ArticleJournal of medicinal chemistry2018
Structure-Based Design of Inhibitors with Improved Selectivity for Steroidogenic Cytochrome P450 17A1 over Cytochrome P450 21A2.
Article in Journal of medicinal chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 35 citations in OpenAlex.
- Synthesis, Molecular Modeling and Assessment of Anticancer Activity of New Potential CYP17A1 Inhibitors.Molecules (Basel, Switzerland) · 2026Article
- Dihydrotanshinone as a Natural Product-Based CYP17A1 Lyase Inhibitor for Hyperandrogenic Disorders.Biomolecules · 2026Article
- Computational Investigation of the Therapeutic Potential ofInternational journal of molecular sciences · 2024Article
- Abiraterone and Galeterone, Powerful Tools Against Prostate Cancer: Present and Perspective.Pharmaceutics · 2024Review
- Steroidogenic cytochrome P450 enzymes as drug target.Toxicological research · 2024Review
- Cytochrome P450 Enzymes as Drug Targets in Human Disease.Drug metabolism and disposition: the biological fate of chemicals · 2024Review
- Characterization of Potential Target Genes of Borneol in Increasing Trastuzumab Sensitivity in HER2+ Trastuzumab-Resistant Breast Cancer: Bioinformatics and In Vitro Studies.Asian Pacific journal of cancer prevention : APJCP · 2024Article
- Exploring the Potential of Sulfur Moieties in Compounds Inhibiting Steroidogenesis.Biomolecules · 2023Article
- Allosteric modulation of cytochrome P450 enzymes by the NADPH cytochrome P450 reductase FMN-containing domain.The Journal of biological chemistry · 2023Article
- Recombinant Technologies Facilitate Drug Metabolism, Pharmacokinetics, and General Biomedical Research.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Non-steroidal CYP17A1 Inhibitors: Discovery and Assessment.Journal of medicinal chemistry · 2023Review
- Generation of human steroidogenic cytochrome P450 enzymes for structural and functional characterization.Methods in enzymology · 2023Article
- Steroid 17α-hydroxylase/17, 20-lyase (cytochrome P450 17A1).Methods in enzymology · 2023Article
- Synthesis and Structure-Activity Relationships of Novel Non-Steroidal CYP17A1 Inhibitors as Potential Prostate Cancer Agents.Biomolecules · 2022Article
- Steroidogenic cytochrome P450 17A1 structure and function.Molecular and cellular endocrinology · 2021Review
- Discovery of Novel Non-Steroidal Cytochrome P450 17A1 Inhibitors as Potential Prostate Cancer Agents.International journal of molecular sciences · 2020Article
- Conformational selection dominates binding of steroids to human cytochrome P450 17A1.The Journal of biological chemistry · 2019Article
- Endogenous insertion of non-native metalloporphyrins into human membrane cytochrome P450 enzymes.The Journal of biological chemistry · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Inhibition of androgen biosynthesis is clinically effective for treating androgen-responsive prostate cancer. Abiraterone is a clinical first-in-class inhibitor of cytochrome P450 17A1 (CYP17A1) required for androgen biosynthesis. However, abiraterone also causes hypertension, hypokalemia, and edema, likely due in part to off-target inhibition of another steroidogenic cytochrome P450, CYP21A2. Abiraterone analogs were designed based on structural evidence that B-ring substituents may favorably interact with polar residues in binding CYP17A1 and sterically clash with residues in the CYP21A2 active site. The best analogs increased selectivity of CYP17A1 inhibition up to 84-fold compared with 6.6-fold for abiraterone. Cocrystallization with CYP17A1 validated the intended new contacts with CYP17A1 active site residues. Docking these analogs into CYP21A2 identified steric clashes that likely underlie decreased binding and CYP21A2 inhibition. Overall, these analogs may offer a clinical advantage in the form of reduced side effects.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.