SJG-136 (NSC 694501), a novel rationally designed DNA minor groove interstrand cross-linking agent with potent and broad spectrum antitumor activity: part 1: cellular pharmacology, in vitro and initial in vivo antitumor activity

Cancer Research
John A HartleyDavid E Thurston

Abstract

SJG-136 (NSC 694501) is a rationally designed pyrrolobenzodiazepine dimer that binds in the minor groove of DNA. It spans 6 bp with a preference for binding to purine-GATC-pyrimidine sequences. The agent has potent activity in the National Cancer Institute (NCI) anticancer drug screen with 50% net growth inhibition conferred by 0.14 to 320 nmol/L (7.4 nmol/L mean). Sensitive cell lines exhibit total growth inhibition and 50% lethality after treatment with as little as 0.83 and 7.1 nmol/L SJG-136, respectively. COMPARE and molecular target analysis of SJG-136 data versus that of >60,000 compounds tested in the NCI 60 cell line screen shows that, although the agent has similarity to other DNA binding agents, the pattern of activity for SJG-136 does not fit within the clusters of any known agents, suggesting that SJG-136 possesses a distinct mechanism of action. Testing in the NCI standard hollow fiber assay produced prominent growth inhibition in 20 of 24 i.p. and 7 of 24 s.c. test combinations with 5 of 12 cell lines exhibiting cell kill. In addition, SJG-136 produced antitumor activity in mice bearing CH1 and CH1cisR xenografts, a cisplatin-resistant human ovarian tumor model, and also in mice bearing LS174T xenografts, a human...Continue Reading

References

Jun 5, 1991·Journal of the National Cancer Institute·A MonksA Vaigro-Wolff
Nov 15, 2000·British Journal of Cancer·E A Sausville, J I Johnson
Nov 15, 1996·The Journal of Organic Chemistry·David E. ThurstonLaurence H. Hurley
Mar 22, 2002·The Lancet Oncology·P J McHughJ A Hartley
Apr 19, 2003·Annals of Oncology : Official Journal of the European Society for Medical Oncology·G H SchwartzE K Rowinsky

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Citations

Aug 13, 2009·Cancer Chemotherapy and Pharmacology·Yelena Y JanjigianNaiyer A Rizvi
Dec 29, 2010·Cancer Chemotherapy and Pharmacology·Joel M ReidMatthew M Ames
Mar 7, 2012·ACS Chemical Biology·Isaac T YonemotoBarbara Gerratana
Dec 21, 2010·Chemical Reviews·Dyeison Antonow, David E Thurston
Jan 24, 2009·Journal of Natural Products·Qiuwen MiSteven M Swanson
Apr 2, 2005·Nature Reviews. Cancer·Stephen Neidle, David E Thurston
May 14, 2009·Chemical Communications : Chem Comm·Khondaker M Rahman, David E Thurston
May 2, 2012·The Journal of Antimicrobial Chemotherapy·Khondaker M RahmanPeter W Taylor
Mar 24, 2011·Nucleic Acids Research·Khondaker M RahmanDavid E Thurston
Feb 25, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Igor PuzanovMace L Rothenberg
Apr 5, 2011·Expert Opinion on Investigational Drugs·John A Hartley
Nov 12, 2015·International Journal of Molecular Sciences·Gaëlle Savreux-LengletMarie-Hélène David-Cordonnier
Jun 15, 2010·Medicinal Research Reviews·Barbara Gerratana
Feb 20, 2015·Protein Science : a Publication of the Protein Society·Julien MarcouxSarah Cianférani
Jul 28, 2005·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·S M GuichardD I Jodrell
Aug 19, 2015·BMC Veterinary Research·Maria Mellinas-GomezJohn A Hartley
Dec 5, 2014·Molecular Pharmaceutics·John F Valliere-DouglassLucy Y Pan
Sep 17, 2014·European Journal of Medicinal Chemistry·Naoto KojimaMasayuki Yamashita
Aug 4, 2012·Journal of Photochemistry and Photobiology. B, Biology·Gul Shahzada KhanDavid Barker
May 21, 2013·Steroids·Mohamed ShaabanMohamed A Ghani
Feb 25, 2015·Pharmacology & Therapeutics·Deepak SampathPeter S Dragovich
Mar 29, 2014·Angewandte Chemie·Ravi V J ChariWayne C Widdison
Nov 20, 2016·Angewandte Chemie·Julia MantajDavid E Thurston
Jun 17, 2020·Expert Opinion on Biological Therapy·John A Hartley
Nov 22, 2015·Pharmacological Reviews·Paul Polakis

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