FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2885266495> ?p ?o ?g. }

• W2885266495 endingPage "5236" @default.
• W2885266495 startingPage "5236" @default.
• W2885266495 abstract "Abstract The Androgen Receptor (AR) remains the principal driver of castration-resistant prostate cancer during the transition from a localized to metastatic disease. Most patients initially respond to inhibitors of the AR pathway, but the response is often short-lived. The majority of patients progressing on enzalutamide or abiraterone exhibit genetic alterations in the AR locus, either in the form of amplifications or point mutations in the AR gene. Given these mechanisms of resistance, our goal is to eliminate the AR protein using the PROteolysis TArgeting Chimera (PROTAC) technology. Here we report an orally bioavailable small molecule ARV-110 that leads to ubiquitination and degradation of AR. ARV-110 completely degrades AR in all cell lines tested, with an observed 50% degradation concentration (DC50) &lt; 1 nM. PROTAC-mediated AR degradation suppresses the expression of the AR-target genes PSA and FKBP5, inhibits AR-dependent cell proliferation, and induces potent apoptosis in VCaP cells. ARV-110 degrades clinically relevant mutant AR proteins and retains activity in a high androgen environment. In mouse xenograft studies, greater than 90% AR degradation is observed at a 1 mg/kg PO QD dose. Significant inhibition of tumor growth and AR signaling can be achieved in both an intact and castrate setting. Further, ARV-110 demonstrates in vivo efficacy and reduction of oncogenic Erg protein in a long term, castrate, enzalutamide-resistant VCaP tumor model. DMPK and exploratory toxicology studies show robust oral, dose proportional drug exposure in rodent and non-rodent species. In summary, we report preclinical data on ARV-110, an orally bioavailable androgen receptor PROTAC degrader that demonstrates efficacy in enzalutamide-resistant prostate cancer. Citation Format: Taavi Neklesa, Lawrence B. Snyder, Ryan R. Willard, Nicholas Vitale, Kanak Raina, Jennifer Pizzano, Deborah Gordon, Mark Bookbinder, Jennifer Macaluso, Hanqing Dong, Zheng Liu, Caterina Ferraro, Gan Wang, Jing Wang, Craig M. Crews, John Houston, Andrew P. Crew, Ian Taylor. ARV-110: An androgen receptor PROTAC degrader for prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5236." @default.
• W2885266495 created "2018-08-22" @default.
• W2885266495 creator A5000114373 @default.
• W2885266495 creator A5000833342 @default.
• W2885266495 creator A5007363139 @default.
• W2885266495 creator A5007702221 @default.
• W2885266495 creator A5016866989 @default.
• W2885266495 creator A5024137095 @default.
• W2885266495 creator A5033072455 @default.
• W2885266495 creator A5034584033 @default.
• W2885266495 creator A5037677450 @default.
• W2885266495 creator A5038644541 @default.
• W2885266495 creator A5038795524 @default.
• W2885266495 creator A5039592991 @default.
• W2885266495 creator A5047533857 @default.
• W2885266495 creator A5050030250 @default.
• W2885266495 creator A5050229370 @default.
• W2885266495 creator A5055366079 @default.
• W2885266495 creator A5064251798 @default.
• W2885266495 creator A5065771969 @default.
• W2885266495 date "2018-07-01" @default.
• W2885266495 modified "2023-09-30" @default.
• W2885266495 title "Abstract 5236: ARV-110: An androgen receptor PROTAC degrader for prostate cancer" @default.
• W2885266495 doi "https://doi.org/10.1158/1538-7445.am2018-5236" @default.
• W2885266495 hasPublicationYear "2018" @default.
• W2885266495 type Work @default.
• W2885266495 sameAs 2885266495 @default.
• W2885266495 citedByCount "33" @default.
• W2885266495 countsByYear W28852664952019 @default.
• W2885266495 countsByYear W28852664952020 @default.
• W2885266495 countsByYear W28852664952021 @default.
• W2885266495 countsByYear W28852664952022 @default.
• W2885266495 countsByYear W28852664952023 @default.
• W2885266495 crossrefType "journal-article" @default.
• W2885266495 hasAuthorship W2885266495A5000114373 @default.
