM1→SIRT3NOS3→SIRT3

▸ Show 5 more

STING1→SIRT3GLP1R→SIRT3SREBF1→SIRT3SIRT1→SIRT3KDM6B→SIRT3

therapeutic target (5)

SOD2→SIRT3PPARGC1A→SIRT3SIRT3→PRKAA1SIRT3→CREBBPSIRT3→FOXO1

Debate History (1)

Should SIRT3 (NAD-dependent deacetylase sirtuin-3, mitochondrial) be prioritized2026-04-22