Proteins > Steroid 17-alpha-hydroxylase/17,20 lyase
Page last updated: 2024-08-07 15:39:00
Steroid 17-alpha-hydroxylase/17,20 lyase
A cytochrome P450 17A1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P05093]
Synonyms
EC 1.14.14.19;
17-alpha-hydroxyprogesterone aldolase;
1.14.14.32;
CYPXVII;
Cytochrome P450 17A1;
Cytochrome P450-C17;
Cytochrome P450c17;
Steroid 17-alpha-monooxygenase
Research
Bioassay Publications (45)
| Timeframe | Studies on this Protein(%) | All Drugs % |
|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 9 (20.00) | 18.2507 |
| 2000's | 13 (28.89) | 29.6817 |
| 2010's | 21 (46.67) | 24.3611 |
| 2020's | 2 (4.44) | 2.80 |
Compounds (23)
Drugs with Inhibition Measurements
Drugs with Activation Measurements
| Drug | Taxonomy | Measurement | Average (mM) | Bioassay(s) | Publication(s) |
|---|
| orteronel | Homo sapiens (human) | Kd | 0.0400 | 1 | 1 |
Synthesis, biological evaluation, and molecular modeling studies of methylene imidazole substituted biaryls as inhibitors of human 17alpha-hydroxylase-17,20-lyase (CYP17)--part II: Core rigidification and influence of substituents at the methylene bridge.Bioorganic & medicinal chemistry, , Aug-15, Volume: 16, Issue:16, 2008
Three dimensional pharmacophore modeling of human CYP17 inhibitors. Potential agents for prostate cancer therapy.Journal of medicinal chemistry, , Jun-05, Volume: 46, Issue:12, 2003
Design, synthesis, and evaluation of (2S,4R)-Ketoconazole sulfonamide analogs as potential treatments for Metabolic Syndrome.Bioorganic & medicinal chemistry letters, , 12-01, Volume: 26, Issue:23, 2016
Discovery and development of Galeterone (TOK-001 or VN/124-1) for the treatment of all stages of prostate cancer.Journal of medicinal chemistry, , Mar-12, Volume: 58, Issue:5, 2015
Discovery of new 7-substituted-4-imidazolylmethyl coumarins and 4'-substituted-2-imidazolyl acetophenones open analogues as potent and selective inhibitors of steroid-11β-hydroxylase.European journal of medicinal chemistry, , Jan-07, Volume: 89, 2015
Heteroatom insertion into 3,4-dihydro-1H-quinolin-2-ones leads to potent and selective inhibitors of human and rat aldosterone synthase.European journal of medicinal chemistry, , Jan-27, Volume: 90, 2015
Design, synthesis, and biological evaluation of imidazolyl derivatives of 4,7-disubstituted coumarins as aromatase inhibitors selective over 17-α-hydroxylase/C17-20 lyase.Journal of medicinal chemistry, , Mar-24, Volume: 54, Issue:6, 2011
Fine-tuning the selectivity of aldosterone synthase inhibitors: structure-activity and structure-selectivity insights from studies of heteroaryl substituted 1,2,5,6-tetrahydropyrrolo[3,2,1-ij]quinolin-4-one derivatives.Journal of medicinal chemistry, , Apr-14, Volume: 54, Issue:7, 2011
N-(Pyridin-3-yl)benzamides as selective inhibitors of human aldosterone synthase (CYP11B2).Bioorganic & medicinal chemistry letters, , Jan-01, Volume: 21, Issue:1, 2011
Replacement of imidazolyl by pyridyl in biphenylmethylenes results in selective CYP17 and dual CYP17/CYP11B1 inhibitors for the treatment of prostate cancer.Journal of medicinal chemistry, , Aug-12, Volume: 53, Issue:15, 2010
Novel highly potent and selective nonsteroidal aromatase inhibitors: synthesis, biological evaluation and structure-activity relationships investigation.Journal of medicinal chemistry, , Jul-22, Volume: 53, Issue:14, 2010
Isopropylidene substitution increases activity and selectivity of biphenylmethylene 4-pyridine type CYP17 inhibitors.Journal of medicinal chemistry, , Jul-08, Volume: 53, Issue:13, 2010
