{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T14:23:24Z","timestamp":1774880604346,"version":"3.50.1"},"reference-count":29,"publisher":"Institute of Biochemistry","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BIOMED KHIM"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:p>Interactions of cytochrome P450 2C9 (CYP2C9) were studied with the antitumor drug abiraterone and  its pharmacologically active metabolite D4A, promising as an agent for prostate cancer treatment. It was shown  by absorption spectroscopy, that both investigated compounds induced spectral changes of CYP2C9, indicating  interactions of the pyridine nitrogen atom with the heme iron ion of the active site of the enzyme, but interactions  of the ligands with the enzyme could be mediated by a water molecule bound to the heme iron ion. Based on the spectral  changes, the values of dissociation constants (KS) for complexes of abiraterone and D4A with CYP2C9 were calculated  as 1.73\u00b10.14 \u03bcM and 3.95\u00b10.16 \u03bcM. Both compounds inhibited O-demethylase activity of CYP2C9 towards  its substrate. At 100 \u03bcM concentration of naproxen the concentrations of abiraterone, D4A and sulfaphenazole  inhibiting CYP2C9 activity by 50% (IC50) were determined as 13.9 \u03bcM, 40 \u03bcM and 41 \u03bcM, respectively.  The obtained results can be used for prognosis of drug-drug interactions at CYP2C9 level during administration  of abiraterone or D4A as an antitumor agent for prostate cancer treatment in complex pharmacotherapy.<\/jats:p>","DOI":"10.18097\/pbmc20226803201","type":"journal-article","created":{"date-parts":[[2022,6,19]],"date-time":"2022-06-19T08:02:39Z","timestamp":1655625759000},"page":"201-211","source":"Crossref","is-referenced-by-count":3,"title":["The interactions of abiraterone and its pharmacologically active metabolite D4A with cytochrome P450 2C9 (CYP2C9)"],"prefix":"10.18097","volume":"68","author":[{"given":"R.A.","family":"Masamrekh","sequence":"first","affiliation":[{"name":"Institute of Biomedical Chemistry, Moscow, Russia; Pirogov Russian National Research Medical University, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.V.","family":"Kuzikov","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Chemistry, Moscow, Russia; Pirogov Russian National Research Medical University, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.A.","family":"Filippova","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Chemistry, Moscow, Russia; Pirogov Russian National Research Medical University, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.A.","family":"Sherbakov","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Chemistry, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.V.","family":"Veselovsky","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Chemistry, Moscow, Russia; Pirogov Russian National Research Medical University, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V.V.","family":"Shumyantseva","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Chemistry, Moscow, Russia; Pirogov Russian National Research Medical University, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"7443","published-online":{"date-parts":[[2022]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Li Z., Bishop A.C., Alyamani M., Garcia J.A., Dreicer R., Bunch D., Liu J., Upadhyay S.K., Auchus R.J., Sharifi N. (2015) Conversion of abiraterone to D4A drives anti-tumour activity in prostate cancer. Nature, 523, 347-351.","DOI":"10.1038\/nature14406"},{"key":"ref2","doi-asserted-by":"publisher","unstructured":"Yoshimoto F.K., Auchus R.J. (2015) The diverse chemistry of cytochrome P450 17A1 (P450c17, CYP17A1). J. Steroid Biochem. Mol. Biol., 151, 52-65.","DOI":"10.1016\/j.jsbmb.2014.11.026"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"Attard G., Reid A.H., Auchus R.J., Hughes B.A., Cassidy A.M., Thompson E., Oommen N.B., Folkerd E., Dowsett M., Arlt W., de Bono J.S. (2012) Clinical and biochemical consequences of CYP17A1 inhibition with abiraterone given with and without exogenous glucocorticoids in castrate men with advanced prostate cancer. J. Clin. Endocrinol. Metab., 97(2), 507-516.","DOI":"10.1210\/jc.2011-2189"},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"Li Z., Alyamani M., Li J., Rogacki K., Abazeed