ARL6 Inhibitors

Chemical inhibitors of ARL6 operate by targeting the microtubule network within cells, which is essential for the proper function of ARL6. Colchicine, Vinblastine, Nocodazole, Vincristine, Podophyllotoxin, Eribulin, Griseofulvin, and Albendazole all disrupt microtubule polymerization or stability in different ways. Colchicine binds to tubulin, the building block of microtubules, thereby preventing its polymerization and leading to the depolymerization of microtubules. This action can inhibit ARL6 by impeding its trafficking and localization capabilities. Similarly, Vinblastine interferes with microtubule assembly by binding to tubulin, which can lead to the inhibition of ARL6 as it relies on intact microtubules for the transport of its cargo. Nocodazole also targets tubulin and disrupts microtubule dynamics, hampering the transport mechanisms necessary for ARL6 function. Vincristine, another microtubule-targeting agent, inhibits tubulin polymerization, which is likely to inhibit ARL6-dependent transport processes.

In the second approach, chemicals like Paclitaxel, Taxol, and Peloruside A stabilize microtubules, which can inhibit ARL6 by preventing the microtubule dynamics that are essential for its function. By binding to β-tubulin, Paclitaxel enhances microtubule assembly while simultaneously inhibiting their disassembly, which can lead to the inhibition of ARL6 by disrupting the normal dynamic state of microtubules required by ARL6. Taxol, a well-known microtubule stabilizer, likely inhibits ARL6 in a similar manner. Peloruside A also stabilizes microtubules and thus could inhibit ARL6 by altering the microtubule dynamics that ARL6 utilizes for its intracellular functions. Podophyllotoxin, acting through a different mechanism, binds to tubulin and inhibits its polymerization, which can prevent ARL6 from performing its transport functions effectively. Eribulin inhibits the growth phase of microtubules without affecting the shortening phase, leading to dysfunctional microtubule networks and likely inhibiting ARL6. Griseofulvin binds to microtubules and interferes with their function, which can inhibit ARL6 by disrupting cellular transport pathways. Lastly, Noscapine alters microtubule dynamics, leading to the inhibition of ARL6 by disrupting the proper functioning of the microtubule-based transport system that ARL6 relies on.