Recent trends in fragment-based anticancer drug design strategies against different targets: A mini-review

Area of Science:

• Oncology
• Medicinal Chemistry
• Drug Discovery

Background:

• Cancer remains a significant global health challenge, with chemotherapy as a primary treatment modality.
• Developing new chemotherapeutic agents faces high attrition rates due to challenges in targeting specific proteins.
• Structure-based drug design, particularly Fragment-Based Drug Design (FBDD), presents a promising approach to mitigate these issues.

Purpose of the Study:

• To review computational and experimental Fragment-Based Drug Design (FBDD) techniques for developing anticancer molecules.
• To highlight FBDD strategies targeting key cancer-related proteins such as aurora kinase, PDK1, STAT3, Mcl-1, TNKS, choline kinase, protein kinase, tyrosine kinase, and LSD1.
• To provide insights for the scientific community on utilizing FBDD for lead identification over high-throughput screening (HTS).

Main Methods:

• Review of computational FBDD methodologies.
• Analysis of experimental FBDD techniques.
• Compilation of FBDD strategies applied to various cancer targets.

Main Results:

• FBDD has proven successful in designing molecules with anticancer properties.
• Various cancer targets, including kinases and demethylases, are amenable to FBDD approaches.
• FBDD offers a viable alternative to HTS for identifying potent drug leads.

Conclusions:

• Fragment-Based Drug Design (FBDD) is an effective strategy for developing targeted cancer therapies.
• The review consolidates FBDD approaches for multiple critical cancer targets.
• FBDD is poised to become a preferred method for anticancer drug discovery, enhancing efficiency and reducing development failures.