DOCSLIB.ORG

Steroids an Overview on 5-Reductase Inhibitors

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Steroids an Overview on 5-Reductase Inhibitors Steroids 75 (2010) 109–153 Contents lists available at ScienceDirect Steroids journal homepage: www.elsevier.com/locate/steroids Review An overview on 5␣-reductase inhibitors Saurabh Aggarwal a, Suresh Thareja a, Abhilasha Verma a, Tilak Raj Bhardwaj a,b, Manoj Kumar a,∗ a University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India b I. S. F College of Pharmacy, Ferozepur Road, Moga, Punjab 142001, India article info abstract Article history: Benign prostatic hyperplasia (BPH) is the noncancerous proliferation of the prostate gland associated Received 13 July 2009 with benign prostatic obstruction and lower urinary tract symptoms (LUTS) such as frequency, hesitancy, Received in revised form 9 October 2009 urgency, etc. Its prevalence increases with age affecting around 70% by the age of 70 years. High activity of Accepted 20 October 2009 5␣-reductase enzyme in humans results in excessive dihydrotestosterone levels in peripheral tissues and Available online 30 October 2009 hence suppression of androgen action by 5␣-reductase inhibitors is a logical treatment for BPH as they inhibit the conversion of testosterone to dihydrotestosterone. Finasteride (13) was the first steroidal 5␣- Keywords: reductase inhibitor approved by U.S. Food and Drug Administration (USFDA). In human it decreases the 5␣-Reductase inhibitors Androgens prostatic DHT level by 70–90% and reduces the prostatic size. Dutasteride (27) another related analogue ␣ Azasteroids has been approved in 2002. Unlike Finasteride, Dutasteride is a competitive inhibitor of both 5 -reductase Testosterone type I and type II isozymes, reduced DHT levels >90% following 1 year of oral administration. A number BPH of classes of non-steroidal inhibitors of 5␣-reductase have also been synthesized generally by removing 5␣-Dihydrotestosterone one or more rings from the azasteroidal structure or by an early non-steroidal lead (ONO-3805) (261). In this review all categories of inhibitors of 5␣-reductase have been covered. © 2009 Elsevier Inc. All rights reserved. Contents 1. Introduction .......................................................................................................................................... 110 2. Enzyme 5␣-reductase ................................................................................................................................ 110 3. Steroidal 5␣-reductase inhibitors ................................................................................................................... 111 4. 2- and 3-Azasteroids ................................................................................................................................. 111 5. 4-Azasteroids......................................................................................................................................... 112 6. 6-Azasteroids......................................................................................................................................... 121 7. 7-Azasteroids......................................................................................................................................... 124 8. 8-Azasteroids......................................................................................................................................... 124 9. 9-Azasteroids......................................................................................................................................... 124 10. 19-Nor-10-azasteroids ............................................................................................................................. 124 11. 11-, 12a-, 13-Azasteroids ........................................................................................................................... 125 12. 15- and 16-Azasteroids ............................................................................................................................. 125 13. 17- and 17a-Aza-D-homosteroids .................................................................................................................. 125 14. Diazasteroids ....................................................................................................................................... 125 15. 11,13,15-Triazasteroids............................................................................................................................. 126 16. B,D-Dihomo-azasteroids............................................................................................................................ 126 17. Des-AB-azasteroids ................................................................................................................................. 126 18. Steroidal 3-carboxylic/phosphonic/phosphinic acids .............................................................................................. 127 19. Diazoketone steroids ............................................................................................................................... 128 20. 4-Substituted steroids .............................................................................................................................. 128 21. Steroidal oximes .................................................................................................................................... 129 22. Steroidal tetrahydrooxazin-2-ones................................................................................................................. 129 ∗ Corresponding author. Tel.: +91 172 2534115; fax: +91 172 2534112. E-mail addresses: [email protected] (S. Aggarwal), manoj [email protected] (M. Kumar). 