YM116, 2-(1<I>H</I>-Imidazol-4-ylmethyl)-9<I>H</I>-carbazole, Decreases Adrenal Androgen Synthesis by Inhibiting C17-20 Lyase Activity in NCI-H295 Human Adrenocortical Carcinoma Cells
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- Ideyama Yukitaka
- Metabolic Diseases Research, Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.
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- Kudoh Masafumi
- Metabolic Diseases Research, Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.
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- Tanimoto Kyoko
- Metabolic Diseases Research, Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.
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- Susaki Yoko
- Metabolic Diseases Research, Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.
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- Nanya Taiki
- Metabolic Diseases Research, Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.
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- Nakahara Takahito
- Metabolic Diseases Research, Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.
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- Ishikawa Hiroko
- Metabolic Diseases Research, Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.
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- Fujikura Takashi
- Metabolic Diseases Research, Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.
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- Akaza Hideyuki
- Department of Urology, Institute of Clinical Medicine, University of Tsukuba
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- Shikama Hisataka
- Metabolic Diseases Research, Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.
Bibliographic Information
- Other Title
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- YM116,2/(1H/Imidazol/4/ylmethyl)/9H/carbazole,Decreases Adrenal Androgen Synthesis by Inhibiting C17-20 Lyase Activity in NCI-H295 Human Adrenocortical Carcinoma Cells
- YM116, 2-(1H-Imidazol-4-ylmethyl)-9H-carbazole, Decreases Adrenal Androgen Synthesis by Inhibiting Cl7-20 Lyase Activity in NCI-H295 Human Adrenocortical Carcinoma Cells
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Description
The concentrations of androstenedione and dehydroepiandrosterone, products of C17-20 lyase, in the medium after a 6-hr incubation of NCI-H295 cells were decreased by YM116 (2-(1H-imidazol4-ylmethyl)-9H-carbazole) (IC50: 3.6 and 2.1 nM) and ketoconazole (IC50: 54.9 and 54.2 nM). 17αHydroxyprogesterone, a product of 17α-hydroxylase, was increased by YM116 (1 - 30 nM) and by ketoconazole (10 - 300 nM) and then was decreased at higher concentrations of both agents (IC50: 180 nM for YM116, 906 nM for ketoconazole), indicating that YM116 and ketoconazole were 50- and 16.5-fold more specific inhibitors of C17-20 lyase, respectively, than 17α-hydroxylase. Compatible with these findings, progesterone, a substrate of 17α-hydroxylase, was increased by these agents. Cortisol production was inhibited by YM116 and ketoconazole (IC50: 50.4 and 80.9 nM, respectively). YM116 was a 14-fold more potent inhibitor of androstenedione production than cortisol production, whereas ketoconazole was a nonselective inhibitor of the production of both steroids. YM116 and ketoconazole inhibited the C17-20 lyase activity in human testicular microsomes (IC50: 4.2 and 17 nM, respectively). These results demonstrate that YM116 reduces the synthesis of adrenal androgens by preferentially inhibiting C17-20 lyase activity.
Journal
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- The Japanese Journal of Pharmacology
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The Japanese Journal of Pharmacology 79 (2), 213-220, 1999
The Japanese Pharmacological Society
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Details 詳細情報について
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- CRID
- 1390282679261321472
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- NII Article ID
- 10008682403
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- NII Book ID
- AA00691188
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- COI
- 1:CAS:528:DyaK1MXhsFyktrg%3D
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- ISSN
- 13473506
- 00215198
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- NDL BIB ID
- 4663544
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- PubMed
- 10202857
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- Web Site
- http://id.ndl.go.jp/bib/4663544
- https://ndlsearch.ndl.go.jp/books/R000000004-I4663544
- https://api.elsevier.com/content/article/PII:S0021519819309722?httpAccept=text/xml
- https://api.elsevier.com/content/article/PII:S0021519819309722?httpAccept=text/plain
- https://www.jstage.jst.go.jp/article/jjp/79/2/79_2_213/_pdf
- https://search.jamas.or.jp/link/ui/1999177082
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed