Sabizabulin

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]

Sabizabulin

Clinical data
Other names	VERU-111[1][2][3]
Identifiers
IUPAC name [2-(1H-indol-3-yl)-1H-imidazol-5-yl]-(3,4,5-trimethoxyphenyl)methanone
CAS Number	1332881-26-1
PubChem CID	53379371
ChemSpider	28642581
UNII	37L1JX37J5
KEGG	D12519
ChEMBL	ChEMBL2163631
Chemical and physical data
Formula	C21H19N3O4
Molar mass	377.400 g·mol−1
3D model (JSmol)	Interactive image
SMILES COC1=CC(=CC(=C1OC)OC)C(=O)C2=CN=C(N2)C3=CNC4=CC=CC=C43
InChI InChI=1S/C21H19N3O4/c1-26-17-8-12(9-18(27-2)20(17)28-3)19(25)16-11-23-21(24-16)14-10-22-15-7-5-4-6-13(14)15/h4-11,22H,1-3H3,(H,23,24) Key:WQGVHOVEXMOLOK-UHFFFAOYSA-N

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]}