Isopropylidene substitution increases activity and selectivity of biphenylmethylene 4-pyridine type CYP17 inhibitors.

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Hu Q, Yin L, Jagusch C, Hille UE, Hartmann RW

Isopropylidene substitution increases activity and selectivity of biphenylmethylene 4-pyridine type CYP17 inhibitors.

J Med Chem. 2010 Jul 8;53(13):5049-53. doi: 10.1021/jm100400a.

PubMed ID

20550118 [ View in PubMed

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Abstract

CYP17 inhibition is a promising therapy for prostate cancer (PC) because proliferation of 80% of PC depends on androgen stimulation. Introduction of isopropylidene substituents onto the linker of biphenylmethylene 4-pyridines resulted in several strong CYP17 inhibitors, which were more potent and selective, regarding CYP 11B1, 11B2, 19 and 3A4, than the drug candidate abiraterone.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Abiraterone	Cytochrome P450 3A4	IC 50 (nM)	2700	N/A	N/A	Details
Abiraterone	Steroid 17-alpha-hydroxylase/17,20 lyase	IC 50 (nM)	72	N/A	N/A	Details
Ketoconazole	Cytochrome P450 11B1, mitochondrial	IC 50 (nM)	127	N/A	N/A	Details