Novel CYP17 inhibitors: synthesis, biological evaluation, structure-activity relationships and modelling of methoxy- and hydroxy-substituted methyleneimidazolyl biphenyls.European journal of medicinal chemistry, , Volume: 44, Issue:7, 2009
Synthesis, biological evaluation and molecular modelling studies of novel ACD- and ABD-ring steroidomimetics as inhibitors of CYP17.Bioorganic & medicinal chemistry letters, , Jan-01, Volume: 18, Issue:1, 2008
Synthesis, biological evaluation, and molecular modeling studies of methylene imidazole substituted biaryls as inhibitors of human 17alpha-hydroxylase-17,20-lyase (CYP17)--part II: Core rigidification and influence of substituents at the methylene bridge.Bioorganic & medicinal chemistry, , Aug-15, Volume: 16, Issue:16, 2008
Synthesis, biological evaluation and molecular modelling studies of methyleneimidazole substituted biaryls as inhibitors of human 17alpha-hydroxylase-17,20-lyase (CYP17). Part I: Heterocyclic modifications of the core structure.Bioorganic & medicinal chemistry, , Feb-15, Volume: 16, Issue:4, 2008
Novel aldosterone synthase inhibitors with extended carbocyclic skeleton by a combined ligand-based and structure-based drug design approach.Journal of medicinal chemistry, , Oct-09, Volume: 51, Issue:19, 2008
Synthesis, biological evaluation, and molecular modeling of abiraterone analogues: novel CYP17 inhibitors for the treatment of prostate cancer.Journal of medicinal chemistry, , Aug-28, Volume: 51, Issue:16, 2008
Overcoming undesirable CYP1A2 inhibition of pyridylnaphthalene-type aldosterone synthase inhibitors: influence of heteroaryl derivatization on potency and selectivity.Journal of medicinal chemistry, , Aug-28, Volume: 51, Issue:16, 2008
In vivo active aldosterone synthase inhibitors with improved selectivity: lead optimization providing a series of pyridine substituted 3,4-dihydro-1H-quinolin-2-one derivatives.Journal of medicinal chemistry, , Dec-25, Volume: 51, Issue:24, 2008
Novel C-17-heteroaryl steroidal CYP17 inhibitors/antiandrogens: synthesis, in vitro biological activity, pharmacokinetics, and antitumor activity in the LAPC4 human prostate cancer xenograft model.Journal of medicinal chemistry, , Apr-21, Volume: 48, Issue:8, 2005
A new class of nonsteroidal aromatase inhibitors: design and synthesis of chromone and xanthone derivatives and inhibition of the P450 enzymes aromatase and 17 alpha-hydroxylase/C17,20-lyase.Journal of medicinal chemistry, , Mar-01, Volume: 44, Issue:5, 2001
Synthesis and evaluation of 17-aliphatic heterocycle-substituted steroidal inhibitors of 17alpha-hydroxylase/C17-20-lyase (P450 17).Journal of medicinal chemistry, , Nov-16, Volume: 43, Issue:23, 2000
Synthesis and evaluation of novel steroidal oxime inhibitors of P450 17 (17 alpha-hydroxylase/C17-20-lyase) and 5 alpha-reductase types 1 and 2.Journal of medicinal chemistry, , Nov-02, Volume: 43, Issue:22, 2000
Novel 17-azolyl steroids, potent inhibitors of human cytochrome 17 alpha-hydroxylase-C17,20-lyase (P450(17) alpha): potential agents for the treatment of prostate cancer.Journal of medicinal chemistry, , Mar-12, Volume: 41, Issue:6, 1998
17-Imidazolyl, pyrazolyl, and isoxazolyl androstene derivatives. Novel steroidal inhibitors of human cytochrome C17,20-lyase (P450(17 alpha).Journal of medicinal chemistry, , Sep-26, Volume: 40, Issue:20, 1997
Synthesis and evaluation of pregnane derivatives as inhibitors of human testicular 17 alpha-hydroxylase/C17,20-lyase.Journal of medicinal chemistry, , Oct-11, Volume: 39, Issue:21, 1996
