Zinc Finger Inhibitor 2015
From Bruce E. Torbett • David S.
Goodsell Douglas • D. Richman
of HIV-1 Therapeutics
Due to their potent antiviral activity in vitro, several attempts were made to evaluate
the potential therapeutic use of zinc ejectors in vivo. To our knowledge, only two
zinc ejectors, namely ADA and benzisothiazolone, were tested in clinical studies.
Due to its toxicity, assays with the second compound were rapidly stopped (Turpin
2003). Preclinical tolerance assays showed that oral doses of 1.5 g ADA daily for
1 month were well tolerated, with no evidence of adverse effects (Vandevelde et al.
1996). Then, ADA was administrated three times daily during 3 months in addition
to other antiviral therapy to fifteen individuals with advanced AIDS within a Phase
I/II clinical trial.
Library of Congress Control
Number: 2015937951 Springer Cham Heidelberg New York Dordrecht London © Springer
International Publishing Switzerland 2015
US government) (click on NIAID searchable database and submit Azodicarbonamide) http://www.niaid.nih.gov/
Vandevelde M, Witvrouw M, Schmit JC, Sprecher S, De Clercq E, Tassignon JP ADA,
a potential anti-HIV drug. AIDS Res Hum Retroviruses. 1996 May 1; 12(7):567-8 ADA , a Potential Anti-HIV Drug. ADA (l,l'-azobisformamide) is the abbreviated name for an azoic compound with the following structural formula (MW = 116.08). As formal clinical studies are about to start in AIDS patients with ADA, we report for the first time pre-clinical results of studies showing that ADA is inhibitory to the replication of HIV-1 and is a virucidal agent in vitro.
In conclusion, ADA may be considered as a potential anti-HIV drug. It may be targeted at a post-transcriptional stage of retroviral replication. It has a very low in vivo toxicity. Thus, ADA, suitably formulated pharmaceutically, represents an interesting new investigational compound for the treatment and/or prophylaxis of AIDS in man. ADA could be used in combination with RT inhibitors (DDI, d4T). M. Vandevelde Hubriphar SA Brussels. Belgium. M. Witvrouw J.C. Schmit AIDS Laboratory Rcga Institute of Medical Research Kalhotieke Universiteit Leuven Leuven, Belgium S. Sprecher Institut Pasteur Brussels, Belgium http://www.ncbi.nlm.nih.gov/
Rice, W.G., Turpin, J.A., Huang, M., Clanton, D., Buckheit, R.W., Covell, D.G.,
Wallquist, A., McDonnell, N.B., DeGuzman, R.N., Summers, M.F., Zalkow, L., Bader, J.P., Haugwitz, R.D. and Sausville, E.A. Azodicarbonamide inhibits HIV-1 replication by targeting the nucleocapsid protein without affecting cellular zinc finger proteins. Nature Medicine 3, 341-345 (1997). http://www.ncbi.nlm.nih.gov/
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Rice, W.G.; Huang, M.; McDonnell, N.; Summers, M.F.; Turpin, J.A. , pp. A55
Targeting the HIV-1 Nucleocapsid Protein by Azodicarbonamide ( ADA), Cystamine, and Dithiane Compounds Antiviral Research, Vol: 34, Issue: 2, April 1997 http://www1.elsevier.com/
Garber ME, Wei P, Kewal Ramani VN, Mayall TP, Herrmann CH, Rice AP, Littman DR, Jones KA
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Nancy A. Jewell (2) and Louis M. Mansky (1)
In the beginning: genome recognition, RNA encapsidation and the initiation of complex retrovirus assembly (1) Department of Molecular Virology, Immunology, and Medical Genetics, Center for Retrovirus Research, and Comprehensive Cancer Center, Ohio State University Medical Center, Journal of General Virology (2000), 81 , 18891899. 2078 Graves Hall, 333 West 10th Ave, Columbus, OH 43210, USA(2)Molecular, Cellular, and Developmental Biology Graduate Program, Ohio State University, USA http://vir.sgmjournals.org/
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Phase I/II dose escalation and randomized withdrawal study with add-on Azodicarbonamide in patients failing on current antiretroviral therapy. AIDS. 2001 Jan 5; 15(1):33-45. http://www.ncbi.nlm.nih.gov/
EDITORIALS Scott A. Foster, William C. Phelps
Zn 2+ Fingers and Cervical Cancer Journal of the National Cancer Institute, Vol. 91, No. 14, 1180-1181, July 21, 1999 http://jncicancerspectrum.oupjournals.org/
Walter Beerheide, Hans-Ulrich Bernard, Yee-Joo Tan, Arasu Ganesan, William G.Rice, Anthony E. Ting
Potential Drugs Against Cervical Cancer: Zinc-Ejecting Inhibitors of the Human Papillomavirus Type 16 E6 Oncoprotein Journal of the National Cancer Institute, Vol. 91, No. 14, July 21, 1999 pp 1211-1220 http://jncicancerspectrum.oupjournals.org/
Tassignon J, Ismaili J, Le Moine A,Van Laethem F, Leo,Vandevelde M, Goldman M.
Azodicarbonamide inhibits T-cell responses in vitro and in vivo. Nat Med. 1999 Aug;5 (8):947-50. http://www.ncbi.nlm.nih.gov/
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Interactions between human immunodeficiency virus type 1 reverse transcriptase, tRNA primer, and nucleocapsid protein during reverse transcription. J Hum Virol 2000 Jan-Feb;3(1):16-26 http://www.ncbi.nlm.nih.gov/
Teresa A. Bennett, Bruce S. Edwards,Larry A. Sklar, and Snezna Rogelj
Sulfhydryl Regulation of L-Selectin Shedding: Phenylarsine Oxide Promotes Activation-Independent L-Selectin Shedding from Leukocytes1. The Journal of Immunology, 2000, 164: 4120–4129. http://www.jimmunol.org/
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Azodicarbonamide as a new T cell immunosuppressant: synergy with cyclosporin A. Clin Immunol. 2001 Jul;100(1):24-30. http://www.ncbi.nlm.nih.gov/
Christine Fagny, Michel Vandevelde, Michal Svoboda and Patrick Robberecht Ribonucleotide
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Interactions of Azodicarbonamide ( ADA) species with the model zinc finger site: Theoretical support of the zinc finger domain destruction in the HIV-1 nucleocapsid protein (NCp7) by ADA J.Phys.Chem.B, 2001, V.105, P.11341-11350. http://lcc.chem.msu.ru/anem/
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