Activity profile of the novel aziridinylbenzoquinones MeDZQ and RH1 in human tumour xenografts.

Abstract

BACKGROUND:

RH1 and MeDZQ represent novel aziridinylbenzoquinones that can be activated by DT-diaphorase to form unique DNA lesions. RH1 is due to enter a phase 1 clinical trial in the United Kingdom in the summer of 2003, where pharmacodynamic monitoring of DT-diaphorase will be performed.

MATERIALS AND METHODS:

The antitumour efficacy of RH1 and MeDZQ has been studied in 4 human xenografts (3 non-small cell lung cancer and 1 colon cancer), and compared to the level of constitutive DT-Diaphorase activity measured by the DCPIP assay.

RESULTS:

The 4 xenografts exhibited a wide range of DT-diaphorase activity (4.8-303 nmol/min/mg). Greater antitumour activity was recorded in the xenografts expressing high levels of DT-diaphorase (e.g. NX002, DT-diaphorase activity, 303 +/- 52 nmol/min/mg, T/C to MeDZQ, 33.3% and to RH1, 43.4%).

CONCLUSION:

These data add in vivo support to a role for DT-Diaphorase in the antitumour activity of RH1.

• Authors: Jeffrey Cummings, Alison Ritchie, John Butler, Timothy H Ward, Simon Langdon
• Journal: Anticancer research (Anticancer Res) 2003 Sep-Oct Vol. 23 Issue 5A Pg. 3979-83 ISSN: 0250-7005 [Print] Greece
• PMID: 14666706 (Publication Type: Journal Article)

Chemical References

• 2,5-diaziridinyl-3-(hydroxymethyl)-6-methyl-1,4-benzoquinone
• Antineoplastic Agents
• Aziridines
• Benzoquinones
• 2,5-dimethyl-3,6-diaziridinyl-1,4-benzoquinone
• NAD(P)H Dehydrogenase (Quinone)

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Aziridines (pharmacology)
• Benzoquinones (pharmacology)
• Carcinoma, Non-Small-Cell Lung (drug therapy, enzymology)
• Colonic Neoplasms (drug therapy, enzymology)
• Dose-Response Relationship, Drug
• Female
• Humans
• Lung Neoplasms (drug therapy, enzymology)
• Mice
• Mice, Nude
• NAD(P)H Dehydrogenase (Quinone) (metabolism)
• Transplantation, Heterologous
• Xenograft Model Antitumor Assays