3- and 4-pyridylalkyl adamantanecarboxylates: inhibitors of human cytochrome P450(17 alpha) (17 alpha-hydroxylase/C17,20-lyase). Potential nonsteroidal agents for the treatment of prostatic cancer.Journal of medicinal chemistry, , Aug-16, Volume: 39, Issue:17, 1996
Novel steroidal inhibitors of human cytochrome P45017 alpha (17 alpha-hydroxylase-C17,20-lyase): potential agents for the treatment of prostatic cancer.Journal of medicinal chemistry, , Jun-23, Volume: 38, Issue:13, 1995
Esters of 3-pyridylacetic acid that combine potent inhibition of 17 alpha-hydroxylase/C17,20-lyase (cytochrome P45017 alpha) with resistance to esterase hydrolysis.Journal of medicinal chemistry, , Oct-13, Volume: 38, Issue:21, 1995
Design, Synthesis, and Biological Evaluation of Androgen Receptor Degrading and Antagonizing Bifunctional Steroidal Analogs for the Treatment of Advanced Prostate Cancer.Journal of medicinal chemistry, , 09-22, Volume: 65, Issue:18, 2022
Structure-Based Design of Inhibitors with Improved Selectivity for Steroidogenic Cytochrome P450 17A1 over Cytochrome P450 21A2.Journal of medicinal chemistry, , 06-14, Volume: 61, Issue:11, 2018
Discovery of novel 1,2,3,4-tetrahydrobenzo[4, 5]thieno[2, 3-c]pyridine derivatives as potent and selective CYP17 inhibitors.European journal of medicinal chemistry, , May-26, Volume: 132, 2017
Identification of Novel Steroidal Androgen Receptor Degrading Agents Inspired by Galeterone 3β-Imidazole Carbamate.ACS medicinal chemistry letters, , Jul-14, Volume: 7, Issue:7, 2016
Discovery and development of Galeterone (TOK-001 or VN/124-1) for the treatment of all stages of prostate cancer.Journal of medicinal chemistry, , Mar-12, Volume: 58, Issue:5, 2015
Modulation of cytochromes P450 with xanthone-based molecules: from aromatase to aldosterone synthase and steroid 11β-hydroxylase inhibition.Journal of medicinal chemistry, , Feb-28, Volume: 56, Issue:4, 2013
Highly potent and selective nonsteroidal dual inhibitors of CYP17/CYP11B2 for the treatment of prostate cancer to reduce risks of cardiovascular diseases.Journal of medicinal chemistry, , Aug-08, Volume: 56, Issue:15, 2013
Novel imidazol-1-ylmethyl substituted 1,2,5,6-tetrahydropyrrolo[3,2,1-ij]quinolin-4-ones as potent and selective CYP11B1 inhibitors for the treatment of Cushing's syndrome.Journal of medicinal chemistry, , Jul-26, Volume: 55, Issue:14, 2012
Replacement of imidazolyl by pyridyl in biphenylmethylenes results in selective CYP17 and dual CYP17/CYP11B1 inhibitors for the treatment of prostate cancer.Journal of medicinal chemistry, , Aug-12, Volume: 53, Issue:15, 2010
Isopropylidene substitution increases activity and selectivity of biphenylmethylene 4-pyridine type CYP17 inhibitors.Journal of medicinal chemistry, , Jul-08, Volume: 53, Issue:13, 2010
Novel CYP17 inhibitors: synthesis, biological evaluation, structure-activity relationships and modelling of methoxy- and hydroxy-substituted methyleneimidazolyl biphenyls.European journal of medicinal chemistry, , Volume: 44, Issue:7, 2009
Synthesis, biological evaluation and molecular modelling studies of novel ACD- and ABD-ring steroidomimetics as inhibitors of CYP17.Bioorganic & medicinal chemistry letters, , Jan-01, Volume: 18, Issue:1, 2008
Synthesis, biological evaluation, and molecular modeling studies of methylene imidazole substituted biaryls as inhibitors of human 17alpha-hydroxylase-17,20-lyase (CYP17)--part II: Core rigidification and influence of substituents at the methylene bridge.Bioorganic & medicinal chemistry, , Aug-15, Volume: 16, Issue:16, 2008
