20-Amino and 20,21-aziridinyl pregnene steroids: Development of potent inhibitors of 17α-hydroxylase/C17,20-lyase (P450 17)

Njar, Vincent C.O.; Hector, Markus; Hartmann, Rolf W.

doi:10.1016/0968-0896(96)00138-1

Cited by 45 publications

(36 citation statements)

References 23 publications

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“…However, the decline in adrenal androgen levels was not associated with decreased PSA levels or CaP regression 26-28. Ketoconazole's lack of enzyme specificity, drug toxicities, patient side effects and the need for steroid supplementation warranted development of a more specific adrenal androgen synthesis inhibitor 29-31. Although ketoconazole was identified as a better adrenal androgen synthesis inhibitor than aminoglutethimide, clinical interest for adrenal androgen inhibition remained low until adrenal androgens were shown to clearly be involved in DHT synthesis.…”

Section: Orchiectomy Adrenalectomy and Early Adrenal Androgen Inhibimentioning

confidence: 99%

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Roles for the Backdoor Pathway of Androgen Metabolism in Prostate Cancer Response to Castration and Drug Treatment

Fiandalo¹,

Wilton²,

Mohler³

2014

Int. J. Biol. Sci.

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Almost all men who present with advanced prostate cancer (CaP) and many men who fail potentially curative therapy are treated with androgen deprivation therapy (ADT). ADT is not curative and CaP recurs as the lethal phenotype. The goal of this review is to describe the evolution of adrenal androgen blockade, how new androgen measurement methods have furthered understanding of androgen metabolism, and how further understanding of the backdoor pathway of androgen metabolism may lead to interventions that extend survival even more.

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Section: Orchiectomy Adrenalectomy and Early Adrenal Androgen Inhibimentioning

confidence: 99%

“…One potent inhibitor against CYP17A1 is the new FDA-approved drug, abiraterone 31, 45-48. Abiraterone was investigated first in men with castration-recurrent, metastatic CaP who had failed chemotherapy 49 in whom extension of survival averaged 4 months 50.…”

Section: Mass Spectrometry Abiraterone and The Backdoor Pathway Of Amentioning

confidence: 99%

Roles for the Backdoor Pathway of Androgen Metabolism in Prostate Cancer Response to Castration and Drug Treatment

Fiandalo¹,

Wilton²,

Mohler³

2014

Int. J. Biol. Sci.

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“…A difference in the inhibitory potential of rat CYP17 of the aziridinylpregnanes 78-81 was observed between the S-and R-isomers, the S-isomers 78 and 80 being 162 and 30-fold more potent than the R-isomers, respectively (Fig. 7, Table 3, entries 12-15) [115]. However, this finding was not corroborated by later studies that used the human enzyme [116].…”

Section: Pregnanesmentioning

confidence: 87%

Steroidal CYP17 Inhibitors for Prostate Cancer Treatment: From Concept to Clinic

Salvador¹,

Moreira

Silvestre³

2013

Advances in Prostate Cancer

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“…7) were shown to be powerful inhibitors of rat testicular CYP17, showing better inhibition than ketoconazole (2) ( Table 9, entries 12-15) [250]. The inhibition was markedly enantioselective, as the S-isomers 177 and 179 were 162 and 30-fold more potent than the R-isomers 178 and 180, respectively.…”

Section: Pregnane Derivativesmentioning

confidence: 97%

CYP17 Inhibitors for Prostate Cancer Treatment – An Update

Moreira

Salvador²,

Vasaitis³

et al. 2008

CMC

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It is almost 70 years since the discovery by Huggins et al. that androgens are essential for prostate cancer (PC) growth and progression, and there has been about 30 years experience using ketoconazole for PC therapy. Since then we have come a long way in learning about the disease and developing new strategies to approach it, among which is cytochrome 17alpha-hydroxylase-C(17,20)-lyase (CYP17) inhibition. This review focuses on the efforts to find prospective CYP17 inhibitors, both steroidal and nonsteroidal, in the absence of a 3D structure of the enzyme. It covers almost 4 decades of literature with highlights on the most significant achievements in this area, providing insight into PC pathophysiology, management and treatment options.

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20-Amino and 20,21-aziridinyl pregnene steroids: Development of potent inhibitors of 17α-hydroxylase/C17,20-lyase (P450 17)

Cited by 45 publications

References 23 publications

Roles for the Backdoor Pathway of Androgen Metabolism in Prostate Cancer Response to Castration and Drug Treatment

Roles for the Backdoor Pathway of Androgen Metabolism in Prostate Cancer Response to Castration and Drug Treatment

Steroidal CYP17 Inhibitors for Prostate Cancer Treatment: From Concept to Clinic

CYP17 Inhibitors for Prostate Cancer Treatment – An Update

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