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Antitumor activity of metal-chelating compound Dp44mT is mediated by formation of a redox-active copper complex that accumulates in lysosomes.

Lovejoy DB, Jansson PJ, Brunk UT, Wong J, Ponka P, Richardson DR.

Cancer Res. 2011 Sep 1;71(17):5871-80. doi: 10.1158/0008-5472.CAN-11-1218. Epub 2011 Jul 12.


The anticancer drug Dp44mT inhibits T-cell activation and CD25 through a copper-dependent mechanism.

Gundelach JH, Madhavan AA, Wettstein PJ, Bram RJ.

FASEB J. 2013 Feb;27(2):782-92. doi: 10.1096/fj.12-215756. Epub 2012 Nov 7.


Novel thiosemicarbazones of the ApT and DpT series and their copper complexes: identification of pronounced redox activity and characterization of their antitumor activity.

Jansson PJ, Sharpe PC, Bernhardt PV, Richardson DR.

J Med Chem. 2010 Aug 12;53(15):5759-69. doi: 10.1021/jm100561b.


Di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) overcomes multidrug resistance by a novel mechanism involving the hijacking of lysosomal P-glycoprotein (Pgp).

Jansson PJ, Yamagishi T, Arvind A, Seebacher N, Gutierrez E, Stacy A, Maleki S, Sharp D, Sahni S, Richardson DR.

J Biol Chem. 2015 Apr 10;290(15):9588-603. doi: 10.1074/jbc.M114.631283. Epub 2015 Feb 26.


Cellular uptake of the antitumor agent Dp44mT occurs via a carrier/receptor-mediated mechanism.

Merlot AM, Pantarat N, Menezes SV, Sahni S, Richardson DR, Kalinowski DS.

Mol Pharmacol. 2013 Dec;84(6):911-24. doi: 10.1124/mol.113.088393. Epub 2013 Oct 1.


Lysosomal membrane stability plays a major role in the cytotoxic activity of the anti-proliferative agent, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT).

Gutierrez EM, Seebacher NA, Arzuman L, Kovacevic Z, Lane DJ, Richardson V, Merlot AM, Lok H, Kalinowski DS, Sahni S, Jansson PJ, Richardson DR.

Biochim Biophys Acta. 2016 Jul;1863(7 Pt A):1665-81. doi: 10.1016/j.bbamcr.2016.04.017. Epub 2016 Apr 19.


The Anticancer Agent, Di-2-Pyridylketone 4,4-Dimethyl-3-Thiosemicarbazone (Dp44mT), Up-Regulates the AMPK-Dependent Energy Homeostasis Pathway in Cancer Cells.

Krishan S, Richardson DR, Sahni S.

Biochim Biophys Acta. 2016 Dec;1863(12):2916-2933. doi: 10.1016/j.bbamcr.2016.09.011. Epub 2016 Sep 15.


Complex forming competition and in-vitro toxicity studies on the applicability of di-2-pyridylketone-4,4,-dimethyl-3-thiosemicarbazone (Dp44mT) as a metal chelator.

Gaál A, Orgován G, Polgári Z, Réti A, Mihucz VG, Bősze S, Szoboszlai N, Streli C.

J Inorg Biochem. 2014 Jan;130:52-8. doi: 10.1016/j.jinorgbio.2013.09.016. Epub 2013 Oct 10.


A class of iron chelators with a wide spectrum of potent antitumor activity that overcomes resistance to chemotherapeutics.

Whitnall M, Howard J, Ponka P, Richardson DR.

Proc Natl Acad Sci U S A. 2006 Oct 3;103(40):14901-6. Epub 2006 Sep 26.


Antitumor activity and mechanism of action of the iron chelator, Dp44mT, against leukemic cells.

Noulsri E, Richardson DR, Lerdwana S, Fucharoen S, Yamagishi T, Kalinowski DS, Pattanapanyasat K.

Am J Hematol. 2009 Mar;84(3):170-6. doi: 10.1002/ajh.21350.


Methemoglobin formation by triapine, di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT), and other anticancer thiosemicarbazones: identification of novel thiosemicarbazones and therapeutics that prevent this effect.

Quach P, Gutierrez E, Basha MT, Kalinowski DS, Sharpe PC, Lovejoy DB, Bernhardt PV, Jansson PJ, Richardson DR.

Mol Pharmacol. 2012 Jul;82(1):105-14. doi: 10.1124/mol.112.078964. Epub 2012 Apr 16.


Novel second-generation di-2-pyridylketone thiosemicarbazones show synergism with standard chemotherapeutics and demonstrate potent activity against lung cancer xenografts after oral and intravenous administration in vivo.

Lovejoy DB, Sharp DM, Seebacher N, Obeidy P, Prichard T, Stefani C, Basha MT, Sharpe PC, Jansson PJ, Kalinowski DS, Bernhardt PV, Richardson DR.

J Med Chem. 2012 Aug 23;55(16):7230-44. doi: 10.1021/jm300768u. Epub 2012 Aug 3.


Structure-Activity Relationships of Di-2-pyridylketone, 2-Benzoylpyridine, and 2-Acetylpyridine Thiosemicarbazones for Overcoming Pgp-Mediated Drug Resistance.

Stacy AE, Palanimuthu D, Bernhardt PV, Kalinowski DS, Jansson PJ, Richardson DR.

J Med Chem. 2016 Sep 22;59(18):8601-20. doi: 10.1021/acs.jmedchem.6b01050. Epub 2016 Aug 30.


Design, synthesis, and characterization of novel iron chelators: structure-activity relationships of the 2-benzoylpyridine thiosemicarbazone series and their 3-nitrobenzoyl analogues as potent antitumor agents.

Kalinowski DS, Yu Y, Sharpe PC, Islam M, Liao YT, Lovejoy DB, Kumar N, Bernhardt PV, Richardson DR.

J Med Chem. 2007 Jul 26;50(15):3716-29. Epub 2007 Jun 30.


Novel di-2-pyridyl-derived iron chelators with marked and selective antitumor activity: in vitro and in vivo assessment.

Yuan J, Lovejoy DB, Richardson DR.

Blood. 2004 Sep 1;104(5):1450-8. Epub 2004 May 18.


Distinct mechanisms of cell-kill by triapine and its terminally dimethylated derivative Dp44mT due to a loss or gain of activity of their copper(II) complexes.

Ishiguro K, Lin ZP, Penketh PG, Shyam K, Zhu R, Baumann RP, Zhu YL, Sartorelli AC, Rutherford TJ, Ratner ES.

Biochem Pharmacol. 2014 Oct 1;91(3):312-22. doi: 10.1016/j.bcp.2014.08.006. Epub 2014 Aug 15.


Copper that cancer with lysosomal love!

Kovacevic Z, Sahni S, Richardson DR.

Aging (Albany NY). 2016 Feb;8(2):210-1. No abstract available.

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