Synthesis, biological evaluation and molecular modelling studies of methyleneimidazole substituted biaryls as inhibitors of human 17alpha-hydroxylase-17,20-lyase (CYP17). Part I: Heterocyclic modifications of the core structure.Bioorganic & medicinal chemistry, , Feb-15, Volume: 16, Issue:4, 2008
Synthesis, biological evaluation, and molecular modeling of abiraterone analogues: novel CYP17 inhibitors for the treatment of prostate cancer.Journal of medicinal chemistry, , Aug-28, Volume: 51, Issue:16, 2008
Novel C-17-heteroaryl steroidal CYP17 inhibitors/antiandrogens: synthesis, in vitro biological activity, pharmacokinetics, and antitumor activity in the LAPC4 human prostate cancer xenograft model.Journal of medicinal chemistry, , Apr-21, Volume: 48, Issue:8, 2005
Three dimensional pharmacophore modeling of human CYP17 inhibitors. Potential agents for prostate cancer therapy.Journal of medicinal chemistry, , Jun-05, Volume: 46, Issue:12, 2003
The 16,17-double bond is needed for irreversible inhibition of human cytochrome p45017alpha by abiraterone (17-(3-pyridyl)androsta-5, 16-dien-3beta-ol) and related steroidal inhibitors.Journal of medicinal chemistry, , Dec-31, Volume: 41, Issue:27, 1998
Novel steroidal inhibitors of human cytochrome P45017 alpha (17 alpha-hydroxylase-C17,20-lyase): potential agents for the treatment of prostatic cancer.Journal of medicinal chemistry, , Jun-23, Volume: 38, Issue:13, 1995
[no title available],
Design and synthesis of functionalized piperazin-1yl-(E)-stilbenes as inhibitors of 17α-hydroxylase-C17,20-lyase (Cyp17).Bioorganic & medicinal chemistry letters, , 07-15, Volume: 28, Issue:13, 2018
Design, synthesis, and evaluation of (2S,4R)-Ketoconazole sulfonamide analogs as potential treatments for Metabolic Syndrome.Bioorganic & medicinal chemistry letters, , 12-01, Volume: 26, Issue:23, 2016
Synthesis, biological evaluation, and molecular modeling of abiraterone analogues: novel CYP17 inhibitors for the treatment of prostate cancer.Journal of medicinal chemistry, , Aug-28, Volume: 51, Issue:16, 2008
Multistep Binding of the Non-Steroidal Inhibitors Orteronel and Seviteronel to Human Cytochrome P450 17A1 and Relevance to Inhibition of Enzyme Activity.Journal of medicinal chemistry, , 06-25, Volume: 63, Issue:12, 2020
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.Bioorganic & medicinal chemistry, , Nov-01, Volume: 19, Issue:21, 2011
[no title available],
Design, Synthesis, and Biological Evaluation of Androgen Receptor Degrading and Antagonizing Bifunctional Steroidal Analogs for the Treatment of Advanced Prostate Cancer.Journal of medicinal chemistry, , 09-22, Volume: 65, Issue:18, 2022
Structure-Based Design of Inhibitors with Improved Selectivity for Steroidogenic Cytochrome P450 17A1 over Cytochrome P450 21A2.Journal of medicinal chemistry, , 06-14, Volume: 61, Issue:11, 2018
Identification of Novel Steroidal Androgen Receptor Degrading Agents Inspired by Galeterone 3β-Imidazole Carbamate.ACS medicinal chemistry letters, , Jul-14, Volume: 7, Issue:7, 2016
Discovery and development of Galeterone (TOK-001 or VN/124-1) for the treatment of all stages of prostate cancer.Journal of medicinal chemistry, , Mar-12, Volume: 58, Issue:5, 2015
Systematic structure modifications of multitarget prostate cancer drug candidate galeterone to produce novel androgen receptor down-regulating agents as an approach to treatment of advanced prostate cancer.Journal of medicinal chemistry, , Jun-27, Volume: 56, Issue:12, 2013
[no title available],
Enables
This protein enables 5 target(s):
| Target | Category | Definition |
|---|
