TucaresolOther Names: 589C80 Drug Class: Immune Modulators
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(Compound details obtained from ChemIDplus Advanced1 and NIAID Therapeutics Database2)
Mechanism of Action: Immune modulator. Tucaresol, a substituted benzaldehyde, is a low-molecular-weight compound that enhances co-stimulatory signaling to CD4-positive T-cells. Immune induction is dependent on transient covalent bonding (Schiff base formation) between carbonyls and amines expressed on antigen presenting cell (APC) and T-cell surfaces. Tucaresol substitutes for the natural donor of carbonyl groups to mimic the transient bonding that is essential for T-cell activation.3-5
In preliminary studies, tucaresol has been shown to stimulate HIV-specific cytotoxic T lymphocyte responses and generation of naive T cells via thymopoiesis in patients receiving ART who have suppressed viremia. Tucaresol appears to specifically increase type 1 cytokine production. The clinical benefits of tucaresol use as an adjuvant agent to enhance immune response and restoration in patients receiving ART are still unknown.6-8
Half-life (T½): The tucaresol terminal elimination half-life ranged from 105 to 113 hours in a 200-mg single-dose study in healthy men and women who were not HIV-infected. (Tucaresol was administered orally on two separate occasions, under fed and fasted states).9
Resistance: In an analysis of HIV-1 envelope V3 sequences in viral specimens obtained from tucaresol-treated patients in a Phase I/II trial at study entrance and at Week 16, tucaresol administration was found to not accelerate V3 evolution.10
Study Identifiers: Not Available
Study Purpose: Pilot study to determine the safety and immunomodulating effects of tucaresol
Study Population: HIV-infected, treatment-experienced and treatment–naive participants in different stages of infection:
- Group A: Participants were on ART >1 year, with CD4 count 300-500 cells/mm3 and HIV RNA <80 copies/mL.
- Group B: Participants were treatment-naive, with CD4 count >500 cells/mm3 and HIV RNA >10,000 copies/mL.
- Group C: Participants were treatment-naive, with CD4 count >500 cells/mm3 and HIV RNA <10,000 copies/mL.
- Group D: Participants were on ART >1 year, with CD4 count <200 cells/mm3 and HIV RNA <80 copies/mL. (Participants were considered immunological non-responders.)
- Tucaresol 25 mg administered as a single dose during Week 1
- Tucaresol 25 mg once daily for 4 days during Week 4
- Tucaresol 50 mg once daily for 4 days during Week 8
- Tucaresol 100 mg once daily for 4 days during Week 12
Selected Study Results:
- Antivir Ther article, 2004: Immunomodulation induced by tucaresol in HIV infection: results of a 16 week pilot Phase I/II trial
- CROI, 2003: Positive Immunomodulatory Effects of Tucaresol in HIV-infected Patients: Results from a Phase I/II Trial after 40 Weeks of Follow-up
- CROI, 2004: Dynamics of T Cells Homeostasis Induced by Tucaresol
Other HIV-related clinical trials involving tucaresol have also been completed.
No serious adverse events were reported in patients who were receiving tucaresol as an adjuvant to ongoing ART (Groups A and D). In these patients, the most common adverse events were low-grade fever and mild constitutional symptoms.6
Tucaresol drug interactions are currently unknown.
- United States National Library of Medicine. ChemIDplus Advanced. Available at: http://chem.sis.nlm.nih.gov/chemidplus/rn/84290-27-7. Last accessed on June 23, 2016.
- National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. Available at: http://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Last accessed on June 23, 2016.
- Chen H, Rhodes J. Schiff base forming drugs: mechanisms of immune potentiation and therapeutic potential. J Mol Med (Berl). 1996 Sep;74(9):497-504. Available at: http://www.ncbi.nlm.nih.gov/pubmed/8892054. Last accessed on June 23, 2016.
- Rhodes J. Discovery of immunopotentiatory drugs: current and future strategies. Clin Exp Immunol. 2002 Dec;130(3):363-9. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1906540/. Last accessed on June 23, 2016.
- Rhodes J. Therapeutic potential of Schiff base-forming drugs. Expert Opin Investig Drugs. 1996 Mar;5(3):257-268 doi:10.1517/135437184.108.40.2067. Available at: http://informahealthcare.com/doi/abs/10.1517/135437220.127.116.117. Last accessed on June 23, 2016.
- Gori A, Trabattoni D, Bandera A, et al. Immunomodulation induced by tucaresol in HIV infection: results of a 16 week pilot Phase I/II trial. Antivir Ther. 2004 Aug;9(4):603-14. Available at: http://www.intmedpress.com/serveFile.cfm?sUID=51adea26-5a12-4d62-bca1-3164eb7a9222. Last accessed on June 23, 2016.
- Bandera A, Gori A, Trabattoni D, et al. Positive Immunomodulatory Effects of Tucaresol in HIV-infected Patients: Results from a Phase I/II Trial after 40 Weeks of Follow-up. Abstract presented at: 10th Conference on Retroviruses and Opportunistic Infections (CROI); February 10-14, 2003; Boston, MA. Abstract 654. Available at: http://www.aegis.org/DisaplayConf/?Abstract=107218. Last accessed on April 23, 2014.
- Gazzola L, Marchetti G, Bandera A, et al. Dynamics of T Cells Homeostasis Induced by Tucaresol. Abstract presented at: 11th Conference on Retroviruses and Opportunistic Infections (CROI); February 8-11, 2004; San Francisco, CA. Abstract 523. Available at: http://www.aegis.org/DisaplayConf/?Abstract=108015. Last accessed on April 23, 2014.
- Peck RW, Wootton R, Wiggs R, Layton G, Posner J. Effect of food and gender on the pharmacokinetics of tucaresol in healthy volunteers. Br J Clin Pharmacol. 1998 Jul;46(1):83-6. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1873973/. Last accessed on June 23, 2016.
- Bulgheroni E, Bandera A, Galli M, Gori A, Rusconi S. Analysis of the env V3 sequences obtained from patients with HIV type 1 infection treated with the immune modulant agent tucaresol. AIDS Res Hum Retroviruses. 2005 Sep;21(9):815-9. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16218807. Last accessed on June 23, 2016.
Last Reviewed: June 23, 2016