Predominant contributions of carboxylesterase 1 and 2 in hydrolysis of anordrin in humans

Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Jinfang JiangDafang Zhong

Abstract

1. Anordrin (2α, 17α-diethynyl-A-nor-5α-androstane-2β, 17β-diol diproprionate) is post-coital contraceptive drug that is on the market in China for more than 30 years. This study aims to elucidate enzymes involved in anordrin hydrolysis, and to evaluate the significant role of carboxylesterases in anordrin hydrolysis in humans. 2. Human liver and intestinal microsomes, recombinant human carboxylesterase were selected as enzyme sources. In human liver microsomes, intrinsic clearance was 684 ± 83 μL/min/mg protein, which was considerably higher than the value of intestine microsomes (94.6 ± 13.3 μL/min/mg protein). Carboxylesterase (CES) 1 has more contribution than CES2 in human liver. 3. Inhibition studies were performed using representative esterase inhibitors to confirm esterase isoforms involved in anordrin hydrolysis. Simvastatin strongly inhibited hydrolytic process of anordrin in liver and intestine microsomes, with IC50 values of 10.9 ± 0.1 and 6.94 ± 0.03 μM, respectively. 4. The present study investigated for the first time hydrolytic enzyme phenotypes of anordrin. Anordrin is predominantly catalyzed by CES1 and CES2 to generate the main active metabolite, anordiol. Moreover, anordrin and its metabolite anordiol can be...Continue Reading

References

Apr 6, 2006·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Masaru HiranoYuichi Sugiyama
Jul 22, 2006·Drug Metabolism and Pharmacokinetics·Teruko Imai
Apr 3, 2008·Journal of Pharmaceutical Sciences·Shiori TakahashiTsuyoshi Yokoi
Apr 3, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Akinobu WatanabeTsuyoshi Yokoi
Jun 15, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Akinobu WatanabeTsuyoshi Yokoi
Oct 12, 2010·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Roger S HolmesLois J Maltais
Apr 17, 2012·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Yuichiro SatoTakashi Usui
Apr 25, 2012·Archives of Biochemistry and Biophysics·Matthew K RossShuqi Xie
Jul 21, 2012·Drug Metabolism and Pharmacokinetics·Tatsuki Fukami, Tsuyoshi Yokoi
Aug 1, 2012·European Journal of Clinical Pharmacology·Hao-Jie Zhu, John S Markowitz
Oct 29, 2013·Cancer Chemotherapy and Pharmacology·Tamer A AhmedMarkos Leggas
Apr 23, 2014·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Mai ShimizuTsuyoshi Yokoi
Mar 10, 2015·Biological & Pharmaceutical Bulletin·Xinwen WangJohn Seth Markowitz
Jul 15, 2015·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Tatsuki FukamiMiki Nakajima

❮ Previous
Next ❯

Citations

Nov 30, 2018·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Qiang FuXibo Zhang
Jun 27, 2021·Chemico-biological Interactions·Yun-Qing SongGuang-Bo Ge

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Takaya KurokawaMiki Nakajima
Drug Metabolism and Disposition : the Biological Fate of Chemicals
Shiori TakahashiTsuyoshi Yokoi
Drug Metabolism and Disposition : the Biological Fate of Chemicals
Mai ShimizuTsuyoshi Yokoi
© 2022 Meta ULC. All rights reserved