FTF Inhibitors

Chemical inhibitors of FTF can exert their inhibitory effects through various biochemical and cellular mechanisms. Methotrexate is one such inhibitor that targets dihydrofolate reductase, an enzyme crucial for producing tetrahydrofolate. Since tetrahydrofolate is vital for thymidylate synthesis, its depletion directly impacts DNA methylation and replication, where FTF is active. Similarly, 5-Fluorouracil's metabolites obstruct thymidylate synthase, which leads to a reduction in thymidine monophosphate, a nucleotide necessary for DNA synthesis and repair, thereby affecting FTF functionality. Hydroxyurea adds to this by diminishing deoxyribonucleotide pools through its inhibition of ribonucleotide reductase, an action that interferes with DNA synthesis processes involving FTF. Trichostatin A, a histone deacetylase inhibitor, disrupts FTF's role in DNA transcription regulation by altering chromatin structure through increased acetylation of histones.

Further inhibition is seen with 3-Deazaneplanocin A, which hinders S-adenosylhomocysteine hydrolase, leading to the accumulation of S-adenosylhomocysteine, a by-product that can inhibit methylation processes where FTF is active. Paclitaxel disrupts cell division by stabilizing microtubules, and this interference can extend to DNA repair and replication mechanisms that require FTF. Camptothecin and Etoposide, both topoisomerase inhibitors, prevent DNA relegation and induce DNA breaks respectively, impeding replication and transcription processes that FTF is essential for. The PARP enzyme inhibitor Olaparib impairs DNA repair mechanisms, particularly the base excision repair pathway, potentially affecting FTF's involvement in these pathways. Gefitinib, by inhibiting EGFR tyrosine kinase, disrupts downstream signaling pathways that are crucial for cell cycle progression and DNA repair processes involving FTF. Cisplatin forms DNA adducts and cross-links, thereby interfering with DNA replication and transcription, processes where FTF plays a crucial role. Lastly, Chlorambucil, through its DNA alkylating action, causes strand breaks and cross-links that disrupt the replication and transcription activities dependent on FTF. Each of these chemicals, through their distinct actions, converge on the inhibition of FTF, affecting its role in cellular DNA-related functions.