BMAL1

Basic Helix-Loop-Helix ARNT Like 1

Score: 0.541 Price: $0.54 Low Druggability Status: active Wiki: BMAL1

🧠 Neurodegeneration

HYPOTHESES

PAPERS

KG EDGES

778

DEBATES

3D Protein Structure

🧬 BMAL1 — PDB 4F3L Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.34

Clinical Stage

Phase I

Target Class

Transcription Factor

Safety

0.30

Druggability Analysis

Drug Development0.15

Structural Tractability0.85

Target Class0.50

Safety Profile0.30

Key Metrics

PDB Structures:

Known Drugs:

Approved:

In Clinical Trials:

Drug Pipeline (4 compounds)

4 Preclinical

Druggability Rationale: BMAL1 demonstrates medium druggability (0.55) with genuine tractability potential despite being a transcription factor, a traditionally challenging class. The availability of 10 PDB structures at 1.83 Å resolution, combined with validated preclinical modulators (SR9009, SR9011, KL001, Nobiletin) that achieve circadian modulation through small molecules, indicates an exploitable binding pocket and feasible chemistry; however, transcription factor engagement typically requires high potency and selectivity to avoid pleiotrophic effects.

Mechanism: Small molecule modulator of circadian transcription

Drug Pipeline (4 compounds)

4 Preclinical

Known Drugs:

SR9009 (preclinical)

SR9011 (preclinical)

KL001 (preclinical)

Nobiletin (preclinical)

Structural Data:

PDB (10) ✓AlphaFold ✓Cryo-EM —

4F3L 4H10 8OSJ 8OSK 8OSL+5 more

UniProt: E9PL54

🧬 3D Protein Structure

🧬 BMAL1 — PDB 4F3L Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

Key selectivity challenge involves distinguishing BMAL1 modulation from its heterodimerization partner CLOCK and other bHLH-PAS family members, which share structural homology and overlapping DNA-binding domains. Off-target circadian disruption in peripheral tissues must be carefully evaluated, as systemic BMAL1 inhibition can impair metabolic homeostasis; tissue-selective delivery or isoform-selective binding may be necessary.