M., Upadhyay S.K., Balk S.P., Taplin M.E., Auchus R.J., Sharifi N. (2016) Redirecting abiraterone metabolism to finetune prostate cancer anti-androgen therapy. Nature, 533(7604), 547-551.","DOI":"10.1038\/nature17954"},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"Salvador J.A., Pinto R.M., Silvestre S.M. (2013) Steroidal 5\u03b1-reductase and 17\u03b1hydroxylase\/17,20-lyase (CYP17) inhibitors useful in the treatment of prostatic diseases. J. Steroid Biochem. Mol Biol., 137, 199-222.","DOI":"10.1016\/j.jsbmb.2013.04.006"},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"Bonnet C., Boudou-Rouquette P., Azoulay-Rutman E., Huillard O., Golmard J.-L., Carton E., No\u00e9 G., Vidal M., Orvoen G., Wakilian A.C., Villeminey C., Blanchet B., Alexandre J., Goldwasser F., Thomas-Schoemann A. (2017) Potential drug-drug interactions with abiraterone in metastatic castration-resistant prostate cancer patients: A prevalence study in France. Cancer Chemother. Pharmacol., 79, 1051-1055.","DOI":"10.1007\/s00280-017-3291-z"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"del Re M., Fogli S., Derosa L., Massari F., de Souza P., Crucitta S., Bracarda S., Santini D., Danesi R. (2017) The role of drug-drug interactions in prostate cancer treatment: Focus on abiraterone acetate\/prednisone and enzalutamide. Cancer Treat. Rev., 55, 71-82.","DOI":"10.1016\/j.ctrv.2017.03.001"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"Masamrekh R.A., Kuzikov A.V., Haurychenka Y.I., Shcherbakov K.A., Veselovsky A.V., Filimonov D.A., Dmitriev A.V., Zavialova M.G., Gilep A.A., Shkel T.V., Strushkevich N.V., Usanov S.A., Archakov A.I., Shumyantseva V.V. (2020) In vitro interactions of abiraterone, erythromycin, and CYP3A4: implications for drug-drug interactions. Fundam. Clin. Pharmacol., 34(1), 120-130.","DOI":"10.1111\/fcp.12497"},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"Friedlander T.W., Ryan C.J. (2010) Adrenal androgen synthesis inhibitor therapies in castration-resistant prostate cancer. In: Drug Management of Prostate Cancer (Figg W., Chau C., Small E., eds.), Springer, New York, NY, pp. 91-100.","DOI":"10.1007\/978-1-60327-829-4_8"},{"key":"ref10","doi-asserted-by":"publisher","unstructured":"Malikova J., Brixius-Anderko S., Udhane S.S., Parween S., Dick B., Bernhardt R., Pandey A.V. (2017) CYP17A1 inhibitor abiraterone, an anti-prostate cancer drug, also inhibits the 21-hydroxylase activity of CYP21A2. J. Steroid Biochem. Mol. Biol., 174, 192-200.","DOI":"10.1016\/j.jsbmb.2017.09.007"},{"key":"ref11","doi-asserted-by":"publisher","unstructured":"Masamrekh R., Filippova T., Haurychenka Y., Shcherbakov K., Veselovsky A., Strushkevich N., Shkel T., Gilep A., Usanov S., Shumyantseva V., Kuzikov A. (2020) Estimation of the inhibiting impact of abiraterone D4A metabolite on human steroid 21-monooxygenase (CYP21A2). Steroids, 154, 108528.","DOI":"10.1016\/j.steroids.2019.108528"},{"key":"ref12","doi-asserted-by":"publisher","unstructured":"Garrido M., Peng H.M., Yoshimoto F.K., Upadhyay S.K., Bratoeff E., Auchus R.J. (2014) A-ring modified steroidal azoles retaining similar potent and slowly reversible CYP17A1 inhibition as abiraterone. J. Steroid Biochem. Mol. Biol., 143, 1-10.","DOI":"10.1016\/j.jsbmb.2014.01.013"},{"key":"ref13","doi-asserted-by":"publisher","unstructured":"Masamrekh R.A., Filippova T.A., Haurychenka Y.I., Sherbakov K.A., Veselovsky A.V., Shumyantseva V.V., Kuzikov A.V. (2020) The interactions of a number of steroid-metabolizing cytochromes P450 with abiraterone D4A metabolite: spectral analysis and molecular docking. Steroids, 162, 108693.","DOI":"10.1016\/j.steroids.2020.108693"},{"key":"ref14","doi-asserted-by":"publisher","unstructured":"Louet M., Labb\u00e9 C.M., Fagnen C., Aono C.M., Homem-de-Mello P., Villoutreix B.O., Miteva M.A. (2018) Insights into molecular mechanisms of drug metabolism dysfunction of human CYP2C9*30. PLoS One, 13(5), e0197249.","DOI":"10.1371\/journal.pone.0197249"},{"key":"ref15","doi-asserted-by":"publisher","unstructured":"Daly A.K., Rettie A.E., Fowler D.M., Miners J.O. (2017) Pharmacogenomics of CYP2C9: functional and clinical considerations. J. Pers. Med., 8(1), 1.","DOI":"10.3390\/jpm8010001"},{"key":"ref16","doi-asserted-by":"publisher","unstructured":"Hoy S.M. (2013) Abiraterone acetate: