Journal: Drug metabolism and disposition: the biological fate of chemicals

Article Title: Contribution of UGT Enzymes to Human Drug Metabolism Stereoselectivity: A Case Study of Medetomidine, RO5263397, Propranolol, and Testosterone.

doi: 10.1124/dmd.122.001024

Figure Lengend Snippet: Fig. 1. (A) Molecular structures of the three enantiopairs and the epimers testosterone and epitestosterone tested in this work. The arrow indicates the site of metabo- lism, and the asterisk indicates the location of the relevant stereocenter. For the epimers, the asterisk highlights the unique different chiral center between testosterone and epitestosterone. (B) Schematic representation of the experimental workflow and the in vitro–in vivo clearance extrapolation. CES, Carboxylesterase; FMO, Flavin- containing monooxygenase.

Article Snippet: Alamethicin and UDP glucuronic acid (UDPGA) were purchased from Sigma-Aldrich (St. Louis, MO). (-)-(R)-Medetomidine (levomedetomidine), (-)-(R)-propranolol, (1)-(S)-propranolol, testosterone, and epitestosterone were purchased from Toronto Research Chemicals (North York, Ontario, Canada).

Techniques: In Vitro, In Vivo

Journal: Drug metabolism and disposition: the biological fate of chemicals

Article Title: Contribution of UGT Enzymes to Human Drug Metabolism Stereoselectivity: A Case Study of Medetomidine, RO5263397, Propranolol, and Testosterone.

doi: 10.1124/dmd.122.001024

Figure Lengend Snippet: Fig. 2. UGT-mediated drug depletion and metabolite formation of medetomidine, RO5263397, propranolol, and testosterone and their enantiomers by pooled HLM. Assessment of drug depletion (lefthand graphs) and glucu- ronide metabolite formation (righthand graphs) for enantio- pairs levo-/dex-medetomidine, RO5263397/RO5263396, S-/R-propranolol, and epitestosterone/testosterone by pooled human liver microsomes supplemented with UDPGA. Medetomidine metabolite appearance profiles show sum of glucuronide metabolite signals. Data are mean ± S.D. from triplicate incubations performed in a preliminary experiment in the absence of BSA. Exponential decay profile fitted to drug depletion data, and hyperbolic me- tabolite appearance profile fitted to glucuronide forma- tion data. Red profiles/filled circles, faster metabolized enantiomer; black profiles/filled diamonds, slower me- tabolized enantiomer.

Article Snippet: Alamethicin and UDP glucuronic acid (UDPGA) were purchased from Sigma-Aldrich (St. Louis, MO). (-)-(R)-Medetomidine (levomedetomidine), (-)-(R)-propranolol, (1)-(S)-propranolol, testosterone, and epitestosterone were purchased from Toronto Research Chemicals (North York, Ontario, Canada).

Techniques:

Journal: Drug metabolism and disposition: the biological fate of chemicals

Article Title: Contribution of UGT Enzymes to Human Drug Metabolism Stereoselectivity: A Case Study of Medetomidine, RO5263397, Propranolol, and Testosterone.

doi: 10.1124/dmd.122.001024

Figure Lengend Snippet: Fig. 5. Molecular overlapping of each pair of stereoisomers in unconstrained and constrained (site of metabolism forced to overlap) conditions: Unconstrained and constrained molecular overlapping of each pair of stereoisomers. In red are shown the higher UGT turnover enantiomers (RO5263397, levomedetomidine, S- propranolol, and epitestosterone) and shown in black are the lower UGT turnover enantiomers RO5263396, dexmedetomidine, R-propranolol, and testosterone. Ar- rows and asterisks indicate the sites of conjugation (in the constrained poses) and the chiral centers, respectively. For the epimers testosterone and epitestosterone the asterisk represents only the unique different chiral center.

Article Snippet: Alamethicin and UDP glucuronic acid (UDPGA) were purchased from Sigma-Aldrich (St. Louis, MO). (-)-(R)-Medetomidine (levomedetomidine), (-)-(R)-propranolol, (1)-(S)-propranolol, testosterone, and epitestosterone were purchased from Toronto Research Chemicals (North York, Ontario, Canada).

Techniques: Conjugation Assay

Journal: Molecules

Article Title: New Insights into the Metabolism of Methyltestosterone and Metandienone: Detection of Novel A-Ring Reduced Metabolites

doi: 10.3390/molecules26051354

Figure Lengend Snippet: Reaction scheme for 17α-hydroxymethyl-17β-methyl-18-nor-5ξ-androst-13-en-3ξ-ol steroids.

Article Snippet: 17β-Methyltestosterone (epi-MT, 9 ) was obtained from Santa Cruz Biotechnology (Heidelberg, Germany).

