Sabizabulin Explained

Legal Status:Investigational
Cas Number:1332881-26-1
Pubchem:53379371
Chemspiderid:28642581
Unii:37L1JX37J5
Kegg:D12519
Chembl:2163631
Synonyms:VERU-111[1] [2]
Iupac Name:[2-(1H-indol-3-yl)-1H-imidazol-5-yl]-(3,4,5-trimethoxyphenyl)methanone
C:21
H:19
N:3
O:4
Smiles:COC1=CC(=CC(=C1OC)OC)C(=O)C2=CN=C(N2)C3=CNC4=CC=CC=C43
Stdinchi: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)
Stdinchikey:WQGVHOVEXMOLOK-UHFFFAOYSA-N

Sabizabulin is an investigational new drug that is being evaluated for the treatment of castration-resistant prostate cancer[3] and in SARS-CoV-2 (COVID-19) infections.[4] It is a tubulin polymerization inhibitor.[5] [6]

Sabizabulin is chemical compound from the group of indole and imidazole derivatives that was first reported in 2012 by Dalton, Li, and Miller.[7]

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.[8] 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.[9]

Research

COVID-19 therapy

In a phase III study on the treatment of severe courses of COVID-19,[10] [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]

Further reading

Notes and References

  1. Web site: Substance Name: Sabizabulin . ChemIDplus . 1 May 2022.
  2. Web site: Sabizabulin for COVID-19 . Veru Inc. . 14 January 2022 . 1 May 2022.
  3. Markowski MC, Tutrone R, Pieczonka C, Barnette KG, Getzenberg RH, Rodriguez D, Steiner MS, Saltzstein DR, Eisenberger MA, Antonarakis ES . A Phase Ib/II 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 . 2789–2795 . July 2022 . 35416959 . 9774054 . 10.1158/1078-0432.CCR-22-0162 . 248128050 .
  4. Web site: COVID-19: Krebsmittel Sabizabulin halbiert Sterberate bei schweren Erkrankungen . COVID-19: Cancer drug Sabizabulin halves death rate in severe cases . aerzteblatt.de. 2022-04-14. rme. 13 April 2022.
  5. Web site: Sabizabulin - Veru Healthcare . AdisInsight . Springer Nature Switzerland AG .
  6. Mahmud F, Deng S, Chen H, Miller DD, Li W . Orally available tubulin inhibitor VERU-111 enhances antitumor efficacy in paclitaxel-resistant lung cancer . Cancer Letters . 495 . 76–88 . December 2020 . 32920198 . 7669640 . 10.1016/j.canlet.2020.09.004 .
  7. Li CM, Lu Y, Chen J, Costello TA, Narayanan R, Dalton MN, Snyder LM, Ahn S, Li W, Miller DD, Dalton JT . Orally bioavailable tubulin antagonists for paclitaxel-refractory cancer . Pharmaceutical Research . 29 . 11 . 3053–3063 . November 2012 . 22760659 . 3646298 . 10.1007/s11095-012-0814-5 .
  8. Web site: Sabizabulin for Breast Cancer . 2022-05-17 . Veru Inc. . en-US.
  9. Web site: Sabizabulin . Code C158517 . NCI Thesaurus . U.S. National Cancer Institute . 2022-04-14 .
  10. 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 . 13 April 2021 . 1 May 2022.
  11. Web site: 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 . 1 May 2022 . 1 May 2022 . https://web.archive.org/web/20220501173559/https://verupharma.gcs-web.com/news-releases/news-release-details/veru-enrolls-first-patient-phase-3-clinical-trial-sabizabulin . dead .
  12. 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. . 11 April 2022 . 30 April 2022 . 16 April 2022 . https://web.archive.org/web/20220416004327/https://verupharma.gcs-web.com/news-releases/news-release-details/verus-novel-covid-19-drug-candidate-reduces-deaths-55 . dead .
  13. News: Rabin R . New Drug Slashed Deaths Among Patients With Severe Covid, Maker Claims . 21 April 2022 . The New York Times . 11 Apr 2022.
  14. 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 . Veru Inc. . GlobeNewswire . 25 April 2022 . 30 April 2022.

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Sabizabulin".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2025, A B Cryer, All Rights Reserved. Cookie policy.