| steroid 17-alpha-monooxygenase activity | molecular function | Catalysis of the reaction: a steroid + AH2 + O2 = a 17a-hydroxysteroid + A + H2O. [EC:1.14.14.19] |
| iron ion binding | molecular function | Binding to an iron (Fe) ion. [GOC:ai] |
| oxygen binding | molecular function | Binding to oxygen (O2). [GOC:jl] |
| heme binding | molecular function | Binding to a heme, a compound composed of iron complexed in a porphyrin (tetrapyrrole) ring. [GOC:ai] |
| 17-alpha-hydroxyprogesterone aldolase activity | molecular function | Catalysis of the reaction: 17alpha-hydroxyprogesterone + O2 + reduced NADPH--hemoprotein reductase = acetate + androst-4-ene-3,17-dione + 2 H+ + H2O + oxidized NADPH--hemoprotein reductase. [MetaCyc:4.1.2.30-RXN, RHEA:14753] |
Located In
This protein is located in 4 target(s):
| Target | Category | Definition |
|---|
| endoplasmic reticulum | cellular component | The irregular network of unit membranes, visible only by electron microscopy, that occurs in the cytoplasm of many eukaryotic cells. The membranes form a complex meshwork of tubular channels, which are often expanded into slitlike cavities called cisternae. The ER takes two forms, rough (or granular), with ribosomes adhering to the outer surface, and smooth (with no ribosomes attached). [ISBN:0198506732] |
| endoplasmic reticulum membrane | cellular component | The lipid bilayer surrounding the endoplasmic reticulum. [GOC:mah] |
| axon | cellular component | The long process of a neuron that conducts nerve impulses, usually away from the cell body to the terminals and varicosities, which are sites of storage and release of neurotransmitter. [GOC:nln, ISBN:0198506732] |
| neuronal cell body | cellular component | The portion of a neuron that includes the nucleus, but excludes cell projections such as axons and dendrites. [GOC:go_curators] |
Involved In
This protein is involved in 7 target(s):
| Target | Category | Definition |
|---|
| steroid biosynthetic process | biological process | The chemical reactions and pathways resulting in the formation of steroids, compounds with a 1,2,cyclopentanoperhydrophenanthrene nucleus; includes de novo formation and steroid interconversion by modification. [GOC:go_curators] |
| androgen biosynthetic process | biological process | The chemical reactions and pathways resulting in the formation of androgens, C19 steroid hormones that can stimulate the development of male sexual characteristics. [ISBN:0198506732] |
| glucocorticoid biosynthetic process | biological process | The chemical reactions and pathways resulting in the formation of glucocorticoids, hormonal C21 corticosteroids synthesized from cholesterol. [ISBN:0198506732] |
| sex differentiation | biological process | The establishment of the sex of an organism by physical differentiation. [GOC:ai] |
| steroid metabolic process | biological process | The chemical reactions and pathways involving steroids, compounds with a 1,2,cyclopentanoperhydrophenanthrene nucleus. [ISBN:0198547684] |
| hormone biosynthetic process | biological process | The chemical reactions and pathways resulting in the formation of any hormone, naturally occurring substances secreted by specialized cells that affects the metabolism or behavior of other cells possessing functional receptors for the hormone. [GOC:jl] |
| progesterone metabolic process | biological process | The chemical reactions and pathways involving progesterone, a steroid hormone produced in the ovary which prepares and maintains the uterus for pregnancy. Also found in plants. [GOC:jl, http://www.cogsci.princeton.edu/] |