Keratin 83 Inhibitors

Chemical inhibitors of Keratin 83 include a variety of compounds that primarily target the cytoskeletal components with which Keratin 83 interacts, thereby inhibiting its function. Phalloidin, a toxin that binds to F-actin, can inhibit Keratin 83's ability to maintain the structural integrity of the cytoskeleton by stabilizing actin filaments and preventing their disassembly, which is crucial for the dynamic restructuring of the cytoskeleton. Withaferin A disrupts the cytoskeleton by modifying annexin II, which in turn can prevent Keratin 83 from fulfilling its structural role within the cell. Swinholide A and Cytochalasin D disrupt the actin cytoskeleton, with Swinholide A severing actin filaments and Cytochalasin D capping the barbed ends of actin filaments, inhibiting their elongation. This can lead to a compromised cytoskeletal structure, thereby inhibiting Keratin 83's interaction with actin.

Jasplakinolide and Latrunculin A also target actin dynamics; Jasplakinolide stabilizes actin filaments, reducing their turnover which can inhibit Keratin 83's functionality, whereas Latrunculin A sequesters actin monomers, inhibiting their polymerization, which is necessary for Keratin 83 to maintain cellular structural integrity. Chelidonine and Griseofulvin target tubulin and microtubule dynamics, where Chelidonine interacts with tubulin to inhibit its polymerization, and Griseofulvin binds to tubulin, causing microtubule destabilization, both potentially leading to a perturbed interaction of Keratin 83 with the cytoskeleton. Colchicine, Vinblastine, and Nocodazole also disrupt microtubule formation, with Colchicine and Vinblastine directly binding to tubulin, and Nocodazole disrupting the microtubule network, all of which can inhibit the proper organization and function of Keratin 83 within the cell. Paclitaxel, in contrast, stabilizes microtubules excessively, which could impair the dynamic interaction between Keratin 83 and the cytoskeleton, essential for the proper function of Keratin 83. Each of these chemical inhibitors, by altering the stability and dynamics of the cytoskeleton, can exert a functional inhibitory effect on Keratin 83.