FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2955178651> ?p ?o ?g. }

• W2955178651 abstract "Background: We had earlier reported a novel therapeutic agent, ERX-11, that modulates estrogen receptor coregulator interactions. For lead optimization, we designed, synthesized and tested over 500 analogs of ERX-11 in multiple models of BC. We also tested this library of compounds for activity against other cancer cell lines both in vitro and in vivo and against primary tumors ex vivo. Methods:In vitro activity was tested using Cell titer glo, MTT, and apoptosis assays.The utility of the ERX analogs in treating therapy resistant ER-positive BC was evaluated using models with acquired resistance (Tamoxifen, Letrozole), and engineered models that express ER mutations. Xenografts were used for testing the utility of ERX analogs in vivo. Primary patient tumor derived explants were used for ex vivo testing of ERX analogs. Results: Our screening studies identified several ERX analogs with potent activity against BC cells. Subtle changes in the ERX analogs appear to have significant ramifications on both their potency against ER+ BC cell lines and against other tumors types. Some analogs like ERX-41 were more potent than ERX-11 in their ability to block the proliferation of multiple ER-positive BC cell lines (IC50 ranging from 20-200nM). Other analogs like ERX-208 showed similar activity as ERX-11 against ER-positive BC cell lines (IC50 ranging from 100-500nM) but had potent activity against ovarian cancer cell lines. Through iterative changes, we have identified leads compounds with significant activity against other cancers, including in gliomas, ovarian and pancreatic cancers. Although all these compounds were designed to better target the ligand binding pocket of ER, these active compounds do not all target ER and appear to target other proteins, including other nuclear receptors. Some compounds for example have activity in ER-negative breast cancers. In several xenograft models, including pancreatic cancer and ER-negative, the activity of the compounds have been confirmed by oral administration of the ERX analog in vivo. We have also validated the activity of these analogs in patient-derived explants cultured ex vivoin multiple tumor types. Conclusions: From our studies to develop a more potent ERX-11 lead analog, we have identified multiple analogs with distinct activities against multiple cancers. While the intended target of these analogs was ER, our library of analogs has potent activity against both ER-positive and ER-negative tumors. In collaboration, we are pursuing further leads in multiple cancers to further delineate the mechanism of action of these various analogs. Citation Format: Ganesh V. Raj, Xihui Liu, Dede Ekoue, Jung-Mo Ahn, Ratna Vadlamudi. Development of potent lead compounds in multiple tumor types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 26." @default.
• W2955178651 created "2019-07-12" @default.
• W2955178651 creator A5010427318 @default.
• W2955178651 creator A5027234036 @default.
• W2955178651 creator A5051435411 @default.
• W2955178651 creator A5053069471 @default.
• W2955178651 creator A5090010000 @default.
• W2955178651 date "2019-07-01" @default.
• W2955178651 modified "2023-09-27" @default.
• W2955178651 title "Abstract 26: Development of potent lead compounds in multiple tumor types" @default.
• W2955178651 doi "https://doi.org/10.1158/1538-7445.sabcs18-26" @default.
• W2955178651 hasPublicationYear "2019" @default.
• W2955178651 type Work @default.
• W2955178651 sameAs 2955178651 @default.
• W2955178651 citedByCount "0" @default.
• W2955178651 crossrefType "proceedings-article" @default.
• W2955178651 hasAuthorship W2955178651A5010427318 @default.
• W2955178651 hasAuthorship W2955178651A5027234036 @default.
• W2955178651 hasAuthorship W2955178651A5051435411 @default.
• W2955178651 hasAuthorship W2955178651A5053069471 @default.
• W2955178651 hasAuthorship W2955178651A5090010000 @default.
• W2955178651 hasConcept C121608353 @default.
• W2955178651 hasConcept C126322002 @default.
• W2955178651 hasConcept C185592680 @default.
• W2955178651 hasConcept C207001950 @default.
• W2955178651 hasConcept C26291073 @default.
• W2955178651 hasConcept C2777176818 @default.
• W2955178651 hasConcept C502942594 @default.
• W2955178651 hasConcept C530470458 @default.
• W2955178651 hasConcept C54355233 @default.
• W2955178651 hasConcept C55493867 @default.
• W2955178651 hasConcept C62112901 @default.
• W2955178651 hasConcept C71924100 @default.
• W2955178651 hasConcept C81885089 @default.
• W2955178651 hasConcept C84606932 @default.
• W2955178651 hasConcept C86803240 @default.
• W2955178651 hasConceptScore W2955178651C121608353 @default.
• W2955178651 hasConceptScore W2955178651C126322002 @default.
• W2955178651 hasConceptScore W2955178651C185592680 @default.
• W2955178651 hasConceptScore W2955178651C207001950 @default.
• W2955178651 hasConceptScore W2955178651C26291073 @default.
• W2955178651 hasConceptScore W2955178651C2777176818 @default.
• W2955178651 hasConceptScore W2955178651C502942594 @default.
• W2955178651 hasConceptScore W2955178651C530470458 @default.
• W2955178651 hasConceptScore W2955178651C54355233 @default.
• W2955178651 hasConceptScore W2955178651C55493867 @default.
• W2955178651 hasConceptScore W2955178651C62112901 @default.
• W2955178651 hasConceptScore W2955178651C71924100 @default.
• W2955178651 hasConceptScore W2955178651C81885089 @default.
• W2955178651 hasConceptScore W2955178651C84606932 @default.
• W2955178651 hasConceptScore W2955178651C86803240 @default.
• W2955178651 hasLocation W29551786511 @default.
• W2955178651 hasOpenAccess W2955178651 @default.
• W2955178651 hasPrimaryLocation W29551786511 @default.
• W2955178651 hasRelatedWork W1591296341 @default.
• W2955178651 hasRelatedWork W1988309517 @default.
• W2955178651 hasRelatedWork W1995290323 @default.
• W2955178651 hasRelatedWork W2036466074 @default.
• W2955178651 hasRelatedWork W2156169240 @default.
• W2955178651 hasRelatedWork W2328051402 @default.
• W2955178651 hasRelatedWork W2505859400 @default.
• W2955178651 hasRelatedWork W2563891994 @default.
• W2955178651 hasRelatedWork W2744198278 @default.
• W2955178651 hasRelatedWork W2751761212 @default.
• W2955178651 hasRelatedWork W2789530016 @default.
• W2955178651 hasRelatedWork W2794167465 @default.
• W2955178651 hasRelatedWork W2892161456 @default.
• W2955178651 hasRelatedWork W2896233108 @default.
• W2955178651 hasRelatedWork W2973053519 @default.
• W2955178651 hasRelatedWork W3128029809 @default.
• W2955178651 hasRelatedWork W3137382674 @default.
• W2955178651 hasRelatedWork W3159314129 @default.
• W2955178651 hasRelatedWork W3178417424 @default.
• W2955178651 hasRelatedWork W595813438 @default.
• W2955178651 isParatext "false" @default.
• W2955178651 isRetracted "false" @default.
• W2955178651 magId "2955178651" @default.
• W2955178651 workType "article" @default.