How many protein pairs can we chemically target?

Area of Science:

• Pharmacology
• Biochemistry
• Drug Discovery

Background:

• Drugs often interact with multiple targets, both intended and unintended.
• Multi-target drugs are increasingly approved, accounting for ~20% of new drugs in the last 25 years.
• Understanding drug-target interactions is crucial for therapeutic development.

Purpose of the Study:

• To catalogue chemically targeted and targetable protein pairs.
• To identify opportunities for designing novel dual-action drugs.
• To explore co-expressed and phylogenetically related protein combinations.

Main Methods:

• Analysis of existing drug-target interaction databases.
• Identification of co-expressed protein pairs.
• Assessment of phylogenetic relationships between proteins.
• Filtering for pairs with known drugs or bioactive ligands, and those with potential.

Main Results:

• A catalogue of 64,222 chemically targeted protein pairs was identified.
• An additional 7,253 potentially targetable protein pairs were discovered.
• These pairs represent 5% of all co-expressed dual protein combinations with known ligands.

Conclusions:

• The compiled catalogue provides extensive opportunities for designing future dual-action drugs.
• This resource can guide systematic development of therapeutics targeting multiple proteins.
• The findings highlight the potential for novel drug discovery through multi-target strategies.