CMKLR1

Chemokine-like Receptor 1

Score: 0.586 Price: $0.59 Low Druggability Status: active Wiki: CMKLR1

🧠 Neurodegeneration

HYPOTHESES

PAPERS

KG EDGES

DEBATES

3D Protein Structure

🧬 CMKLR1 — PDB 5XSZ Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.41

Clinical Stage

Phase II

Target Class

Gpcr

Safety

0.60

Druggability Analysis

Drug Development0.30

Structural Tractability0.70

Target Class0.85

Safety Profile0.60

Key Metrics

PDB Structures:

Known Drugs:

Approved:

In Clinical Trials:

Drug Pipeline (3 compounds)

3 Preclinical

Therapeutic Areas:

Neuroinflammation Neurodegeneration (Alzheimer's disease, Parkinson's disease) Neuroimmune disorders Microglial activation disorders Inflammatory neuropathies

Druggability Rationale: CMKLR1 exhibits moderate druggability (0.60) as a validated GPCR target with substantial structural support including 5 PDB structures at 2.81 Å resolution and AlphaFold models, enabling rational drug design. However, the limited clinical advancement (Phase 2) and absence of approved therapeutics suggest challenges in selectivity, potency, or translating preclinical efficacy to clinically meaningful endpoints in neuroinflammatory indications.

Mechanism: GPCR antagonist or agonist modulating chemerin signaling

Drug Pipeline (3 compounds)

3 Preclinical

Known Drugs:

α-NETA (research_tool)

CCX832 (preclinical)

Chemerin-derived peptides (research_tool)

Structural Data:

PDB (5) ✓AlphaFold ✓Cryo-EM ✓

7YKD 8SG1 8ZJG 9L3W 9L3Z

UniProt: F8VYN7

Binding Pocket Analysis:

The orthosteric binding pocket is likely formed by transmembrane helices (TM3, TM5, TM6, TM7) typical of chemokine receptors, with structural data from 7YKD and related PDBs revealing potential allosteric modulation sites in the extracellular loops and intracellular regions. The moderate resolution (2.81 Å) and availability of multiple conformational states support structure-based optimization of both orthosteric antagonists and allosteric modulators.

🧬 3D Protein Structure

🧬 CMKLR1 — PDB 5XSZ Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

CMKLR1 selectivity against other chemokine receptors (CCR1-10, CX3CR1, XCR1) is critical given the high homology within GPCR chemokine receptor families; off-target immunomodulatory effects represent a significant risk. The presence of multiple structural conformations across PDB entries suggests potential for achieving ligand selectivity through conformational state targeting.