Which enzyme is inhibited by Orteronel?
['PURPOSE: Orteronel (TAK-700) is a non-steroidal, selective, reversible inhibitor of 17,20-lyase.', 'The drug orteronel selectively blocked the lyase reaction of P450 17A1 but only in the case of Prog. ', 'Preclinical assessment of Orteronel(®), a CYP17A1 enzyme inhibitor in rats.', 'Orteronel (TAK-700) is a novel and selective inhibitor of CYP17A1, which is expressed in testicular, adrenal and prostate tumor tissues.', 'Orteronel is a nonsteroidal, selective inhibitor of 17,20-lyase that was recently in phase 3 clinical development as a treatment for castration-resistant prostate cancer. ', 'Human liver microsomal studies indicated that orteronel weakly inhibits CYP1A2, 2C8, 2C9 and 2C19, with IC50 values of 17.8, 27.7, 30.8 and 38.8 µm, respectively, whereas orteronel does not inhibit CYP2B6, 2D6 or 3A4/5 (IC50 \u2009>\u2009100 µm).', 'PURPOSE: Orteronel (TAK-700) is an investigational, nonsteroidal, oral, inhibitor of androgen synthesis with greater specificity for 17,20-lyase than for 17α-hydroxylase.', 'Based on these observations, potent agents targeting the AR axis were developed: 1) inhibitors of CYP17 (a key enzyme in the production of androgens), such as abiraterone and orteronel; 2) AR antagonists that bind to AR and impair AR activation, such as enzalutamide and ARN-509. ', 'Orteronel inhibits the 17,20 lyase activity of the enzyme CYP17A1, which is important for androgen synthesis in the testes, adrenal glands and prostate cancer cells. ', 'Inhibition of 17α-hydroxylase by abiraterone results in accumulation of upstream mineralocorticoids due to loss of cortisol-mediated suppression of pituitary adrenocorticotropic hormone (ACTH), providing a rationale for development of CYP17 inhibitors with increased specificity for 17,20-lyase (orteronel, galeterone and VT-464) that can potentially be administered without exogenous corticosteroids.', 'Phase I/II trial of orteronel (TAK-700)--an investigational 17,20-lyase inhibitor--in patients with metastatic castration-resistant prostate cancer.', 'Orteronel (TAK-700) is an investigational, oral, nonsteroidal, selective, reversible inhibitor of 17,20-lyase, a key enzyme in the production of androgenic hormones. ', 'Hence, some molecules target the androgen biosynthesis, as abiraterone acetate and orteronel, which are selective inhibitors of the enzyme CYP17.', 'To achieve enhanced clinical benefits, new strategies are being explored that include selective inhibition of the C17,20-lyase activity of CYP17 and multi-targeting strategies that affect androgen synthesis and signalling at different points. Some of these strategies-including the drugs orteronel, VT-464 and galeterone--are supported by preclinical data and are being explored in the clinic.', 'Besides further CYP17 inhibitors (Orteronel, Galeterone, VT-464 and CFG920), androgen receptor antagonists (ARN-509, ODM-201, AZD-3514 and EZN-4176) and vaccine Prostvac, more drug candidates with various mechanisms or new indications of launched drugs are currently under evaluation in different stages of clinical trials, including various kinase inhibitors and platinum complexes. ', 'Effect of an investigational CYP17A1 inhibitor, orteronel (TAK-700), on estrogen- and corticoid-synthesis pathways in hypophysectomized female rats and on the serum estradiol levels in female cynomolgus monkeys.', 'Orteronel (TAK-700) is an investigational, non-steroidal inhibitor of CYP17A1 with preferential inhibition of 17,20-lyase in NCI-H295 cells. ', 'In summary, orteronel can suppress serum estradiol concentrations in hypophysectomized female rats and monkeys through selective inhibition of CYP17A1 activity, suggesting that orteronel might be effective for hormone-dependent breast cancers and estrogen-dependent diseases.', 'Development and validation of an RP-HPLC method for the quantitation of Orteronel (TAK-700), a CYP17A1 enzyme inhibitor, in rat plasma and its application to a pharmacokinetic study.', 'Targeting the adrenal gland in castration-resistant prostate cancer: a case for orteronel, a selective CYP-17 17,20-lyase inhibitor.', 'A new CYP17 inhibitor, with more selective inhibition of 17,20-lyase over 17α-hydroxylase, orteronel (TAK-700), is currently undergoing phase III clinical trials in pre- and postchemotherapy CRPC. ', 'Effect of a novel 17,20-lyase inhibitor, orteronel (TAK-700), on androgen synthesis in male rats.', 'Orteronel (TAK-700), 6-[(7S)-7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl]-N-methyl-2-naphthamide, is