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Victoria V Shumyantseva - One of the best experts on this subject based on the ideXlab platform.
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interactions of galeterone and its 3 keto δ4 metabolite d4g with one of the key enzymes of corticoSteroid biosynthesis Steroid 21 Monooxygenase cyp21a2
Fundamental & Clinical Pharmacology, 2020Co-Authors: Rami A Masamrekh, Tatiana A Filippova, A V Veselovsky, Victoria V Shumyantseva, Kirill A Sherbakov, A V KuzikovAbstract:We have investigated interactions of galeterone and its pharmacologically active metabolite - 3-keto-Δ4-galeterone (D4G) - with one of the key enzymes of corticoSteroid biosynthesis - Steroid 21-Monooxygenase (CYP21A2). It was shown by absorption spectroscopy that both compounds induce type I spectral changes of CYP21A2. Spectral dissociation constants (KS ) of complexes of CYP21A2 with galeterone or D4G were calculated as 3.1 ± 0.7 μm and 4.6 ± 0.4 μm, respectively. It was predicted by molecular docking that both ligands similarly bind to the active site of CYP21A2. We have revealed using reconstituted Monooxygenase system that galeterone is a competitive inhibitor of CYP21A2 with the inhibition constant (Ki ) value of 12 ± 3 μm, while D4G at the concentrations of 10 and 25 μm does not inhibit the enzyme. Summarizing, based on the in vitro analyses we detected inhibition of CYP21A2 by galeterone and lack of the influence of D4G on this enzyme.
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estimation of the inhibiting impact of abiraterone d4a metabolite on human Steroid 21 Monooxygenase cyp21a2
Steroids, 2020Co-Authors: Rami A Masamrekh, Tatiana A Filippova, Yaraslau I Haurychenka, Kirill Shcherbakov, A V Veselovsky, N V Strushkevich, T V Shkel, Andrei A Gilep, S A Usanov, Victoria V ShumyantsevaAbstract:Abstract Abiraterone D4A metabolite, the product of 3β-hydroxySteroid dehydrogenase activity toward abiraterone, may serve as a potential antitumor agent for the treatment of prostate cancer. The main adverse effect of abiraterone is the disruption of corticoSteroid biosynthesis, and the more pharmacologically active abiraterone D4A metabolite may have the same issues. We therefore estimated the inhibiting impact of the abiraterone D4A metabolite on one of the key corticoSteroidogenic enzymes – human Steroid 21-Monooxygenase (CYP21A2). Molecular docking of D4A into the active site of CYP21A2 has been predicted to be similar to abiraterone binding with the enzyme. Abiraterone D4A metabolite, similar to abiraterone, induces type II spectral changes of CYP21A2. The spectral dissociation constant for the abiraterone D4A metabolite-CYP21A2 complex was calculated as 3.4 ± 0.5 μM. Abiraterone D4A metabolite demonstrates competitive/mixed type CYP21A2 inhibition with an inhibitory constant of 1.8 ± 0.8 μM, as obtained by Dixon plot. These results make it possible to predict the adverse effects of the new perspective candidate compound for antitumor therapy.
Rami A Masamrekh - One of the best experts on this subject based on the ideXlab platform.
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interactions of galeterone and its 3 keto δ4 metabolite d4g with one of the key enzymes of corticoSteroid biosynthesis Steroid 21 Monooxygenase cyp21a2
Fundamental & Clinical Pharmacology, 2020Co-Authors: Rami A Masamrekh, Tatiana A Filippova, A V Veselovsky, Victoria V Shumyantseva, Kirill A Sherbakov, A V KuzikovAbstract:We have investigated interactions of galeterone and its pharmacologically active metabolite - 3-keto-Δ4-galeterone (D4G) - with one of the key enzymes of corticoSteroid biosynthesis - Steroid 21-Monooxygenase (CYP21A2). It was shown by absorption spectroscopy that both compounds induce type I spectral changes of CYP21A2. Spectral dissociation constants (KS ) of complexes of CYP21A2 with galeterone or D4G were calculated as 3.1 ± 0.7 μm and 4.6 ± 0.4 μm, respectively. It was predicted by molecular docking that both ligands similarly bind to the active site of CYP21A2. We have revealed using reconstituted Monooxygenase system that galeterone is a competitive inhibitor of CYP21A2 with the inhibition constant (Ki ) value of 12 ± 3 μm, while D4G at the concentrations of 10 and 25 μm does not inhibit the enzyme. Summarizing, based on the in vitro analyses we detected inhibition of CYP21A2 by galeterone and lack of the influence of D4G on this enzyme.
