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Influence of phosphate and phosphoesters on the decomposition pathway of 1,2-bis(methylsulfonyl)-1-(2-chloroethyhydrazine (90CE), the active anticancer moiety generated by Laromustine, KS119, and KS119W.

Penketh PG, Shyam K, Zhu R, Baumann RP, Ishiguro K, Sartorelli AC.

Chem Res Toxicol. 2014 May 19;27(5):818-33. doi: 10.1021/tx500004y. Epub 2014 Mar 24.


Influence of glutathione and glutathione S-transferases on DNA interstrand cross-link formation by 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)hydrazine, the active anticancer moiety generated by laromustine.

Penketh PG, Patridge E, Shyam K, Baumann RP, Zhu R, Ishiguro K, Sartorelli AC.

Chem Res Toxicol. 2014 Aug 18;27(8):1440-9. doi: 10.1021/tx500197t. Epub 2014 Jul 17.


Mode of action of the chloroethylating and carbamoylating moieties of the prodrug cloretazine.

Ishiguro K, Seow HA, Penketh PG, Shyam K, Sartorelli AC.

Mol Cancer Ther. 2006 Apr;5(4):969-76.


1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-[[1-(4-nitrophenyl)ethoxy]carbonyl]hydrazine: an anticancer agent targeting hypoxic cells.

Seow HA, Penketh PG, Shyam K, Rockwell S, Sartorelli AC.

Proc Natl Acad Sci U S A. 2005 Jun 28;102(26):9282-7. Epub 2005 Jun 17.


Carbamoylating activity associated with the activation of the antitumor agent laromustine inhibits angiogenesis by inducing ASK1-dependent endothelial cell death.

Ji W, Yang M, Praggastis A, Li Y, Zhou HJ, He Y, Ghazvinian R, Cincotta DJ, Rice KP, Min W.

PLoS One. 2014 Jul 28;9(7):e103224. doi: 10.1371/journal.pone.0103224. eCollection 2014.


Chloroethylating and methylating dual function antineoplastic agents display superior cytotoxicity against repair proficient tumor cells.

Zhu R, Baumann RP, Patridge E, Penketh PG, Shyam K, Ishiguro K, Sartorelli AC.

Bioorg Med Chem Lett. 2013 Mar 15;23(6):1853-9. doi: 10.1016/j.bmcl.2013.01.016. Epub 2013 Jan 11.


Role of O6-alkylguanine-DNA alkyltransferase in the cytotoxic activity of cloretazine.

Ishiguro K, Shyam K, Penketh PG, Sartorelli AC.

Mol Cancer Ther. 2005 Nov;4(11):1755-63.


Quantitative relationship between guanine O(6)-alkyl lesions produced by Onrigin™ and tumor resistance by O(6)-alkylguanine-DNA alkyltransferase.

Ishiguro K, Zhu YL, Shyam K, Penketh PG, Baumann RP, Sartorelli AC.

Biochem Pharmacol. 2010 Nov 1;80(9):1317-25. doi: 10.1016/j.bcp.2010.07.022. Epub 2010 Jul 21.


KS900: A hypoxia-directed, reductively activated methylating antitumor prodrug that selectively ablates O(6)-alkylguanine-DNA alkyltransferase in neoplastic cells.

Baumann RP, Ishiguro K, Penketh PG, Shyam K, Zhu R, Sartorelli AC.

Biochem Pharmacol. 2011 May 15;81(10):1201-10. doi: 10.1016/j.bcp.2011.02.019. Epub 2011 Mar 17.


1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-[[1-(4-nitrophenyl)ethoxy]carbonyl]hydrazine (KS119): a cytotoxic prodrug with two stable conformations differing in biological and physical properties.

Penketh PG, Baumann RP, Shyam K, Williamson HS, Ishiguro K, Zhu R, Eriksson ES, Eriksson LA, Sartorelli AC.

Chem Biol Drug Des. 2011 Oct;78(4):513-26. doi: 10.1111/j.1747-0285.2011.01193.x. Epub 2011 Sep 6.


1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-[(methylamino)carbonyl]hydrazine (VNP40101M): II. Role of O6-alkylguanine-DNA alkyltransferase in cytotoxicity.

Baumann RP, Shyam K, Penketh PG, Remack JS, Brent TP, Sartorelli AC.

Cancer Chemother Pharmacol. 2004 Apr;53(4):288-95. Epub 2003 Dec 17.


1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-[(methylamino)carbonyl]hydrazine (VNP40101M): I. Direct inhibition of O6-alkylguanine-DNA alkyltransferase (AGT) by electrophilic species generated by decomposition.

Penketh PG, Shyam K, Baumann RP, Remack JS, Brent TP, Sartorelli AC.

Cancer Chemother Pharmacol. 2004 Apr;53(4):279-87. Epub 2003 Dec 24.


Hydrogen peroxide inducible DNA cross-linking agents: targeted anticancer prodrugs.

Kuang Y, Balakrishnan K, Gandhi V, Peng X.

J Am Chem Soc. 2011 Dec 7;133(48):19278-81. doi: 10.1021/ja2073824. Epub 2011 Nov 10.


Differential inhibition of cellular glutathione reductase activity by isocyanates generated from the antitumor prodrugs Cloretazine and BCNU.

Rice KP, Penketh PG, Shyam K, Sartorelli AC.

Biochem Pharmacol. 2005 May 15;69(10):1463-72.


Lethality to leukemia cell lines of DNA interstrand cross-links generated by Cloretazine derived alkylating species.

Penketh PG, Baumann RP, Ishiguro K, Shyam K, Seow HA, Sartorelli AC.

Leuk Res. 2008 Oct;32(10):1546-53. doi: 10.1016/j.leukres.2008.03.005. Epub 2008 May 13.


Preliminary studies with a new hypoxia-selective cytotoxin, KS119W, in vitro and in vivo.

Kim EY, Liu Y, Akintujoye OM, Shyam K, Grove TA, Sartorelli AC, Rockwell S.

Radiat Res. 2012 Sep;178(3):126-37. Epub 2012 Aug 3.

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