0039-128X/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.steroids.2009.10.005 110 S. Aggarwal et al. / Steroids 75 (2010) 109–153 23. 16-Substituted steroids ............................................................................................................................. 130 24. 6-Methylene steroidal derivatives ................................................................................................................. 130 25. Seco steroids ........................................................................................................................................ 131 26. Derivatives of natural substrate: pregnane ........................................................................................................ 131 27. Non-steroidal 5␣-reductase inhibitors ............................................................................................................. 135 28. Mimics of 4-azasteroids: benzo[f]quinolinones.................................................................................................... 135 29. Pyridones, quinolinones and piperidines .......................................................................................................... 136 30. Mimics of 6-azasteroids: benzo[c] quinolinones................................................................................................... 139 31. Mimics of 10-azasteroids: benzo[c] quinolizinones ............................................................................................... 139 32. Non-steroidal aryl acids ............................................................................................................................ 141 33. Bisubstrate inhibitors ............................................................................................................................... 146 34. Miscellaneous non-steroidal inhibitors ............................................................................................................ 147 35. Conclusion and future ahead ....................................................................................................................... 149 Acknowledgements .................................................................................................................................. 149 References ........................................................................................................................................... 149 1. Introduction values for relevant compounds have been compared according to the molecular class. The values given are not comparable across Benign prostatic hyperplasia (BPH) is the noncancerous growth the studies and in each comparison a standard taken in the study of the prostate gland resulting due to over-proliferation of the is mentioned. stromal and glandular elements of the prostate [1]. It is caused due to the augmented levels of the androgen dihydrotestosterone 2. Enzyme 5␣-reductase (DHT). In BPH, microscopic foci within specific regions of the prostate grows to form macroscopic nodules which eventually dis- A significant correlation between the androgens and prostate is place the normal prostatic tissue and results into the uretheral well known. Testicular androgens constitute the most important compression. This compression resulting due to increased cell pro- mitogenic factor in vivo for the prostate [11]. Normal circulating liferation and/or impaired apoptosis causes physical enlargement levels of androgens are required for the maintenance of structural of the prostate gland and is referred to as static component. In function, growth and integrity of the prostate tissue. However, addition dynamic component involves sympathetic nerve stim- androgens have no direct effect on prostatic epithelial cells in ulation causing contraction of prostatic and uretheral smooth culture [12].
Load more

Recommended publications
  • Interoperability in Toxicology: Connecting Chemical, Biological, and Complex Disease Data
    INTEROPERABILITY IN TOXICOLOGY: CONNECTING CHEMICAL, BIOLOGICAL, AND COMPLEX DISEASE DATA Sean Mackey Watford A dissertation submitted to the faculty at the University of North Carolina at Chapel Hill in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Gillings School of Global Public Health (Environmental Sciences and Engineering). Chapel Hill 2019 Approved by: Rebecca Fry Matt Martin Avram Gold David Reif Ivan Rusyn © 2019 Sean Mackey Watford ALL RIGHTS RESERVED ii ABSTRACT Sean Mackey Watford: Interoperability in Toxicology: Connecting Chemical, Biological, and Complex Disease Data (Under the direction of Rebecca Fry) The current regulatory framework in toXicology is expanding beyond traditional animal toXicity testing to include new approach methodologies (NAMs) like computational models built using rapidly generated dose-response information like US Environmental Protection Agency’s ToXicity Forecaster (ToXCast) and the interagency collaborative ToX21 initiative. These programs have provided new opportunities for research but also introduced challenges in application of this information to current regulatory needs. One such challenge is linking in vitro chemical bioactivity to adverse outcomes like cancer or other complex diseases. To utilize NAMs in prediction of compleX disease, information from traditional and new sources must be interoperable for easy integration. The work presented here describes the development of a bioinformatic tool, a database of traditional toXicity information with improved interoperability, and efforts to use these new tools together to inform prediction of cancer and complex disease. First, a bioinformatic tool was developed to provide a ranked list of Medical Subject Heading (MeSH) to gene associations based on literature support, enabling connection of compleX diseases to genes potentially involved.
