Keratin 74 Inhibitors

Chemical inhibitors of Keratin 74 can disrupt its production by targeting various stages of the cell cycle and cellular mechanisms essential for DNA replication, transcription, and cell division. Methotrexate, for example, acts by inhibiting the enzyme dihydrofolate reductase, crucial for thymidine synthesis and therefore DNA replication. This action can lead to a reduced capacity for cell division in the hair follicle cells responsible for producing Keratin 74. Similarly, Hydroxyurea impedes the action of ribonucleotide reductase, diminishing the pool of deoxyribonucleotides necessary for DNA synthesis and thus can reduce the proliferation of these specific cells. Cytarabine incorporates itself into DNA, resulting in premature chain termination during DNA synthesis, which can directly decrease the incorporation of Keratin 74 as the cell cycle is halted. Aphidicolin, by selectively inhibiting DNA polymerases alpha and delta, can result in an S-phase arrest, thereby inhibiting the synthesis of Keratin 74 by affecting the proliferative capacity of the cells. In addition to inhibitors that target DNA synthesis, other chemicals interfere with the structural components required for cell division. Paclitaxel and Vinblastine disrupt microtubule dynamics, an essential part of the cell's cytoskeleton necessary for mitosis. Paclitaxel stabilizes microtubules, preventing their disassembly and leading to cell cycle arrest, while Vinblastine prevents microtubule formation. Both actions can result in decreased cell proliferation and, hence, reduced production of Keratin 74. Podophyllotoxin and Colchicine also target tubulin and inhibit microtubule polymerization, leading to similar outcomes in terms of cell cycle arrest and can lead to a reduction in Keratin 74 synthesis. Furthermore, chemicals like Camptothecin, Etoposide, and Bleomycin introduce breaks or interfere with the proper segregation of DNA during replication and transcription. Camptothecin inhibits topoisomerase I, and Etoposide inhibits topoisomerase II, while Bleomycin causes DNA strand breakage, all of which can lead to a decrease in cell proliferation and subsequent Keratin 74 production. Lastly, Bortezomib disrupts the degradation of regulatory proteins by inhibiting the proteasome, leading to cell cycle arrest and can limit the survival of cells that produce Keratin 74, further contributing to the decrease in its production.