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estimation of the inhibiting impact of abiraterone d4a metabolite on human Steroid 21 Monooxygenase cyp21a2
Steroids, 2020Co-Authors: Rami A Masamrekh, Tatiana A Filippova, Yaraslau I Haurychenka, Kirill Shcherbakov, A V Veselovsky, N V Strushkevich, T V Shkel, Andrei A Gilep, S A Usanov, Victoria V ShumyantsevaAbstract:Abstract Abiraterone D4A metabolite, the product of 3β-hydroxySteroid dehydrogenase activity toward abiraterone, may serve as a potential antitumor agent for the treatment of prostate cancer. The main adverse effect of abiraterone is the disruption of corticoSteroid biosynthesis, and the more pharmacologically active abiraterone D4A metabolite may have the same issues. We therefore estimated the inhibiting impact of the abiraterone D4A metabolite on one of the key corticoSteroidogenic enzymes – human Steroid 21-Monooxygenase (CYP21A2). Molecular docking of D4A into the active site of CYP21A2 has been predicted to be similar to abiraterone binding with the enzyme. Abiraterone D4A metabolite, similar to abiraterone, induces type II spectral changes of CYP21A2. The spectral dissociation constant for the abiraterone D4A metabolite-CYP21A2 complex was calculated as 3.4 ± 0.5 μM. Abiraterone D4A metabolite demonstrates competitive/mixed type CYP21A2 inhibition with an inhibitory constant of 1.8 ± 0.8 μM, as obtained by Dixon plot. These results make it possible to predict the adverse effects of the new perspective candidate compound for antitumor therapy.
A V Veselovsky - One of the best experts on this subject based on the ideXlab platform.
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interactions of galeterone and its 3 keto δ4 metabolite d4g with one of the key enzymes of corticoSteroid biosynthesis Steroid 21 Monooxygenase cyp21a2
Fundamental & Clinical Pharmacology, 2020Co-Authors: Rami A Masamrekh, Tatiana A Filippova, A V Veselovsky, Victoria V Shumyantseva, Kirill A Sherbakov, A V KuzikovAbstract:We have investigated interactions of galeterone and its pharmacologically active metabolite - 3-keto-Δ4-galeterone (D4G) - with one of the key enzymes of corticoSteroid biosynthesis - Steroid 21-Monooxygenase (CYP21A2). It was shown by absorption spectroscopy that both compounds induce type I spectral changes of CYP21A2. Spectral dissociation constants (KS ) of complexes of CYP21A2 with galeterone or D4G were calculated as 3.1 ± 0.7 μm and 4.6 ± 0.4 μm, respectively. It was predicted by molecular docking that both ligands similarly bind to the active site of CYP21A2. We have revealed using reconstituted Monooxygenase system that galeterone is a competitive inhibitor of CYP21A2 with the inhibition constant (Ki ) value of 12 ± 3 μm, while D4G at the concentrations of 10 and 25 μm does not inhibit the enzyme. Summarizing, based on the in vitro analyses we detected inhibition of CYP21A2 by galeterone and lack of the influence of D4G on this enzyme.
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estimation of the inhibiting impact of abiraterone d4a metabolite on human Steroid 21 Monooxygenase cyp21a2
Steroids, 2020Co-Authors: Rami A Masamrekh, Tatiana A Filippova, Yaraslau I Haurychenka, Kirill Shcherbakov, A V Veselovsky, N V Strushkevich, T V Shkel, Andrei A Gilep, S A Usanov, Victoria V ShumyantsevaAbstract:Abstract Abiraterone D4A metabolite, the product of 3β-hydroxySteroid dehydrogenase activity toward abiraterone, may serve as a potential antitumor agent for the treatment of prostate cancer. The main adverse effect of abiraterone is the disruption of corticoSteroid biosynthesis, and the more pharmacologically active abiraterone D4A metabolite may have the same issues. We therefore estimated the inhibiting impact of the abiraterone D4A metabolite on one of the key corticoSteroidogenic enzymes – human Steroid 21-Monooxygenase (CYP21A2). Molecular docking of D4A into the active site of CYP21A2 has been predicted to be similar to abiraterone binding with the enzyme. Abiraterone D4A metabolite, similar to abiraterone, induces type II spectral changes of CYP21A2. The spectral dissociation constant for the abiraterone D4A metabolite-CYP21A2 complex was calculated as 3.4 ± 0.5 μM. Abiraterone D4A metabolite demonstrates competitive/mixed type CYP21A2 inhibition with an inhibitory constant of 1.8 ± 0.8 μM, as obtained by Dixon plot. These results make it possible to predict the adverse effects of the new perspective candidate compound for antitumor therapy.
Tatiana A Filippova - One of the best experts on this subject based on the ideXlab platform.