Techniques:

Journal: Molecules

Article Title: New Insights into the Metabolism of Methyltestosterone and Metandienone: Detection of Novel A-Ring Reduced Metabolites

doi: 10.3390/molecules26051354

Figure Lengend Snippet: Mass spectrum (GC-EI-QTOF-MS, 70 eV) of 17α-hydroxymethyl-17β-methyl-18-nor-5β-androst-13-en-3α-ol ( 8 ), bis- trimethylsilyl) (TMS (x-axis: m / z ; y-axis: relative abundance).

Article Snippet: 17β-Methyltestosterone (epi-MT, 9 ) was obtained from Santa Cruz Biotechnology (Heidelberg, Germany).

Techniques:

Journal: Molecules

Article Title: New Insights into the Metabolism of Methyltestosterone and Metandienone: Detection of Novel A-Ring Reduced Metabolites

doi: 10.3390/molecules26051354

Figure Lengend Snippet: Retention times (GC-QQQ-MS), molecular ions (M •+ ) in low electron ionization (LEI, 20 eV), and mass difference to exact mass ( m / z ther 448.3187, C 26 H 48 O 2 Si 2 +• ) of diasteromeric 17α-hydroxymethyl-17β-methyl-18-nor-5ξ-androst-13-en-3ξ-ols as per-TMS derivatives.

Article Snippet: 17β-Methyltestosterone (epi-MT, 9 ) was obtained from Santa Cruz Biotechnology (Heidelberg, Germany).

Techniques:

Journal: Molecules

Article Title: New Insights into the Metabolism of Methyltestosterone and Metandienone: Detection of Novel A-Ring Reduced Metabolites

doi: 10.3390/molecules26051354

Figure Lengend Snippet: 1 H and 13 C NMR spectral data of 17α-hydroxymethyl-17β-methyl-18-nor-5β-androst-13-en-3α-ol ( 8 ) and 17α-hydroxymethyl-17β-methyl-18-nor-5α-androst-13-en-3α-ol ( 8a ). Multiplicity of signals indicated as singlet (s), doublet (d).

Article Snippet: 17β-Methyltestosterone (epi-MT, 9 ) was obtained from Santa Cruz Biotechnology (Heidelberg, Germany).

Techniques:

Journal: Molecules

Article Title: New Insights into the Metabolism of Methyltestosterone and Metandienone: Detection of Novel A-Ring Reduced Metabolites

doi: 10.3390/molecules26051354

Figure Lengend Snippet: Synthesis route for 17β-methyl-5β-androstane-3α,17α-diol ( 11 ).

Article Snippet: 17β-Methyltestosterone (epi-MT, 9 ) was obtained from Santa Cruz Biotechnology (Heidelberg, Germany).

Techniques:

Journal: Molecules

Article Title: New Insights into the Metabolism of Methyltestosterone and Metandienone: Detection of Novel A-Ring Reduced Metabolites

doi: 10.3390/molecules26051354

Figure Lengend Snippet: Mass spectrum (GC-EI-QTOF-MS, 70 eV) of 17β-methyl-5β-androstane-3α,17α-diol ( 11 ), bis TMS (x-axis: m / z ; y-axis: relative abundance).

Article Snippet: 17β-Methyltestosterone (epi-MT, 9 ) was obtained from Santa Cruz Biotechnology (Heidelberg, Germany).

Techniques:

Journal: Molecules

Article Title: New Insights into the Metabolism of Methyltestosterone and Metandienone: Detection of Novel A-Ring Reduced Metabolites

doi: 10.3390/molecules26051354

Figure Lengend Snippet: Retention times (GC-QQQ-MS) and ion transitions of currently targeted metabolites in anti-doping analysis.

Article Snippet: 17β-Methyltestosterone (epi-MT, 9 ) was obtained from Santa Cruz Biotechnology (Heidelberg, Germany).

Techniques:

Journal: Molecules

Article Title: New Insights into the Metabolism of Methyltestosterone and Metandienone: Detection of Novel A-Ring Reduced Metabolites

doi: 10.3390/molecules26051354

Figure Lengend Snippet: Proposed metabolism of methyltestosterone (black, 18 ) and metandienone (red, 12 ) to the found metabolites 17α-hydroxymethyl-17β-methyl-18-nor-5β-androst-13-en-3α-ol ( 8 ), 17α-hydroxymethyl-17β-methyl-18-nor-5α-androst-13-en-3α-ol ( 8a ), and 17β-methyl-5β-androstane-3α,17α-diol ( 11 ) except last step of metandienone. The question marks represent reactions whose enzymes have not been elucidated yet.

Article Snippet: 17β-Methyltestosterone (epi-MT, 9 ) was obtained from Santa Cruz Biotechnology (Heidelberg, Germany).

Techniques: