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- W1967573722 abstract "Nitric oxide synthase (NOS) has been shown to be overexpressed in a number of human tumors compared to normal tissues and therefore potentially represents an exploitable target in future anticancer therapies. To achieve this, there will be a need to profile tumors to identify those expressing high levels of NOS; alternatively, endogenous (low) levels of NOS could be modulated by induction or through gene therapy approaches. NOS consists of a reductase domain which shares a high degree of sequence homology with P450 reductase and this domain supplies reducing equivalents to a haem containing oxygenase domain that is responsible for the production of nitric oxide. Thus, there are a number of routes of exploitation. Firstly, to take advantage of the reductase domain to activate bioreductive drugs as has been exemplified with tirapazamine and now extended to AQ4N (1,4-bis{2-(dimethylamino-N-oxide)ethylamino}5,8-dihydroxy-anthracene-9,10-dione). Secondly, to take advantage of nitric oxide production for its ability to increase the sensitivity of resistant hypoxic cells to radiation. Lastly, to utilize inhibition of HIF-1 to amplify NO based therapies. In this review we provide examples/evidence of how these objectives can be achieved." @default.
- W1967573722 created "2016-06-24" @default.
- W1967573722 creator A5011496653 @default.
- W1967573722 creator A5022370724 @default.
- W1967573722 creator A5030328910 @default.
- W1967573722 creator A5065281989 @default.
- W1967573722 date "2008-09-01" @default.
- W1967573722 modified "2023-10-10" @default.
- W1967573722 title "iNOS as a therapeutic target for treatment of human tumors" @default.
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