The renaissance of polypharmacology in the development of anti-cancer therapeutics: Inhibition of the "Triad of Death" in cancer by Di-2-pyridylketone thiosemicarbazones

Pharmacological Research : the Official Journal of the Italian Pharmacological Society
Patric J JanssonDes R Richardson

Abstract

Cancer is a disease that is a "moving target", since as the condition progresses, the molecular targets change and evolve. Moreover, due to clonal selection, a specific anti-cancer drug with one molecular target may only be effective for a limited time period before drug resistance results and the agent becomes ineffective. Hence, the concept of an anti-tumor therapeutic exhibiting polypharmacology can be highly advantageous, rather than a therapeutic obstacle. A novel class of agents possessing these desirable properties are the di-2-pyridylketone thiosemicarbazones, which bind iron and copper to affect a variety of critical molecular targets in tumors. In fact, these compounds possess multiple properties that enable them to overcome the "triad of death" in cancer, namely: primary tumor growth, drug resistance and metastasis. In fact, at the molecular level, their potent anti-oncogenic activity includes: up-regulation of the metastasis suppressor, N-myc downstream regulated gene 1; up-regulation of the tumor suppressor, PTEN; down-regulation of the proto-oncogene, cyclin D1; inhibition of the rate-limiting step in DNA synthesis catalyzed by ribonucleotide reductase; and the inhibition of multiple oncogenic signaling pathways, ...Continue Reading

References

Apr 8, 2003·Current Medicinal Chemistry·Joan L BussSuzy V Torti
Jun 27, 2003·American Journal of Hematology·Timothy B Chaston, Des R Richardson
Oct 8, 2003·The Oncologist·Gregory D LeonardSusan E Bates
Jun 9, 2004·Oncogene·Sucharita BandyopadhyayKounosuke Watabe
May 4, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Manish A ShahGary K Schwartz
Dec 31, 2005·Pharmacological Reviews·Danuta S Kalinowski, Des R Richardson
Aug 22, 2006·Carcinogenesis·Zaklina Kovacevic, Des R Richardson
Feb 9, 2008·Histochemistry and Cell Biology·Tino KurzUlf T Brunk
Jun 28, 2008·Biochimica Et Biophysica Acta·Zaklina KovacevicDes R Richardson
Sep 9, 2008·Cancer Treatment Reviews·Anshul Gupte, Russell J Mumper
Oct 22, 2008·Nature Chemical Biology·Andrew L Hopkins
Nov 14, 2008·Cancer Letters·Katsuya TsuchiharaHiroyasu Esumi
Jan 14, 2009·American Journal of Hematology·Egarit NoulsriKovit Pattanapanyasat
Dec 1, 2009·Current Opinion in Cell Biology·Candia M KenificJayanta Debnath
Aug 20, 2010·Journal of Inorganic Biochemistry·Patric J JanssonDes R Richardson
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
Sep 1, 2009·Future Medicinal Chemistry·Danuta S KalinowskiDes R Richardson
Aug 26, 2011·Drug Discovery Today·Giovanni BottegoniAndrea Cavalli
Mar 20, 2012·Antioxidants & Redox Signaling·Angelica M MerlotDes R Richardson
Nov 28, 2012·Proteomics. Clinical Applications·Sonja Hess
Jan 1, 2013·Expert Review of Clinical Pharmacology·A Srinivas Reddy, Shuxing Zhang
Mar 26, 2013·Drug Discovery Today·Ye Hu, Jürgen Bajorath
Jun 12, 2013·Journal of Clinical Pathology·Dong-Hun BaeDes R Richardson
Aug 8, 2013·Journal of Medicinal Chemistry·Jens-Uwe Peters

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Citations

Feb 5, 2016·Biochimica Et Biophysica Acta·Danuta S KalinowskiDes R Richardson
Feb 5, 2016·Biochimica Et Biophysica Acta·Jasmina PaluncicDes R Richardson
Jan 15, 2017·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Sumit SahniDes R Richardson
Mar 9, 2017·Dalton Transactions : an International Journal of Inorganic Chemistry·Angela SîrbuVladimir B Arion
Feb 25, 2018·Analytical and Bioanalytical Chemistry·Karla PelivanChristian R Kowol
Jan 18, 2018·Antioxidants & Redox Signaling·Petra HeffeterChristian R Kowol
Sep 1, 2018·Briefings in Bioinformatics·Misagh NaderiMichal Brylinski
Feb 6, 2019·Chemistry : a European Journal·Thomas FischerRainer Riedl
Jul 8, 2017·Current Medicinal Chemistry·Angelica M MerlotDes R Richardson
Apr 11, 2020·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Fatemeh Ghorbani ParsaMajid Mahdavi
May 1, 2018·Oncotarget·Katarzyna MalarzRobert Musiol
Mar 2, 2016·Aging·Zaklina KovacevicDes R Richardson
Jun 24, 2016·Metallomics : Integrated Biometal Science·Kyung Chan ParkDes R Richardson
Dec 29, 2019·Pharmaceuticals·Carmela BonaccorsoDiego La Mendola
Jul 28, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Syer C LimZaklina Kovacevic
Sep 11, 2020·Chembiochem : a European Journal of Chemical Biology·Alexander HaseloerAxel Klein
Jan 24, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Bekesho GeletaZaklina Kovacevic
Sep 21, 2020·Biochimica Et Biophysica Acta. Molecular Basis of Disease·S KrishanD R Richardson
Jan 7, 2020·Biochimica Et Biophysica Acta. Molecular Basis of Disease·S KrishanD R Richardson
Nov 14, 2020·Dalton Transactions : an International Journal of Inorganic Chemistry·Éva A EnyedyChristian R Kowol
Aug 9, 2020·Hematology/oncology and Stem Cell Therapy·Íris Mattos Santos-PirathMaria Cláudia Santos-Silva
Jun 12, 2020·Biochimica Et Biophysica Acta. General Subjects·Kyung Chan Park, Des R Richardson

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