    [Show full text]
  • Diabejesg\Re
    DIABEJESG\RE Book Reviews critique publications related to diabetes of in- Information for Authors terest to professionals. Letters & Comments include opinions on topics published in CONTENT the journal or relating to diabetes in general. Diabetes Care publishes original articles and reviews of human Organization Section includes announcement of meetings, spe- and clinical research intended to increase knowledge, stimulate cial events, and American Diabetes Association business. research, and promote better management of people with dia- betes mellitus. Emphasis is on human studies reporting on the GENERAL GUIDELINES pathophysiology and treatment of diabetes and its complications; genetics; epidemiology; psychosocial adaptation; education; and Diabetes Care publishes only material that has not been printed the development, validation, and application of accepted and new previously or is submitted elsewhere without appropriate anno- therapies. Topics covered are of interest to clinically oriented tation. In submitting an article, the author(s) must state in a cov- physicians, researchers, epidemiologists, psychologists, diabetes ering letter (see below) that no part of the material is under con- educators, and other professionals. sideration for publication elsewhere or has already been published, Diabetes publishes original research about the physiology and including tables, figures, symposia, proceedings, preliminary pathophysiology of diabetes mellitus. Submitted manuscripts can communications, books, and invited articles. Conflicts of interest report any aspect of laboratory, animal, or human research. Em- or support of private interests must be clearly explained. All hu- phasis is on investigative reports focusing on areas such as the man investigation must be conducted according to the principles pathogenesis of diabetes and its complications, normal and path- expressed in the Declaration of Helsinki.
    [Show full text]
  • 1970Qureshiocr.Pdf (10.44Mb)
    STUDY INVOLVING METABOLISM OF 17-KETOSTEROIDS AND 17-HYDROXYCORTICOSTEROIDS OF HEALTHY YOUNG MEN DURING AMBULATION AND RECUMBENCY A DISSERTATION SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY IN NUTRITION IN THE GRADUATE DIVISION OF THE TEXAS WOI\IIAN 'S UNIVERSITY COLLEGE OF HOUSEHOLD ARTS AND SCIENCES BY SANOBER QURESHI I B .Sc. I M.S. DENTON I TEXAS MAY I 1970 ACKNOWLEDGMENTS The author wishes to express her sincere gratitude to those who assisted her with her research problem and with the preparation of this dissertation. To Dr. Pauline Beery Mack, Director of the Texas Woman's University Research Institute, for her invaluable assistance and gui­ dance during the author's entire graduate program, and for help in the preparation of this dissertation; To the National Aeronautics and Space Administration for their support of the research project of which the author's study is a part; To Dr. Elsa A. Dozier for directing the author's s tucly during 1969, and to Dr. Kathryn Montgomery beginning in early 1970, for serving as the immeclia te director of the author while she was working on the completion of the investic;ation and the preparation of this dis- sertation; To Dr. Jessie Bateman, Dean of the College of Household Arts and Sciences, for her assistance in all aspects of the author's graduate program; iii To Dr. Ralph Pyke and Mr. Walter Gilchrist 1 for their ass is­ tance and generous kindness while the author's research program was in progress; To Mr. Eugene Van Hooser 1 for help during various parts of her research program; To Dr.
