FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1968973920> ?p ?o ?g. }

• W1968973920 endingPage "119" @default.
• W1968973920 startingPage "116" @default.
• W1968973920 abstract "Cytochrome P450 17A1 (also known as CYP17A1 and cytochrome P450c17) catalyses the biosynthesis of androgens in humans. As prostate cancer cells proliferate in response to androgen steroids, CYP17A1 inhibition is a new strategy to prevent androgen synthesis and treat lethal metastatic castration-resistant prostate cancer, but drug development has been hampered by lack of information regarding the structure of CYP17A1. Here we report X-ray crystal structures of CYP17A1, which were obtained in the presence of either abiraterone, a first-in-class steroidal inhibitor recently approved by the US Food and Drug Administration for late-stage prostate cancer, or TOK-001, an inhibitor that is currently undergoing clinical trials. Both of these inhibitors bind the haem iron, forming a 60° angle above the haem plane and packing against the central I helix with the 3β-OH interacting with aspargine 202 in the F helix. Notably, this binding mode differs substantially from those that are predicted by homology models and from steroids in other cytochrome P450 enzymes with known structures, and some features of this binding mode are more similar to steroid receptors. Whereas the overall structure of CYP17A1 provides a rationale for understanding many mutations that are found in patients with steroidogenic diseases, the active site reveals multiple steric and hydrogen bonding features that will facilitate a better understanding of the enzyme's dual hydroxylase and lyase catalytic capabilities and assist in rational drug design. Specifically, structure-based design is expected to aid development of inhibitors that bind only CYP17A1 and solely inhibit its androgen-generating lyase activity to improve treatment of prostate and other hormone-responsive cancers." @default.
• W1968973920 created "2016-06-24" @default.
• W1968973920 creator A5012368572 @default.
• W1968973920 creator A5087917496 @default.
• W1968973920 date "2012-01-22" @default.
• W1968973920 modified "2023-10-13" @default.
• W1968973920 title "Structures of cytochrome P450 17A1 with prostate cancer drugs abiraterone and TOK-001" @default.
• W1968973920 cites W1534922012 @default.
• W1968973920 cites W1579297624 @default.
• W1968973920 cites W1969058680 @default.
• W1968973920 cites W1969952491 @default.
• W1968973920 cites W1972490547 @default.
• W1968973920 cites W1974809008 @default.
• W1968973920 cites W1986191025 @default.
• W1968973920 cites W1991643603 @default.
• W1968973920 cites W2001641653 @default.
• W1968973920 cites W2004097808 @default.
• W1968973920 cites W2008145170 @default.
• W1968973920 cites W2009171847 @default.
• W1968973920 cites W2014086569 @default.
• W1968973920 cites W2018684250 @default.
• W1968973920 cites W2028064827 @default.
• W1968973920 cites W2036268251 @default.
• W1968973920 cites W2038840577 @default.
• W1968973920 cites W2042003292 @default.
• W1968973920 cites W2049680469 @default.
• W1968973920 cites W2052420006 @default.
• W1968973920 cites W2053530773 @default.
• W1968973920 cites W2055131068 @default.
• W1968973920 cites W2061577482 @default.
• W1968973920 cites W2066072430 @default.
• W1968973920 cites W2069050716 @default.
• W1968973920 cites W2079750211 @default.
• W1968973920 cites W2088933990 @default.
• W1968973920 cites W2103133230 @default.
• W1968973920 cites W2103794058 @default.
• W1968973920 cites W2109785424 @default.
• W1968973920 cites W2110534364 @default.
• W1968973920 cites W2118818078 @default.
• W1968973920 cites W2126733133 @default.
• W1968973920 cites W2130215507 @default.
• W1968973920 cites W2144081223 @default.
• W1968973920 cites W2149044745 @default.
• W1968973920 cites W2167878233 @default.
• W1968973920 cites W2170544517 @default.
• W1968973920 cites W4234452258 @default.
• W1968973920 doi "https://doi.org/10.1038/nature10743" @default.
• W1968973920 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3271139" @default.
• W1968973920 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22266943" @default.
• W1968973920 hasPublicationYear "2012" @default.
• W1968973920 type Work @default.
• W1968973920 sameAs 1968973920 @default.
• W1968973920 citedByCount "271" @default.
• W1968973920 countsByYear W19689739202012 @default.
• W1968973920 countsByYear W19689739202013 @default.
• W1968973920 countsByYear W19689739202014 @default.
• W1968973920 countsByYear W19689739202015 @default.
• W1968973920 countsByYear W19689739202016 @default.
• W1968973920 countsByYear W19689739202017 @default.
• W1968973920 countsByYear W19689739202018 @default.
• W1968973920 countsByYear W19689739202019 @default.
• W1968973920 countsByYear W19689739202020 @default.
• W1968973920 countsByYear W19689739202021 @default.
• W1968973920 countsByYear W19689739202022 @default.
• W1968973920 countsByYear W19689739202023 @default.
• W1968973920 crossrefType "journal-article" @default.
• W1968973920 hasAuthorship W1968973920A5012368572 @default.
• W1968973920 hasAuthorship W1968973920A5087917496 @default.
• W1968973920 hasBestOaLocation W19689739202 @default.
• W1968973920 hasConcept C121608353 @default.
• W1968973920 hasConcept C126322002 @default.
• W1968973920 hasConcept C142716871 @default.
• W1968973920 hasConcept C181199279 @default.
• W1968973920 hasConcept C185592680 @default.
• W1968973920 hasConcept C2775832370 @default.
• W1968973920 hasConcept C2777899217 @default.
• W1968973920 hasConcept C2777911890 @default.
• W1968973920 hasConcept C2780192828 @default.
• W1968973920 hasConcept C502942594 @default.
• W1968973920 hasConcept C526171541 @default.
• W1968973920 hasConcept C55493867 @default.
• W1968973920 hasConcept C61367390 @default.
• W1968973920 hasConcept C71315377 @default.
• W1968973920 hasConcept C71924100 @default.
• W1968973920 hasConcept C98274493 @default.
• W1968973920 hasConceptScore W1968973920C121608353 @default.
• W1968973920 hasConceptScore W1968973920C126322002 @default.
• W1968973920 hasConceptScore W1968973920C142716871 @default.
• W1968973920 hasConceptScore W1968973920C181199279 @default.
• W1968973920 hasConceptScore W1968973920C185592680 @default.
• W1968973920 hasConceptScore W1968973920C2775832370 @default.
• W1968973920 hasConceptScore W1968973920C2777899217 @default.
• W1968973920 hasConceptScore W1968973920C2777911890 @default.
• W1968973920 hasConceptScore W1968973920C2780192828 @default.
• W1968973920 hasConceptScore W1968973920C502942594 @default.
• W1968973920 hasConceptScore W1968973920C526171541 @default.
• W1968973920 hasConceptScore W1968973920C55493867 @default.
• W1968973920 hasConceptScore W1968973920C61367390 @default.

• next