a novel, non-steroidal, selective inhibitor of the 17,20-lyase activity of CYP17A--a key enzyme in the production of steroidal hormones--and is being developed as a therapy for PC. ', 'Orteronel inhibited 17,20-lyase activity in rats with an IC(50) of 1200 nM but did not inhibit 17α-hydroxylase or 11β-hydroxylase (CYP11B1) activity in rats at concentrations up to 10 μM.', 'Orteronel (TAK-700), a novel non-steroidal 17,20-lyase inhibitor: effects on steroid synthesis in human and monkey adrenal cells and serum steroid levels in cynomolgus monkeys.', 'Orteronel (TAK-700), a novel, selective, and potent inhibitor of 17,20-lyase is under development as a drug to inhibit androgen synthesis. In this study, we quantified the inhibitory activity and specificity of orteronel for testicular and adrenal androgen production by evaluating its effects on CYP17A1 enzymatic activity, steroid production in monkey adrenal cells and human adrenal tumor cells, and serum levels of dehydroepiandrosterone (DHEA), cortisol, and testosterone after oral dosing in castrated and intact male cynomolgus monkeys.', ' In summary, orteronel potently inhibited the 17,20-lyase activity of monkey and human CYP17A1 and reduced serum androgen levels in vivo in monkeys. ', 'Discovery of orteronel (TAK-700), a naphthylmethylimidazole derivative, as a highly selective 17,20-lyase inhibitor with potential utility in the treatment of prostate cancer.', 'Orteronel (TAK-700), 6-[(7S)-7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl]-N-methyl-2-naphthamide, is a novel, non-steroidal, selective inhibitor of the 17,20-lyase activity of CYP17A--a key enzyme in the production of steroidal hormones--and is being developed as a therapy for PC. The purpose of this study was to elucidate the inhibitory activity of orteronel, in particular its specificity for androgen synthesis enzymes, in male rats--an androgen-synthesis model that largely reflects this pathway in humans.', 'In terms of human CYP17A1 and human adrenal tumor cells, orteronel inhibited 17,20-lyase activity 5.4 times more potently than 17-hydroxylase activity in cell-free enzyme assays and DHEA production 27 times more potently than cortisol production in human adrenal tumor cells, suggesting greater specificity of inhibition between 17,20-lyase and 17-hydroxylase activities in humans vs monkeys.', 'In summary, orteronel potently inhibited the 17,20-lyase activity of monkey and human CYP17A1 and reduced serum androgen levels in vivo in monkeys.', 'Orteronel (TAK-700) is a novel and selective inhibitor of CYP17A1, which is expressed in testicular, adrenal and prostate tumor tissues', 'Orteronel inhibits the 17,20 lyase activity of the enzyme CYP17A1, which is important for androgen synthesis in the testes, adrenal glands and prostate cancer cells', 'Orteronel (TAK-700), a novel, selective, and potent inhibitor of 17,20-lyase is under development as a drug to inhibit androgen synthesis', 'In summary, orteronel potently inhibited the 17,20-lyase activity of monkey and human CYP17A1 and reduced serum androgen levels in vivo in monkeys', 'Orteronel inhibited 17,20-lyase activity in rats with an IC(50) of 1200 nM but did not inhibit 17α-hydroxylase or 11β-hydroxylase (CYP11B1) activity in rats at concentrations up to 10 μM', 'In terms of human CYP17A1 and human adrenal tumor cells, orteronel inhibited 17,20-lyase activity 5.4 times more potently than 17-hydroxylase activity in cell-free enzyme assays and DHEA production 27 times more potently than cortisol production in human adrenal tumor cells, suggesting greater specificity of inhibition between 17,20-lyase and 17-hydroxylase activities in humans vs monkeys', 'In summary, orteronel can suppress serum estradiol concentrations in hypophysectomized female rats and monkeys through selective inhibition of CYP17A1 activity, suggesting that orteronel might be effective for hormone-dependent breast cancers and estrogen-dependent diseases', 'Hence, some molecules target the androgen biosynthesis, as abiraterone acetate and orteronel, which are selective inhibitors of the enzyme CYP17', 'Orteronel (TAK-700) is an investigational, oral, nonsteroidal, selective, reversible inhibitor of 17,20-lyase, a key enzyme in the production of androgenic hormones.']
['Orteronel inhibits the 17,20 lyase activity of the enzyme CYP17A1, which is important for androgen synthesis in the testes, adrenal glands and prostate cancer cells. Orteronel is used for treatment for castration-resistant prostate cancer.']
['CYP17A1']