    [Show full text]
  • The Effects of Exogenous ACTH on 5-3B-Hydroxysteroid Dehydrogenase Activity in the Embryonic Avian Adrenal Gland
    Loyola University Chicago Loyola eCommons Master's Theses Theses and Dissertations 1968 The Effects of Exogenous ACTH on 5-3b-hydroxysteroid Dehydrogenase Activity in the Embryonic Avian Adrenal Gland Grover Charles Ericson Loyola University Chicago Follow this and additional works at: https://ecommons.luc.edu/luc_theses Part of the Medicine and Health Sciences Commons Recommended Citation Ericson, Grover Charles, "The Effects of Exogenous ACTH on 5-3b-hydroxysteroid Dehydrogenase Activity in the Embryonic Avian Adrenal Gland" (1968). Master's Theses. 2264. https://ecommons.luc.edu/luc_theses/2264 This Thesis is brought to you for free and open access by the Theses and Dissertations at Loyola eCommons. It has been accepted for inclusion in Master's Theses by an authorized administrator of Loyola eCommons. For more information, please contact [email protected]. This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License. Copyright © 1968 Grover Charles Ericson THE EFFECTS OF EXOGENOUS ACTH ON d -JB-HYDROXYSTEROID DEHYDROGENASE ACTIVITY IN THE EMBRYONIC AVIAN ADRENAL GLAND by Grover Charles Ericson A The.is Submitted to the Faculty ot the Graduate School of La.vo1. University in Partial Fulfillment ot the Requirements for the Degree ot Master ot Science February 1968 BIOGRAPHY Grover Charles Ericson was born in Oak Park, D.linois, on February 17. 1941. He •• graduated f'rom the Naperville COIIUlIW1ity High School, Naperville. D.l1nois in June, 19.59. He entered North Central College, Naperville. Illinois, in September, 19.59, and was awarded the Bachelor of Arts degree in June, 1964. While attending North Central College.
    [Show full text]
  • A Thesis Entitled "APPLICATIONS of GAS CHROMATOGRAPHY
    A Thesis entitled "APPLICATIONS OF GAS CHROMATOGRAPHY - MASS SPECTROMETRY IN STEROID CHEMISTRY" Submitted in part fulfilment of the requirements for admittance to the degree of Doctor of Philosophy in The University of Glasgow by T.A. Baillie, B.Sc. University of Glasgow 1973. ProQuest Number: 11017930 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a com plete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest ProQuest 11017930 Published by ProQuest LLC(2018). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States C ode Microform Edition © ProQuest LLC. ProQuest LLC. 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106- 1346 ACKNOWLEDGEMENTS I would like to express my sincere thanks to Dr. C.3.W. Brooks for his guidance and encouragement at all times, and to Professors R.A. Raphael, F.R.S., and G.W. Kirby, for the opportunity to carry out this research. Thanks are also due to my many colleagues for useful discussions, and in particular to Dr. B.S. Middleditch who was associated with me in the work described in Section 3 of this thesis. The work was carried out during the tenure of an S.R.C. Research Studentship, which is gratefully acknowledged. Finally, I would like to thank Miss 3.H.
    [Show full text]
  • University Microfilms, Inc., Ann Arbor, Michigan ADRENOCORTICAL STEROID PROFILE IN
    This dissertation has been Mic 61-2820 microfilmed exactly as received BESCH, Paige Keith. ADRENOCORTICAL STEROID PROFILE IN THE HYPERTENSIVE DOG. The Ohio State University, Ph.D., 1961 Chemistry, biological University Microfilms, Inc., Ann Arbor, Michigan ADRENOCORTICAL STEROID PROFILE IN THE HYPERTENSIVE DOG DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of the Ohio State University By Paige Keith Besch, B. S., M. S. The Ohio State University 1961 Approved by Katharine A. Brownell Department of Physiology DEDICATION This work is dedicated to my wife, Dr. Norma F. Besch. After having completed her graduate training, she was once again subjected to almost social isolation by the number of hours I spent away from home. It is with sincerest appreciation for her continual encouragement that I dedi­ cate this to her. ACKNOWLEDGMENTS I wish to acknowledge the assistance and encourage­ ment of my Professor, Doctor Katharine A. Brownell. Equally important to the development of this project are the experience and information obtained through the association with Doctor Frank A. Hartman, who over the years has, along with Doctor Brownell, devoted his life to the development of many of the techniques used in this study. It is also with extreme sincerity that I wish to ac­ knowledge the assistance of Mr. David J. Watson. He has never complained when asked to work long hours at night or weekends. Our association has been a fruitful one. I also wish to acknowledge the encouragement of my former Professor, employer and good friend, Doctor Joseph W.
