Activity profile of the novel aziridinylbenzoquinones MeDZQ and RH1 in human tumour xenografts
Cummings, J.; Ritchie, A.; Butler, J.; Ward, T.H.; Langdon, S.
Anticancer Research 23(5a): 3979-3983
2003
ISSN/ISBN: 0250-7005 PMID: 14666706 Document Number: 562152
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 I 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.