FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2898648097> ?p ?o ?g. }

• W2898648097 abstract "Colorectal cancer is the third most common cancer worldwide; and in 40% of all cases, KRAS4b-activating mutations occur. KRAS4b is transported by phosphodiesterase-6δ (PDEδ) to the plasma membrane, where it gets activated. PDEδ downregulation prevents redistribution and activation of KRAS4b. Thus, targeting the KRAS4b-PDEδ complex is a treatment strategy for colorectal cancer.Using docking and molecular dynamics simulations coupled to molecular mechanics, the generalized born model and solvent accessibility (MMGBSA) approach to explore protein-ligand stability, we found that the compound ((2S)-N-(2,5-diclorofenil)-2-[(3,4-dimetoxifenil)metilamino]-propanamida), termed C19, bound and stabilized the KRAS4b-PDEδ complex. We investigated whether C19 decreases the viability and proliferation of colorectal cancer cells, in addition to knowing the type of cell death that it causes and if C19 decreases the activation of KRAS4b and their effectors.C19 showed high cytotoxicity in the colorectal cancer cell lines HCT116 and LoVo, with a stronger effect in KRAS-dependent LoVo cells. Importantly, C19 significantly decreased tumor size in a xenograft mouse model and showed lower side effects than 5-fluorouracil that is currently used as colorectal cancer treatment.Mechanistically, the cytotoxic effect was due to increased apoptosis of tumor cells and decreased phosphorylation of Erk and Akt. Therefore, our results suggest that C19 may serve as a promising new treatment for colorectal cancer." @default.
• W2898648097 created "2018-11-09" @default.
• W2898648097 creator A5001750465 @default.
• W2898648097 creator A5003550597 @default.
• W2898648097 creator A5022212872 @default.
• W2898648097 creator A5041724997 @default.
• W2898648097 creator A5042613793 @default.
• W2898648097 creator A5054642083 @default.
• W2898648097 creator A5057808245 @default.
• W2898648097 creator A5078760270 @default.
• W2898648097 creator A5083842021 @default.
• W2898648097 creator A5088103395 @default.
• W2898648097 creator A5088458670 @default.
• W2898648097 creator A5090499237 @default.
• W2898648097 date "2018-11-01" @default.
• W2898648097 modified "2023-10-18" @default.
• W2898648097 title "The small organic molecule C19 binds and strengthens the KRAS4b-PDEδ complex and inhibits growth of colorectal cancer cells in vitro and in vivo" @default.
• W2898648097 cites W1018331845 @default.
• W2898648097 cites W1757407923 @default.
• W2898648097 cites W1940641879 @default.
• W2898648097 cites W1942560962 @default.
• W2898648097 cites W1968984443 @default.
• W2898648097 cites W1975580333 @default.
• W2898648097 cites W1976499671 @default.
• W2898648097 cites W1982440685 @default.
• W2898648097 cites W2004774286 @default.
• W2898648097 cites W2025956946 @default.
• W2898648097 cites W2035266068 @default.
• W2898648097 cites W2036867510 @default.
• W2898648097 cites W2043282329 @default.
• W2898648097 cites W2045907809 @default.
• W2898648097 cites W2067174909 @default.
• W2898648097 cites W2069123478 @default.
• W2898648097 cites W2069537707 @default.
• W2898648097 cites W2078965068 @default.
• W2898648097 cites W2080719056 @default.
• W2898648097 cites W2081990599 @default.
• W2898648097 cites W2099302886 @default.
• W2898648097 cites W2103636724 @default.
• W2898648097 cites W2105668062 @default.
• W2898648097 cites W2118233996 @default.
• W2898648097 cites W2128339707 @default.
• W2898648097 cites W2146037607 @default.
• W2898648097 cites W2147993766 @default.
• W2898648097 cites W2151457918 @default.
• W2898648097 cites W2152187133 @default.
• W2898648097 cites W2157281740 @default.
• W2898648097 cites W2158289038 @default.
• W2898648097 cites W2164270482 @default.
• W2898648097 cites W2216133246 @default.
• W2898648097 cites W2538983301 @default.
• W2898648097 cites W2790733828 @default.
• W2898648097 cites W2791543036 @default.
• W2898648097 cites W2908006499 @default.
• W2898648097 cites W4245447704 @default.
• W2898648097 doi "https://doi.org/10.1186/s12885-018-4968-3" @default.
• W2898648097 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6211466" @default.
• W2898648097 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30382908" @default.
• W2898648097 hasPublicationYear "2018" @default.
• W2898648097 type Work @default.
• W2898648097 sameAs 2898648097 @default.
• W2898648097 citedByCount "12" @default.
• W2898648097 countsByYear W28986480972019 @default.
• W2898648097 countsByYear W28986480972020 @default.
• W2898648097 countsByYear W28986480972021 @default.
• W2898648097 countsByYear W28986480972022 @default.
• W2898648097 countsByYear W28986480972023 @default.
• W2898648097 crossrefType "journal-article" @default.
• W2898648097 hasAuthorship W2898648097A5001750465 @default.
• W2898648097 hasAuthorship W2898648097A5003550597 @default.
• W2898648097 hasAuthorship W2898648097A5022212872 @default.
• W2898648097 hasAuthorship W2898648097A5041724997 @default.
• W2898648097 hasAuthorship W2898648097A5042613793 @default.
• W2898648097 hasAuthorship W2898648097A5054642083 @default.
• W2898648097 hasAuthorship W2898648097A5057808245 @default.
• W2898648097 hasAuthorship W2898648097A5078760270 @default.
• W2898648097 hasAuthorship W2898648097A5083842021 @default.
• W2898648097 hasAuthorship W2898648097A5088103395 @default.
• W2898648097 hasAuthorship W2898648097A5088458670 @default.
• W2898648097 hasAuthorship W2898648097A5090499237 @default.
• W2898648097 hasBestOaLocation W28986480971 @default.
• W2898648097 hasConcept C121608353 @default.
• W2898648097 hasConcept C126322002 @default.
• W2898648097 hasConcept C185592680 @default.
• W2898648097 hasConcept C190283241 @default.
• W2898648097 hasConcept C2780140570 @default.
• W2898648097 hasConcept C2781187634 @default.
• W2898648097 hasConcept C502942594 @default.
• W2898648097 hasConcept C526805850 @default.
• W2898648097 hasConcept C55493867 @default.
• W2898648097 hasConcept C71924100 @default.
• W2898648097 hasConcept C75217442 @default.
• W2898648097 hasConcept C96232424 @default.
• W2898648097 hasConceptScore W2898648097C121608353 @default.
• W2898648097 hasConceptScore W2898648097C126322002 @default.
• W2898648097 hasConceptScore W2898648097C185592680 @default.
• W2898648097 hasConceptScore W2898648097C190283241 @default.
• W2898648097 hasConceptScore W2898648097C2780140570 @default.
• W2898648097 hasConceptScore W2898648097C2781187634 @default.
• W2898648097 hasConceptScore W2898648097C502942594 @default.

• next