    [Show full text]
  • The Hormonal Treatment of Sexual Offenders JOHN Mcd
    The Hormonal Treatment of Sexual Offenders JOHN McD. W. BRADFORD, MB The hormonal treatment of sexual offenders is part of a pharmacological approach to the reduction of the sexual drive. Sexual drive reduction can also be brought about by stereotaxic neurosurgery and castration. These other methods of sexual drive reduction are closely related to the phar­ macological approach, and all are dependent on the complex interactions between higher central nervous system functions, located in the cortex and limbic systems, and neuroendocrine mechanisms mediated via the hypothalamic pituitary axis, the gonads, and their various feed-back mechanisms. The higher functions of the central nervous system are chan­ neled through the hypothalamic-pituitary axis where complex neurological correlates of behavior are transformed into neuroendocrine responses. Gonatrophin releasing factor (GRF) is released from the hypothalamus irregularly in bursts. The ante rio-pituitary in response releases luteinizing hormone (LH) and follicular stimulating hormone (FSH), also in episodic bursts of secretion. In the normal male, FSH acts on the germinal epithelium of the seminiferous tubules to produce spermatazoa. LH stimulates the Leydig cells to secrete testosterone that is then released into the serum where it forms approximately 95 percent of the plasma testosterone. The other 5 percent in secreted from the adrenal cortex through d4- androstenedione. J During puberty, both sexes show an increase in the volume of gonado­ trophin secretion, and in the male this is associated with increased testos­ terone secretion during sleep. There is an associated circadian rhythm resulting in sleep related increases in gonadotrophic hormone production. J Testosterone in the male regulates spermatogenesis and is responsible for the development of secondary sex characteristics.
    [Show full text]
  • Characterization of Precursor-Dependent Steroidogenesis in Human Prostate Cancer Models
    cancers Article Characterization of Precursor-Dependent Steroidogenesis in Human Prostate Cancer Models Subrata Deb 1 , Steven Pham 2, Dong-Sheng Ming 2, Mei Yieng Chin 2, Hans Adomat 2, Antonio Hurtado-Coll 2, Martin E. Gleave 2,3 and Emma S. Tomlinson Guns 2,3,* 1 Department of Pharmaceutical Sciences, College of Pharmacy, Larkin University, Miami, FL 33169, USA; [email protected] 2 The Vancouver Prostate Centre at Vancouver General Hospital, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada; [email protected] (S.P.); [email protected] (D.-S.M.); [email protected] (M.Y.C.); [email protected] (H.A.); [email protected] (A.H.-C.); [email protected] (M.E.G.) 3 Department of Urologic Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC V5Z 1M9, Canada * Correspondence: [email protected]; Tel.: +1-604-875-4818 Received: 14 August 2018; Accepted: 17 September 2018; Published: 20 September 2018 Abstract: Castration-resistant prostate tumors acquire the independent capacity to generate androgens by upregulating steroidogenic enzymes or using steroid precursors produced by the adrenal glands for continued growth and sustainability. The formation of steroids was measured by liquid chromatography-mass spectrometry in LNCaP and 22Rv1 prostate cancer cells, and in human prostate tissues, following incubation with steroid precursors (22-OH-cholesterol, pregnenolone, 17-OH-pregnenolone, progesterone, 17-OH-progesterone). Pregnenolone, progesterone, 17-OH-pregnenolone, and 17-OH-progesterone increased C21 steroid (5-pregnan-3,20-dione, 5-pregnan-3,17-diol-20-one, 5-pregnan-3-ol-20-one) formation in the backdoor pathway, and demonstrated a trend of stimulating dihydroepiandrosterone or its precursors in the backdoor pathway in LNCaP and 22Rv1 cells.