• W2885266495 hasAuthorship W2885266495A5000833342 @default.
• W2885266495 hasAuthorship W2885266495A5007363139 @default.
• W2885266495 hasAuthorship W2885266495A5007702221 @default.
• W2885266495 hasAuthorship W2885266495A5016866989 @default.
• W2885266495 hasAuthorship W2885266495A5024137095 @default.
• W2885266495 hasAuthorship W2885266495A5033072455 @default.
• W2885266495 hasAuthorship W2885266495A5034584033 @default.
• W2885266495 hasAuthorship W2885266495A5037677450 @default.
• W2885266495 hasAuthorship W2885266495A5038644541 @default.
• W2885266495 hasAuthorship W2885266495A5038795524 @default.
• W2885266495 hasAuthorship W2885266495A5039592991 @default.
• W2885266495 hasAuthorship W2885266495A5047533857 @default.
• W2885266495 hasAuthorship W2885266495A5050030250 @default.
• W2885266495 hasAuthorship W2885266495A5050229370 @default.
• W2885266495 hasAuthorship W2885266495A5055366079 @default.
• W2885266495 hasAuthorship W2885266495A5064251798 @default.
• W2885266495 hasAuthorship W2885266495A5065771969 @default.
• W2885266495 hasConcept C121608353 @default.
• W2885266495 hasConcept C126322002 @default.
• W2885266495 hasConcept C134018914 @default.
• W2885266495 hasConcept C185592680 @default.
• W2885266495 hasConcept C207001950 @default.
• W2885266495 hasConcept C2776551883 @default.
• W2885266495 hasConcept C2777911890 @default.
• W2885266495 hasConcept C2779723316 @default.
• W2885266495 hasConcept C2780192828 @default.
• W2885266495 hasConcept C502942594 @default.
• W2885266495 hasConcept C54355233 @default.
• W2885266495 hasConcept C61367390 @default.
• W2885266495 hasConcept C71315377 @default.
• W2885266495 hasConcept C71924100 @default.
• W2885266495 hasConcept C86803240 @default.
• W2885266495 hasConcept C98274493 @default.
• W2885266495 hasConceptScore W2885266495C121608353 @default.
• W2885266495 hasConceptScore W2885266495C126322002 @default.
• W2885266495 hasConceptScore W2885266495C134018914 @default.
• W2885266495 hasConceptScore W2885266495C185592680 @default.
• W2885266495 hasConceptScore W2885266495C207001950 @default.
• W2885266495 hasConceptScore W2885266495C2776551883 @default.
• W2885266495 hasConceptScore W2885266495C2777911890 @default.
• W2885266495 hasConceptScore W2885266495C2779723316 @default.
• W2885266495 hasConceptScore W2885266495C2780192828 @default.
• W2885266495 hasConceptScore W2885266495C502942594 @default.
• W2885266495 hasConceptScore W2885266495C54355233 @default.
• W2885266495 hasConceptScore W2885266495C61367390 @default.
• W2885266495 hasConceptScore W2885266495C71315377 @default.
• W2885266495 hasConceptScore W2885266495C71924100 @default.
• W2885266495 hasConceptScore W2885266495C86803240 @default.
• W2885266495 hasConceptScore W2885266495C98274493 @default.
• W2885266495 hasIssue "13_Supplement" @default.
• W2885266495 hasLocation W28852664951 @default.
• W2885266495 hasOpenAccess W2885266495 @default.
• W2885266495 hasPrimaryLocation W28852664951 @default.
• W2885266495 hasRelatedWork W1511886058 @default.
• W2885266495 hasRelatedWork W2015889618 @default.
• W2885266495 hasRelatedWork W2082788526 @default.
• W2885266495 hasRelatedWork W2442795568 @default.
• W2885266495 hasRelatedWork W2772229485 @default.
• W2885266495 hasRelatedWork W2806156214 @default.
• W2885266495 hasRelatedWork W2948523439 @default.
• W2885266495 hasRelatedWork W2954196387 @default.
• W2885266495 hasRelatedWork W4362477333 @default.
• W2885266495 hasRelatedWork W4362478213 @default.

• next