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interactions of galeterone and its 3 keto δ4 metabolite d4g with one of the key enzymes of corticoSteroid biosynthesis Steroid 21 Monooxygenase cyp21a2
Fundamental & Clinical Pharmacology, 2020Co-Authors: Rami A Masamrekh, Tatiana A Filippova, A V Veselovsky, Victoria V Shumyantseva, Kirill A Sherbakov, A V KuzikovAbstract:We have investigated interactions of galeterone and its pharmacologically active metabolite - 3-keto-Δ4-galeterone (D4G) - with one of the key enzymes of corticoSteroid biosynthesis - Steroid 21-Monooxygenase (CYP21A2). It was shown by absorption spectroscopy that both compounds induce type I spectral changes of CYP21A2. Spectral dissociation constants (KS ) of complexes of CYP21A2 with galeterone or D4G were calculated as 3.1 ± 0.7 μm and 4.6 ± 0.4 μm, respectively. It was predicted by molecular docking that both ligands similarly bind to the active site of CYP21A2. We have revealed using reconstituted Monooxygenase system that galeterone is a competitive inhibitor of CYP21A2 with the inhibition constant (Ki ) value of 12 ± 3 μm, while D4G at the concentrations of 10 and 25 μm does not inhibit the enzyme. Summarizing, based on the in vitro analyses we detected inhibition of CYP21A2 by galeterone and lack of the influence of D4G on this enzyme.
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estimation of the inhibiting impact of abiraterone d4a metabolite on human Steroid 21 Monooxygenase cyp21a2
Steroids, 2020Co-Authors: Rami A Masamrekh, Tatiana A Filippova, Yaraslau I Haurychenka, Kirill Shcherbakov, A V Veselovsky, N V Strushkevich, T V Shkel, Andrei A Gilep, S A Usanov, Victoria V ShumyantsevaAbstract:Abstract Abiraterone D4A metabolite, the product of 3β-hydroxySteroid dehydrogenase activity toward abiraterone, may serve as a potential antitumor agent for the treatment of prostate cancer. The main adverse effect of abiraterone is the disruption of corticoSteroid biosynthesis, and the more pharmacologically active abiraterone D4A metabolite may have the same issues. We therefore estimated the inhibiting impact of the abiraterone D4A metabolite on one of the key corticoSteroidogenic enzymes – human Steroid 21-Monooxygenase (CYP21A2). Molecular docking of D4A into the active site of CYP21A2 has been predicted to be similar to abiraterone binding with the enzyme. Abiraterone D4A metabolite, similar to abiraterone, induces type II spectral changes of CYP21A2. The spectral dissociation constant for the abiraterone D4A metabolite-CYP21A2 complex was calculated as 3.4 ± 0.5 μM. Abiraterone D4A metabolite demonstrates competitive/mixed type CYP21A2 inhibition with an inhibitory constant of 1.8 ± 0.8 μM, as obtained by Dixon plot. These results make it possible to predict the adverse effects of the new perspective candidate compound for antitumor therapy.
Yaraslau I Haurychenka - One of the best experts on this subject based on the ideXlab platform.
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estimation of the inhibiting impact of abiraterone d4a metabolite on human Steroid 21 Monooxygenase cyp21a2
Steroids, 2020Co-Authors: Rami A Masamrekh, Tatiana A Filippova, Yaraslau I Haurychenka, Kirill Shcherbakov, A V Veselovsky, N V Strushkevich, T V Shkel, Andrei A Gilep, S A Usanov, Victoria V ShumyantsevaAbstract:Abstract Abiraterone D4A metabolite, the product of 3β-hydroxySteroid dehydrogenase activity toward abiraterone, may serve as a potential antitumor agent for the treatment of prostate cancer. The main adverse effect of abiraterone is the disruption of corticoSteroid biosynthesis, and the more pharmacologically active abiraterone D4A metabolite may have the same issues. We therefore estimated the inhibiting impact of the abiraterone D4A metabolite on one of the key corticoSteroidogenic enzymes – human Steroid 21-Monooxygenase (CYP21A2). Molecular docking of D4A into the active site of CYP21A2 has been predicted to be similar to abiraterone binding with the enzyme. Abiraterone D4A metabolite, similar to abiraterone, induces type II spectral changes of CYP21A2. The spectral dissociation constant for the abiraterone D4A metabolite-CYP21A2 complex was calculated as 3.4 ± 0.5 μM. Abiraterone D4A metabolite demonstrates competitive/mixed type CYP21A2 inhibition with an inhibitory constant of 1.8 ± 0.8 μM, as obtained by Dixon plot. These results make it possible to predict the adverse effects of the new perspective candidate compound for antitumor therapy.