Protein farnesyltransferase inhibitors

Area of Science:

• Oncology
• Molecular Biology
• Drug Discovery

Background:

• Mutations in the ras gene lead to uncontrolled cell growth and cancer by impairing guanosine triphosphatase (GTPase) activity.
• Ras protein transformation requires posttranslational modification and plasma membrane association, making the prenylation process a key target.

Purpose of the Study:

• To review the progress of protein farnesyltransferase (FTase) inhibitors in drug discovery and clinical development.
• To highlight FTase as a therapeutic target for cancers and other diseases linked to aberrant protein prenylation.

Main Methods:

• Review of scientific literature on FTase inhibitors, including in vitro and in vivo studies.
• Analysis of drug discovery efforts, structural biology insights, and clinical trial data for FTase inhibitors.

Main Results:

• Small-molecule FTase inhibitors demonstrate efficacy and low toxicity in preclinical models of ras-dependent tumors.
• FTase inhibitors are being investigated for their potential to suppress angiogenesis and induce apoptosis, offering indirect anti-tumor effects.
• Several FTase inhibitors have advanced to clinical trials, with some in Phase II and Phase III studies.

Conclusions:

• FTase is a validated therapeutic target, with inhibitors showing significant promise in preclinical and clinical settings.
• Advancements in structural biology have facilitated the design of potent and diverse FTase inhibitors.
• Ongoing clinical trials will determine the ultimate efficacy and safety of FTase inhibitors in treating various diseases, particularly cancer.