Sabizabulin

Sabizabulin
Names
	IUPAC name [2-(1H-Indol-3-yl)-1H-imidazol-5-yl]-(3,4,5-trimethoxyphenyl)methanone
	Other names VERU-111[1][2][3]
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.[4] It is being studied as a mitotic inhibitor and chemotherapeutic agent in castration-resistant metastatic prostate cancer[5] and in SARS-CoV-2 (COVID-19) infections.[6]

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.[7] 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.[8]

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,[3][9] sabizabulin reduced mortality by 55% according to the manufacturer.[10] 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.[11][12]

References

"Substance Name: Sabizabulin". ChemIDplus. Retrieved 1 May 2022.
"Sabizabulin for COVID-19". Veru Inc. 14 January 2022. Retrieved 1 May 2022.
"VERU-111 in the Treatment of SARS-Cov-2 Infection by Assessing Its Effect on the Proportion of Patients Who Die on Study". ClinicalTrials.gov (Press release). 13 April 2021. Retrieved 1 May 2022.
Li, Chien-Ming; Lu, Yan; Chen, Jianjun; Costello, Terrence A.; Narayanan, Ramesh; Dalton, Mara N.; et al. (4 July 2012). "Orally Bioavailable Tubulin Antagonists for Paclitaxel-Refractory Cancer". Pharmaceutical Research. 29 (11): 3053–3063. doi:10.1007/s11095-012-0814-5. ISSN 0724-8741. PMC 3646298. PMID 22760659.
Markowski MC, Tutrone R, Pieczonka C, Barnette KG, Getzenberg RH, Rodriguez D, et al. (April 2022). "A Phase 1b/2 Study of Sabizabulin, a Novel Oral Cytoskeleton Disruptor, in Men With Metastatic Castration-Resistant Prostate Cancer with Progression on an Androgen Receptor Targeting Agent". Clinical Cancer Research. 28 (13): OF1–OF7. doi:10.1158/1078-0432.CCR-22-0162. PMC 9774054. PMID 35416959. S2CID 248128050.
rme (13 April 2022). "COVID-19: Krebsmittel Sabizabulin halbiert Sterberate bei schweren Erkrankungen". aerzteblatt.de. Retrieved 14 April 2022.
"Sabizabulin for Breast Cancer". Veru Inc. Retrieved 17 May 2022.
"Sabizabulin (Code C158517)". NCI Thesaurus. Retrieved 14 April 2022.
"Veru Enrolls First Patient in Phase 3 Clinical Trial of Sabizabulin (VERU-111) in High Risk Hospitalized COVID-19 Patients". Veru Inc. 19 May 2021. Retrieved 1 May 2022.
"Veru's Novel COVID-19 Drug Candidate Reduces Deaths by 55% in Hospitalized Patients in Interim Analysis of Phase 3 Study; Independent Data Monitoring Committee Halts Study Early for Overwhelming Efficacy". Veru Inc. (Press release). 11 April 2022. Retrieved 30 April 2022.
Rabin, Roni (11 April 2022). "New Drug Slashed Deaths Among Patients With Severe Covid, Maker Claims". The New York Times. Retrieved 21 April 2022.
"Veru Announces Oral Late-Breaking Presentation of Phase 2 Data of Sabizabulin for the Treatment of Hospitalized Severe COVID-19 Patients at High Risk for Acute Respiratory Distress Syndrome at the 32nd European Congress of Clinical Microbiology & Infectious Diseases" (Press release). Veru Inc. 25 April 2022. Retrieved 30 April 2022 – via GlobeNewswire.

External links

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

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[1] "Substance Name: Sabizabulin". ChemIDplus. Retrieved 1 May 2022.

[2] "Sabizabulin for COVID-19". Veru Inc. 14 January 2022. Retrieved 1 May 2022.

[NCT04842747-3] "VERU-111 in the Treatment of SARS-Cov-2 Infection by Assessing Its Effect on the Proportion of Patients Who Die on Study". ClinicalTrials.gov (Press release). 13 April 2021. Retrieved 1 May 2022.

[4] Li, Chien-Ming; Lu, Yan; Chen, Jianjun; Costello, Terrence A.; Narayanan, Ramesh; Dalton, Mara N.; et al. (4 July 2012). "Orally Bioavailable Tubulin Antagonists for Paclitaxel-Refractory Cancer". Pharmaceutical Research. 29 (11): 3053–3063. doi:10.1007/s11095-012-0814-5. ISSN 0724-8741. PMC 3646298. PMID 22760659.

[5] Markowski MC, Tutrone R, Pieczonka C, Barnette KG, Getzenberg RH, Rodriguez D, et al. (April 2022). "A Phase 1b/2 Study of Sabizabulin, a Novel Oral Cytoskeleton Disruptor, in Men With Metastatic Castration-Resistant Prostate Cancer with Progression on an Androgen Receptor Targeting Agent". Clinical Cancer Research. 28 (13): OF1–OF7. doi:10.1158/1078-0432.CCR-22-0162. PMC 9774054. PMID 35416959. S2CID 248128050.

[AB-6] rme (13 April 2022). "COVID-19: Krebsmittel Sabizabulin halbiert Sterberate bei schweren Erkrankungen". aerzteblatt.de. Retrieved 14 April 2022.

[7] "Sabizabulin for Breast Cancer". Veru Inc. Retrieved 17 May 2022.

[NCI-8] "Sabizabulin (Code C158517)". NCI Thesaurus. Retrieved 14 April 2022.

[9] "Veru Enrolls First Patient in Phase 3 Clinical Trial of Sabizabulin (VERU-111) in High Risk Hospitalized COVID-19 Patients". Veru Inc. 19 May 2021. Retrieved 1 May 2022.

[10] "Veru's Novel COVID-19 Drug Candidate Reduces Deaths by 55% in Hospitalized Patients in Interim Analysis of Phase 3 Study; Independent Data Monitoring Committee Halts Study Early for Overwhelming Efficacy". Veru Inc. (Press release). 11 April 2022. Retrieved 30 April 2022.

[Rabin,_NYT_2022.04.11-11] Rabin, Roni (11 April 2022). "New Drug Slashed Deaths Among Patients With Severe Covid, Maker Claims". The New York Times. Retrieved 21 April 2022.

[12] "Veru Announces Oral Late-Breaking Presentation of Phase 2 Data of Sabizabulin for the Treatment of Hospitalized Severe COVID-19 Patients at High Risk for Acute Respiratory Distress Syndrome at the 32nd European Congress of Clinical Microbiology & Infectious Diseases" (Press release). Veru Inc. 25 April 2022. Retrieved 30 April 2022 – via GlobeNewswire.