Combined Ligand-Based and Structure-Based Virtual Screening Approach for Identification of New Dipeptidyl Peptidase 4...

Area of Science:

• Medicinal Chemistry
• Computational Chemistry
• Pharmacology

Background:

• Dipeptidyl Peptidase 4 (DPP 4) is a key enzyme in glucose regulation, targeted for Type 2 Diabetes treatment.
• Approved DPP 4 inhibitors, known as 'gliptins', are widely used.
• Identifying novel DPP 4 inhibitors is crucial for advancing diabetes management.

Purpose of the Study:

• To identify novel inhibitors of Dipeptidyl Peptidase 4 (DPP 4) using computational screening.
• To explore new chemical entities for potential Type 2 Diabetes therapeutics.

Main Methods:

• A combined pharmacophore and docking-based virtual screening protocol was employed.
• The Specs commercial database was searched using a validated pharmacophore model.
• Selected compounds underwent in-vitro DPP 4 enzyme inhibition assays.

Main Results:

• Virtual screening identified potential DPP 4 inhibitors with predicted binding interactions.
• Three compounds (AN-465/42837213, AP-064/42049348, AN-465/43369427) demonstrated moderate DPP 4 enzyme inhibition.
• Docking studies indicated similar binding orientations to reference molecules.

Conclusions:

• In-silico tools successfully identified novel DPP 4 inhibitors.
• The identified compounds serve as promising starting points for developing new DPP 4 inhibitor drugs.
• This approach accelerates the discovery of potential Type 2 Diabetes treatments.