In situ proteome profiling of C75, a covalent bioactive compound with potential anticancer activities

Area of Science:

• Biochemistry
• Oncology
• Chemical Biology

Background:

• C75 is a known inhibitor of fatty acid synthase (FASN) and carnitine palmitoyltransferase 1A (CPT1A).
• Identifying novel biological targets of C75 analogues is crucial for understanding its anticancer mechanisms and developing new therapeutics.

Purpose of the Study:

• To synthesize a library of cell-permeable, minimally tagged C75 analogues.
• To utilize these analogues to identify novel biological targets in human liver cancer cells.

Main Methods:

• Synthesis of C75 analogues with minimal tags for cell permeability.
• Application of these analogues in human liver cancer cell models.
• Identification of protein targets through biochemical assays.

Main Results:

• Successful synthesis of a library of C75 analogues.
• Identification of known C75 targets: FASN and CPT1A.
• Discovery of novel targets: PDIA3, TFRC, and GAPDH in liver cancer cells.

Conclusions:

• The study successfully identified both known and novel biological targets of C75 analogues.
• The identified targets, particularly PDIA3, TFRC, and GAPDH, represent potential therapeutic targets for human liver cancer.