The development of pyrrolobenzodiazepines as antitumour agents

Expert Opinion on Investigational Drugs
John A Hartley


DNA interacting agents play a major role in cancer chemotherapy, either as single agents, in combination drug regimens, or as components of novel targeted therapies. The search for more selective and efficacious drugs that can deliver critical DNA damage with minimal side effects continues. The development of the pyrrolobenzodiazepines (PBDs) from their discovery as natural products in the 1960s, through synthetic PBD monomers, PBD hybrids and conjugates, and PBD dimers is described. The latter molecules are capable of forming sequence selective, non-distorting and potently cytotoxic DNA interstrand cross-links in the minor groove of DNA. In particular, the development of PBD dimer SJG-136 (SG2000), currently in Phase II clinical trials, is presented. Potential future cancer therapeutic applications of PBDs, including their use as components of targeting strategies, are also discussed. The culmination of over four decades of study on structure-activity relationships of PBDs has led to a detailed understanding of how to introduce structural modification to enhance biological activity and potency. The challenge for the next phase in the development of the PBDs is to harness this activity and potency in a new generation of cancer ...Continue Reading


Mar 7, 1991·Nucleic Acids Research·J D FarmerJ W Suggs
Aug 1, 1974·Journal of the National Cancer Institute·C CargillG Zbinden
Dec 20, 1965·Journal of the American Chemical Society·W LeimgruberJ Berger
Sep 1, 1965·The Journal of New Drugs·S Korman, M D Tendler
Jan 31, 1995·Biochemistry·S M Rink, P B Hopkins
Aug 17, 1996·Mutation Research·P D Lawley, D H Phillips
Jul 18, 2001·Journal of the American Chemical Society·Q ZhouL H Hurley
Mar 22, 2002·The Lancet Oncology·P J McHughJ A Hartley
Aug 29, 2002·Chemical Communications : Chem Comm·Nectaroula CooperDavid E Thurston
May 16, 2003·Journal of Medicinal Chemistry·Moana TercelWilliam A Denny
Jun 5, 2003·Nature Biotechnology·Svetlana O DoroninaPeter D Senter
Sep 25, 2003·Bioorganic & Medicinal Chemistry Letters·Ahmed KamalP Praveen Kumar
Jul 1, 2004·Bioorganic & Medicinal Chemistry Letters·Ahmed KamalP Praveen Kumar
Aug 25, 2004·Bioorganic & Medicinal Chemistry Letters·Ahmed KamalP Praveen Kumar
May 30, 2006·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Sarah A BuhrowMatthew M Ames
Dec 13, 2006·Cancer Immunology, Immunotherapy : CII·John F DijosephNitin K Damle
May 29, 2007·Chemical Research in Toxicology·Wan-Ping HuJeh-Jeng Wang
Sep 8, 2007·Bioorganic & Medicinal Chemistry·Ahmed KamalSurekha M Zingde

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Oct 17, 2015·International Journal of Molecular Sciences·Feng JiangGe Zhang
Feb 2, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·George Varvounis
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Apr 17, 2012·Current Opinion in Pharmacology·John A Hartley, Daniel Hochhauser
Mar 11, 2016·Current Opinion in Immunology·Bart Ecg de Goeij, John M Lambert
Dec 21, 2012·Chemical Biology & Drug Design·John A FlygarePaul Aristoff
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Aug 1, 2015·Bioanalysis·L Nathan TumeyXiaogang Han
Apr 22, 2014·Bioorganic Chemistry·Albert Bolhuis, Janice R Aldrich-Wright
Nov 19, 2013·Drug Discovery Today·Heidi L PerezRobert M Borzilleri
Dec 6, 2014·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·LeeRon Shefet-Carasso, Itai Benhar
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Oct 16, 2016·Protein & Cell·Kyoji Tsuchikama, Zhiqiang An
Aug 19, 2014·PloS One·Khondaker M RahmanDavid E Thurston
Aug 12, 2014·Organic & Biomolecular Chemistry·Felix F SchumacherStephen Caddick
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Oct 5, 2017·Angewandte Chemie·Elisabeth DornischEllen L Zechner
Mar 13, 2019·Journal of the National Cancer Institute·Michael J BirrerRichard C Bates
Jun 20, 2019·Journal of Cellular Physiology·Sajad YaghoubiMeghdad Abdollahpour-Alitappeh
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