Inhibitors of steroidal cytochrome p450 enzymes as targets for drug development

Dutasteride, however, is a so-called dual inhibitor with both 5α-R1 and 5α-R2 inhibition. IC50 for 5α-R1 is 7 nM but 6 nM for 5α-R2. As mentioned above, it reduces DHT > 90% overall, or precisely % and for intraprostatic DHT the reduction is 97-99%. Dutasteride has also been found to inhibit 5α-R3, in vitro, with IC50= nM. [18] The 2,5-difluorophenyl side chain on the D-ring of the compound shows significant lipophilic features and as increased lipophilicity enhances the potency of the compounds binding at pocket site, its potency is much greater than of finasteride. [25]

Research suggests the common table mushroom has anti- aromatase [17] properties and therefore possible anti-estrogen activity. In 2009, a case-control study of the eating habits of 2,018 women in southeast China revealed that women who consumed greater than 10 grams of fresh mushrooms or greater than 4 grams of dried mushrooms per day had an approximately 50% lower incidence of breast cancer. Chinese women who consumed mushrooms and green tea had a 90% lower incidence of breast cancer. [18] However the study was relatively small (2,018 patients participating) and limited to Chinese women of southeast China.

It may be that the greatest risk of inducing a myocardial infarction is in a patient with undiagnosed coronary vascular disease. Before COX-2 selective inhibitors became available, this patient may have been prescribed another NSAID. This would have had an aspirin-like antiplatelet effect and, if anything, might have been expected to reduce the risk of infarction. If the patient is instead commenced on a COX-2 selective inhibitor the balance swings towards a prothrombotic state that theoretically might result in an infarction. This theoretical point is supported by the results of the VIGOR study and the termination of the APPROVe study because of an excess risk of myocardial infarction and stroke in patients taking rofecoxib for 18 months.

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  • Citation tools Download this article to citation manager Trelle Sven , Reichenbach Stephan , Wandel Simon , Hildebrand Pius , Tschannen Beatrice , Villiger Peter M et al. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis BMJ 2011; 342 :c7086
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    Inhibitors of steroidal cytochrome p450 enzymes as targets for drug development

    inhibitors of steroidal cytochrome p450 enzymes as targets for drug development

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  • Citation tools Download this article to citation manager Trelle Sven , Reichenbach Stephan , Wandel Simon , Hildebrand Pius , Tschannen Beatrice , Villiger Peter M et al. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis BMJ 2011; 342 :c7086
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