    [Show full text]
  • United States Patent Office Patented Oct
    2,721,828 United States Patent Office Patented Oct. 25, 1955 2 tained by subjecting starting steroids to the fermenta 2,721,828 tion process of this invention. For example, androstane 3,11,17-trione (male hormone activity) may be obtained PROCESS FOR PRODUCTION OF by fermentation of allopregnane-3,11,20-trione; etio 17-KETOSTEROOS cholane-3,11,20-trione (general anesthetic activity) from Herbert C. Murray, Hickory Corners, and Darey H. Peter pregnane-3,11,20-trione; 3c- or 3.3-hydroxyeticholane son, Kalamazoo Township, Kalamazoo County, Mich., 17-one (anesthetic activity) from the fermentation of assignors to The Upjohn Company, Kalamazoo, Mich., 3a- or 36-hydroxypregnane-20-one or from pregnane a corporation of Michigan 3,20-dione by the side chain fermentation of this in No Drawing. Application October 1, 1953, 10 vention and subsequent reduction with sodium boro Serial No. 383,701 hydride or lithium aluminum hydride; etiocholane-3,6,17 trione (which may be brominated to 4-bromoetiocholane 20 Claims. (C. 195-51) 3,6,17-trione and dehydrobrominated to give 4-andro stene-3,6,17-trione of estrogenic activity) from preg The present invention relates to a novel process for 5 nane-3,6,20-trione by side chain fermentation; adreno the fermentative degradation of the 17-side chain of sterone from the fermentation of 11-ketoprogesterone, 20-oxygenated steroids, especially 20-ketosteroids to cortisone or cortisone acetate; and other like active 17 yield 17-ketosteroids, especially 17-ketoandrostane and ketosteroids. 17-ketoetiocholane compounds. The starting steroid compounds of the present applica The process of the present invention comprises sub 20 tion are the 20-oxygenated steroids, and preferably the jecting a 20-oxygenated steroid, especially a 20-keto 20-hydroxy steroids and the 20-ketosteroids.
    [Show full text]
  • Effect of Methyl Testosterone on Urinary 17- Ketosteroids of Adrenal Origin
    EFFECT OF METHYL TESTOSTERONE ON URINARY 17- KETOSTEROIDS OF ADRENAL ORIGIN E. C. Reifenstein Jr., … , E. Donaldson, E. Carroll J Clin Invest. 1945;24(4):416-434. https://doi.org/10.1172/JCI101620. Research Article Find the latest version: https://jci.me/101620/pdf EFFECT OF METHYL TESTOSTERONE ON URINARY 17-KETOSTEROIDS OF ADRENAL ORIGIN ", 2'8 BY E. C. REIFENSTEIN, JR., A. P. FORBES, F. ALBRIGHT, E. DONALDSON, AND E. CARROLL (From the Medical Service of the Massachusetts General Hospital and from the Department of Medicine of the Harvard Medical School, Boston) (Received for publication July 15, 1944) Urinary 17-ketosteroids or their precursors are the adrenal cortex. Actually to establish the thought to arise from the adrenal cortices and the point it would be necessary to give methyl testos- testes (1). Testosterone propionate is partially terone to a male patient with Addison's disease. excreted as a 17-ketosteroid (2); on the other This was done (Figures 2 and 3), with suggestive hand, 17-methyl testosterone is not excreted as but not conclusive results. Such an experiment such (3 to. 5). It follows that methyl testos- runs into difficulties because the low initial level terone in contradistinction to testosterone pro- of 17-ketosteroid excretion makes the errors intro- pionate, may be used to study the effect of a tes- duced by chromogens and other technical errors tosterone compound on the endogenous produc- relatively more significant. tion of urinary 17-ketosteroids. The present paper is primarily concerned with the effect of CLINICAL CASES methyl testosterone on the urinary 17-ketosteroids The influence of methyl testosterone on 17-ketosteroid of adrenal origin.
