Sabizabulin

Sabizabulin

Names
IUPAC name [2-(1H-Indol-3-yl)-1H-imidazol-5-yl]-(3,4,5-trimethoxyphenyl)methanone
Other names VERU-111
Identifiers
CAS Number	1332881-26-1
3D model (JSmol)	Interactive image
ChEMBL	ChEMBL2163631
ChemSpider	28642581
KEGG	D12519
PubChem CID	53379371
UNII	37L1JX37J5
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
SMILES COC1=CC(=CC(=C1OC)OC)C(=O)C2=CN=C(N2)C3=CNC4=CC=CC=C43
Properties
Chemical formula	C21H19N3O4
Molar mass	377.400 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Sabizabulin is a chemical compound from the group of indole and imidazole derivatives that was first reported in 2012 by Dalton, Li, and Miller. It is being studied as a mitotic inhibitor and chemotherapeutic agent in castration-resistant metastatic prostate cancer and in SARS-CoV-2 (COVID-19) infections.

Properties

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. 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.

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.

Research

COVID-19 therapy

In a phase III study on the treatment of severe courses of COVID-19, sabizabulin reduced mortality by 55% according to the manufacturer. 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.

Further reading

• Deng S, Krutilina RI, Wang Q, Lin Z, Parke DN, Playa HC, et al. (February 2020). "An Orally Available Tubulin Inhibitor, VERU-111, Suppresses Triple-Negative Breast Cancer Tumor Growth and Metastasis and Bypasses Taxane Resistance". Mol Cancer Ther. 19 (2): 348–363. doi:10.1158/1535-7163.MCT-19-0536. PMC 7007836. PMID 31645441.

External links

• "Sabizabulin". Drug Information Portal. U.S. National Library of Medicine.