In vitro and in vivo models for the evaluation of potent inhibitors of male rat 17α-hydroxylase/C17,20-lyase

Determination of 17α-hydroxylase-C17,20-lyase (P45017α) enzyme activities and their inhibition by selected steroidal picolyl and picolinylidene compounds

“…iC 50 parameters of references ketoconazole and abiraterone were found 1.86 ± 0.25 μM and 0.034 ± 0.003 µM for 17α-hydroxylase, and 0.32 ± 0.02 µM and 0.0125 ± 0.0015 µM for C 17,20 -lyase in our P450 17α inhibition test, respectively. these reference results are in good agreement with values found in the literature [4,9,15,18,23,[31][32]34]. Table 1 In vitro inhibition of 17α-hydroxylase and C 17,20 -lyase activities of the rat testicular P450 …”

“…Further incubation techniques apply non-labelled substrate steroids. enzyme products in these methods can be either isolated by high performance liquid chromatography and detected by ultraviolet spectrophotometry [20,[34][35] or can be directly quantified by specific immunoassays [9]. Technologies based on quantification of radio-labelled steroidal enzyme products, nevertheless, are acknowledged superior to other methods in sense of both precision and qualitative identification.…”

Abiraterone Acetate (Zytiga®): An Inhibitor of CYP17 as a Therapeutic for Castration‐Resistant Prostate Cancer

“…Based on these observations and modelling efforts, the ICR group designed a series of steroidal structure-based analogues, bearing a pyridyl substituent at C-17, where, in the binding pocket, optimal proximity to the heme group of the P450 enzyme was predicted [16]. Thus, a first set of pregnenolone analogues (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24) was prepared varying the position of the pyridyl nitrogen (Table 6.1). The 4-pyridyl analogues (14) were poor inhibitors of CYP17 enzymes, whereas the 2-pyridyl (13) and 3-pyridyl (11) analogues were excellent inhibitors, the latter achieving single digit nanomolar (nM) IC 50 s (Table 6.1).…”

Biological and clinical effects of abiraterone on anti-resorptive and anabolic activity in bone microenvironment

“…Влияние AA на дифференцировку и активность пер-вичных ОКЛ при наличии или при отсутствии стероидов Первичные клетки обрабатывали АА в 2 различ-ных концентрациях -5 и 10 мкмоль / л, как и в дру-гих доклинических исследованиях in vitro, в рамках которых концентрация величиной 10 мкмоль / л бы-ла максимальной [13][14][15]. Ни одна из доз не влияла на жизнеспособность ОКЛ.…”