A review of its use in patients with metastatic castration-resistant prostate cancer. Drugs, 73(18), 2077-2091.","DOI":"10.1007\/s40265-013-0150-z"},{"key":"ref17","doi-asserted-by":"publisher","unstructured":"Haidukevich I.V., Sushko T.A., Tumilovich A.M., Grabovec I.P., Usanov S.A., Gilep A.A. (2018) Different inhibitory effects of azole-containing drugs and pesticides on CYP2C9 polymorphic forms: An in vitro study. Toxicol. In Vitro, 50, 249-256.","DOI":"10.1016\/j.tiv.2018.04.002"},{"key":"ref18","doi-asserted-by":"publisher","unstructured":"Omura T., Sato R. (1964) The carbon monoxide-binding pigment of liver microsomes. Ii. Solubilization, purification, and properties. J. Biol. Chem., 239, 2379-2385.","DOI":"10.1016\/S0021-9258(20)82245-5"},{"key":"ref19","doi-asserted-by":"publisher","unstructured":"Swain N.A., Batchelor D., Beaudoin S., Bechle B.M., Bradley P.A., Brown A.D., Brown B., Butcher K.J., Butt R.P., Chapman M.L., Denton S., Ellis D., Galan S.R.G., Gaulier S.M., Greener B.S., de Groot M.J., Glossop M.S., Gurrell I.K., Hannam J., Johnson M.S., Lin Z., Markworth C.J., Marron B.E., Millan D.S., Nakagawa S., Pike A., Printzenhoff D., Rawson D.J., Ransley S.J., Reister S.M., Sasaki K., Storer R.I., Stupple P.A., West C.W. (2017) Discovery of clinical candidate 4-[2-(5-Amino-1H-pyrazol- 4-yl)-4-chlorophenoxy]-5-chloro-2-fluoro-N-1,3-thiazol-4- ylbenzenesulfonamide (PF-05089771): Design and optimization of diaryl ether aryl sulfonamides as selective inhibitors of NaV1.7. J. Med. Chem., 60(16), 7029-7042.","DOI":"10.1021\/acs.jmedchem.7b00598"},{"key":"ref20","doi-asserted-by":"publisher","unstructured":"Trott O., Olson A.J. (2010) AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem., 31(2), 455-461.","DOI":"10.1002\/jcc.21334"},{"key":"ref21","doi-asserted-by":"publisher","unstructured":"Adasme M.F., Linnemann K.L., Bolz S.N., Kaiser F., Salentin S., Haupt V.J., Schroeder M. (2021) PLIP 2021: Expanding the scope of the protein-ligand interaction profiler to DNA and RNA. Nucleic Acids Res., 49(W1), W530-W534.","DOI":"10.1093\/nar\/gkab294"},{"key":"ref22","doi-asserted-by":"publisher","unstructured":"Kuzikov A.V., Filippova T.A., Masamrekh R.A., Shumyantseva V.V. (2022) Electrochemical determination of (S)-7-hydroxywarfarin for analysis of CYP2C9 catalytic activity. J. Electroanalytical Chemistry, 904, 115937.","DOI":"10.1016\/j.jelechem.2021.115937"},{"key":"ref23","doi-asserted-by":"publisher","unstructured":"Shumyantseva V.V., Bulko T.V., Koroleva P.I., Shikh E.V., Makhova A.A., Kisel M.S., Haidukevich I.V., Gilep A.A. (2022) Human cytochrome P450 2C9 and its polymorphic modifications: Electroanalysis, catalytic properties, and approaches to the regulation of enzymatic activity. Processes, 10(2), 383.","DOI":"10.3390\/pr10020383"},{"key":"ref24","doi-asserted-by":"publisher","unstructured":"Nash T. (1953) The colorimetric estimation of formaldehyde by means of the Hantzsch reaction. Biochem. J., 55(3), 416-421.","DOI":"10.1042\/bj0550416"},{"key":"ref25","doi-asserted-by":"publisher","unstructured":"Luthra A., Denisov I.G., Sligar S.G. (2011) Spectroscopic features of cytochrome P450 reaction intermediates. Arch. Biochem. Biophys., 507(1), 26-35.","DOI":"10.1016\/j.abb.2010.12.008"},{"key":"ref26","doi-asserted-by":"publisher","unstructured":"Denisov I.G., Frank D.J., Sligar S.G. (2009) Cooperative properties of cytochromes P450. Pharmacol. Ther., 124(2), 151-167.","DOI":"10.1016\/j.pharmthera.2009.05.011"},{"key":"ref27","unstructured":"Bourri\u00e9 M., Meunier V., Berger Y., Fabre G. (1996) Cytochrome P450 isoform inhibitors as a tool for the investigation of metabolic reactions catalyzed by human liver microsomes. J. Pharmacol. Exp. Ther., 277(1), 321-332."},{"key":"ref28","doi-asserted-by":"publisher","unstructured":"Miners J.O., Coulter S., Tukey R.H., Veronese M.E., Birkett D.J. (1996) Cytochromes P450, 1A2, and 2C9 are responsible for the human hepatic O-demethylation of R- and S-naproxen. Biochem. Pharmacol., 51(8), 1003-1008.","DOI":"10.1016\/0006-2952(96)85085-4"},{"key":"ref29","doi-asserted-by":"publisher","unstructured":"van Booven D., Marsh S., McLeod H., Carrillo M.W., Sangkuhl K., Klein T.E., Altman R.B. (2010) Cytochrome P450 2C9-CYP2C9. Pharmacogenet. 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