Sabizabulin

Sabizabulin

Sabizabulin

Chemical compound

Quick Facts Names, Identifiers ...

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][medical citation needed]

References

  1. [1]
    "Substance Name: Sabizabulin". ChemIDplus. Retrieved 1 May 2022.
  2. [2]
    "Sabizabulin for COVID-19". Veru Inc. 14 January 2022. Retrieved 1 May 2022.
  3. [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. [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. [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.
  6. [6]
    rme (13 April 2022). "COVID-19: Krebsmittel Sabizabulin halbiert Sterberate bei schweren Erkrankungen". aerzteblatt.de. Retrieved 14 April 2022.
  7. [7]
    "Sabizabulin for Breast Cancer". Veru Inc. Retrieved 17 May 2022.
  8. [8]
    "Sabizabulin (Code C158517)". NCI Thesaurus. Retrieved 14 April 2022.
  9. [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. [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.
  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. [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.

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