Sabizabulin
Chemical compound
From Wikipedia, the free encyclopedia
Sabizabulin is an investigational new drug that is being evaluated for the treatment of castration-resistant prostate cancer[4] and in SARS-CoV-2 (COVID-19) infections.[5] It is a tubulin polymerization inhibitor.[6][7]
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| Other names | VERU-111[1][2][3] |
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| Formula | C21H19N3O4 |
| Molar mass | 377.400 g·mol−1 |
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Sabizabulin is chemical compound from the group of indole and imidazole derivatives that was first reported in 2012 by Dalton, Li, and Miller.[8]
Pharmacology
Pharmacokinetics
Sabizabulin is not a substrate of P-glycoprotein (Pgp), an efflux pump that, when overexpressed, can confer resistance to taxanes, a group of widely used cancer therapeutics.
Mechanism of action
Sabizabulin, as an orally available molecule, acts on microtubules, a component of the cytoskeleton. It binds to the colchicine binding site on the beta subunit of tubulin, as well as a novel site on the alpha subunit, and causes both to crosslink, thus depolymerizing microtubules and preventing their polymerization.[9] By preventing mitotic spindle formation, this directly inhibits mitosis of tumor cells and endothelial cells attempting to form new blood vessels to feed them. In parallel, microtubule-mediated trafficking of cellular components (including androgen receptors into the nucleus), thus, a potential anti-androgen agent. The transport of viral particles (including SARS-CoV-2) may also be inhibited. These activities can inhibit viral replication and assembly. Inhibition of tubulin polymerization can also inhibit the release of pro-inflammatory cytokines and disrupt the activities of inflammatory cells.[10]
Research
COVID-19 therapy
In a phase III study on the treatment of severe courses of COVID-19,[3][11] sabizabulin reduced mortality by 55% according to the manufacturer.[12] Because of the high efficacy, the test phase was stopped prematurely so that the drug no longer had to be withheld from the placebo control group.[13][14][medical citation needed]
