FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2774173192> ?p ?o ?g. }

• W2774173192 endingPage "28" @default.
• W2774173192 startingPage "1" @default.
• W2774173192 abstract "Glioblastoma multiforme (GBM) is the most common and deadliest of malignant brain tumors in adults. Disease development is associated with dysregulation of the cyclin D-CDK4/6-INK4-Rb pathway, resulting in increased proliferation; thus, CDK4/6 kinase inhibitors are promising candidates for GBM treatment. The recently developed CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib, are effective in subcutaneous glioma models, but their blood-brain barrier (BBB) permeability is poor, limiting drug delivery to the central nervous system. Here, we designed and synthesized a series of novel CDK4/6 inhibitors with favorable BBB permeability for the treatment of GBM. Compound 11 exhibited a favorable pharmacological profile and significant penetration of the BBB with the Kp value of 4.10 and the Kp,uu value of 0.23 in mice after an oral dose of 10 mg/kg. IC50 values for CDK4/cyclin D1 and CDK6/cyclin D3 were 3 nM and 1 nM, respectively. In vivo studies with an orthotopic xenograft mouse model of GBM showed that 11 had tumor growth inhibition values ranging from 62% to 99% for doses ranging from 3.125 to 50 mg/kg, and no significant body weight loss was observed. The increase in life span based on the median survival time of vehicle-treated animals in mice administered a dose of 50 mg/kg was significant at 162% (p < 0.0001). These results suggest that compound 11 is a promising candidate for further investigation as an effective drug for the treatment of GBM." @default.
• W2774173192 created "2017-12-22" @default.
• W2774173192 creator A5013795174 @default.
• W2774173192 creator A5019088881 @default.
• W2774173192 creator A5019399075 @default.
• W2774173192 creator A5020582826 @default.
• W2774173192 creator A5031150615 @default.
• W2774173192 creator A5050645965 @default.
• W2774173192 creator A5060113369 @default.
• W2774173192 date "2018-01-01" @default.
• W2774173192 modified "2023-10-18" @default.
• W2774173192 title "A highly potent CDK4/6 inhibitor was rationally designed to overcome blood brain barrier in gliobastoma therapy" @default.
• W2774173192 cites W1858170452 @default.
• W2774173192 cites W1922104457 @default.
• W2774173192 cites W1964764225 @default.
• W2774173192 cites W1967625949 @default.
• W2774173192 cites W1971513938 @default.
• W2774173192 cites W1974000574 @default.
• W2774173192 cites W1979680515 @default.
• W2774173192 cites W1983091676 @default.
• W2774173192 cites W1985389450 @default.
• W2774173192 cites W1987820290 @default.
• W2774173192 cites W1991054314 @default.
• W2774173192 cites W1991601194 @default.
• W2774173192 cites W1995093170 @default.
• W2774173192 cites W1995632100 @default.
• W2774173192 cites W2002754034 @default.
• W2774173192 cites W2016575780 @default.
• W2774173192 cites W2019513435 @default.
• W2774173192 cites W2025183726 @default.
• W2774173192 cites W2030215451 @default.
• W2774173192 cites W2040827479 @default.
• W2774173192 cites W2046024621 @default.
• W2774173192 cites W2048721919 @default.
• W2774173192 cites W2054626432 @default.
• W2774173192 cites W2057272791 @default.
• W2774173192 cites W2061818721 @default.
• W2774173192 cites W2065669196 @default.
• W2774173192 cites W2069506489 @default.
• W2774173192 cites W2089744178 @default.
• W2774173192 cites W2096287682 @default.
• W2774173192 cites W2105939237 @default.
• W2774173192 cites W2133382697 @default.
• W2774173192 cites W2138800281 @default.
• W2774173192 cites W2141133182 @default.
• W2774173192 cites W2143871691 @default.
• W2774173192 cites W2144135270 @default.
• W2774173192 cites W2145755261 @default.
• W2774173192 cites W2148103576 @default.
• W2774173192 cites W2154542739 @default.
• W2774173192 cites W2154626333 @default.
• W2774173192 cites W2157005154 @default.
• W2774173192 cites W2158080359 @default.
• W2774173192 cites W2171852242 @default.
• W2774173192 cites W2189824412 @default.
• W2774173192 cites W2257348270 @default.
• W2774173192 cites W2317835477 @default.
• W2774173192 cites W2321980425 @default.
• W2774173192 cites W2465158356 @default.
• W2774173192 cites W2588200723 @default.
• W2774173192 doi "https://doi.org/10.1016/j.ejmech.2017.12.003" @default.
• W2774173192 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29247857" @default.
• W2774173192 hasPublicationYear "2018" @default.
• W2774173192 type Work @default.
• W2774173192 sameAs 2774173192 @default.
• W2774173192 citedByCount "35" @default.
• W2774173192 countsByYear W27741731922018 @default.
• W2774173192 countsByYear W27741731922019 @default.
• W2774173192 countsByYear W27741731922020 @default.
• W2774173192 countsByYear W27741731922021 @default.
• W2774173192 countsByYear W27741731922022 @default.
• W2774173192 countsByYear W27741731922023 @default.
• W2774173192 crossrefType "journal-article" @default.
• W2774173192 hasAuthorship W2774173192A5013795174 @default.
• W2774173192 hasAuthorship W2774173192A5019088881 @default.
• W2774173192 hasAuthorship W2774173192A5019399075 @default.
• W2774173192 hasAuthorship W2774173192A5020582826 @default.
• W2774173192 hasAuthorship W2774173192A5031150615 @default.
• W2774173192 hasAuthorship W2774173192A5050645965 @default.
• W2774173192 hasAuthorship W2774173192A5060113369 @default.
• W2774173192 hasConcept C121608353 @default.
• W2774173192 hasConcept C126322002 @default.
• W2774173192 hasConcept C150903083 @default.
• W2774173192 hasConcept C185592680 @default.
• W2774173192 hasConcept C199649820 @default.
• W2774173192 hasConcept C199835354 @default.
• W2774173192 hasConcept C202751555 @default.
• W2774173192 hasConcept C207001950 @default.
• W2774173192 hasConcept C2775930923 @default.
• W2774173192 hasConcept C2777752497 @default.
• W2774173192 hasConcept C2778227246 @default.
• W2774173192 hasConcept C2778402981 @default.
• W2774173192 hasConcept C2779744173 @default.
• W2774173192 hasConcept C29537977 @default.
• W2774173192 hasConcept C502942594 @default.
• W2774173192 hasConcept C529278444 @default.
• W2774173192 hasConcept C530470458 @default.
• W2774173192 hasConcept C55493867 @default.

• next