    [Show full text]
  • Substituted Steroids
    Universal Capability of 3-Ketosteroid Δ1- Dehydrogenases to Catalyze Δ1-Dehydrogenation of C17- Substituted Steroids Patrycja Wójcik Jerzy Haber Institute of Catalysis and Surface Chemistry Polish Academy of Sciences: Instytut Katalizy i Fizykochemii Powierzchni im Jerzego Habera Polskiej Akademii Nauk Michał Glanowski Jerzy Haber Institute of Catalysis and Surface Chemistry Polish Academy of Sciences: Instytut Katalizy i Fizykochemii Powierzchni im Jerzego Habera Polskiej Akademii Nauk Agnieszka M. Wojtkiewicz Jerzy Haber Institute of Catalysis and Surface Chemistry Polish Academy of Sciences: Instytut Katalizy i Fizykochemii Powierzchni im Jerzego Habera Polskiej Akademii Nauk Ali Rohman Universitas Airlangga Fakultas Sains dan Teknologi M. Szaleniec ( [email protected] ) Jerzy Haber Institute of Catalysis and Surface Chemistry Polish Academy of Sciences: Instytut Katalizy i Fizykochemii Powierzchni im Jerzego Habera Polskiej Akademii Nauk https://orcid.org/0000-0002- 7650-9263 Research Article Keywords: 3-ketosteroid dehydrogenase, KSTD, cholest-4-en-3-one Δ1-dehydrogenase, 3-ketosteroids, 1,2- dehydrogenation, Δ1-dehydrogenation, cholest-4-en-3-one, diosgenone, cholesterol metabolism Posted Date: March 19th, 2021 DOI: https://doi.org/10.21203/rs.3.rs-317042/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Universal capability of 3-ketosteroid Δ1-dehydrogenases to catalyze Δ1-dehydrogenation of C17- substituted steroids Patrycja Wójcik1, Michał Glanowski1,
    [Show full text]
  • Ames II™ Mutagenicity Assay
    Testing of estrogenic and androgenic reference compounds using 2 versions of the yeast-based YES and YAS assay Markus Kamber Xenometrix AG, Gewerbestr. 25, CH - 4123 Allschwil, Switzerland Abstract: Results: The performance of 2 commercially available kits for the detection of estrogenic and androgenic compounds was evaluated. The kits (“XenoScreen” and “XenoScreen XL”, Xenometrix AG, Proficiency Chemicals: Estrogen Agonists and Antagonists Switzerland) are based on yeast cells transfected with the human estrogen and androgen receptors, respectively (YES and YAS, Routledge and Sumpter, 1996). The tests are performed in microtiter Expected Highest tested XenoScreen XenoScreen XenoScreen XL XenoScreen XL 1) -1 -1 -1 -1 -1 plates and are able to detect both activating (agonist) and inhibiting (antagonist) activities. Hormonal Name CAS # Class response conc. (M ) EC50 (M ) EC10 (M ) EC50 (M ) EC10 (M ) Remarks activities of test substances are detected using a lacZ reporter gene construct (β-galactosidase) and the highly sensitive substrate CPRG leading to a color change in the medium from yellow to purple. Agonists The XenoScreen kit is based on the original protocol and uses an incubation time of 48 hrs, whereas Steroid 17β-Estradiol 50-28-2 positive 1.0 x 10-8 1.4 x 10-10 4.9 x 10-11 5.0 x 10-11 1.4 x 10-11 the XenoScreen XL kit is based on a modified 18-hr exposure protocol using the enzyme lyticase to Cyclic Hydrocarbon facilitate the release of the β-galactosidase from the yeast cells. Diethylstilbestrol 56-53-1 positive 2.5 x 10-8
    [Show full text]