FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2078412962> ?p ?o ?g. }

• W2078412962 endingPage "3927" @default.
• W2078412962 startingPage "3905" @default.
• W2078412962 abstract "High throughput screening identified 2-acetamido-thiazolylthio acetic ester 1 as an inhibitor of cyclin-dependent kinase 2 (CDK2). Because this compound is inactive in cells and unstable in plasma, we have stabilized it to metabolic hydrolysis by replacing the ester moiety with a 5-ethyl-substituted oxazole as in compound 14. Combinatorial and parallel synthesis provided a rapid analysis of the structure-activity relationship (SAR) for these inhibitors of CDK2, and over 100 analogues with IC(50) values in the 1-10 nM range were rapidly prepared. The X-ray crystallographic data of the inhibitors bound to the active site of CDK2 protein provided insight into the binding modes of these inhibitors, and the SAR of this series of analogues was rationalized. Many of these analogues displayed potent and broad spectrum antiproliferative activity across a panel of tumor cell lines in vitro. In addition, A2780 ovarian carcinoma cells undergo rapid apoptosis following exposure to CDK2 inhibitors of this class. Mechanism of action studies have confirmed that the phosphorylation of CDK2 substrates such as RB, histone H1, and DNA polymerase alpha (p70 subunit) is reduced in the presence of compound 14. Further optimization led to compounds such as water soluble 45, which possesses a favorable pharmacokinetic profile in mice and demonstrates significant antitumor activity in vivo in several murine and human models, including an engineered murine mammary tumor that overexpresses cyclin E, the coactivator of CDK2." @default.
• W2078412962 created "2016-06-24" @default.
• W2078412962 creator A5004534725 @default.
• W2078412962 creator A5006622999 @default.
• W2078412962 creator A5010833702 @default.
• W2078412962 creator A5019691277 @default.
• W2078412962 creator A5019693161 @default.
• W2078412962 creator A5027980862 @default.
• W2078412962 creator A5032174758 @default.
• W2078412962 creator A5033444293 @default.
• W2078412962 creator A5035004504 @default.
• W2078412962 creator A5035465180 @default.
• W2078412962 creator A5038001122 @default.
• W2078412962 creator A5042779366 @default.
• W2078412962 creator A5043856025 @default.
• W2078412962 creator A5047105106 @default.
• W2078412962 creator A5048066355 @default.
• W2078412962 creator A5052378655 @default.
• W2078412962 creator A5053510463 @default.
• W2078412962 creator A5059314093 @default.
• W2078412962 creator A5059873188 @default.
• W2078412962 creator A5068910965 @default.
• W2078412962 creator A5071652091 @default.
• W2078412962 creator A5075615241 @default.
• W2078412962 creator A5077321383 @default.
• W2078412962 creator A5080445936 @default.
• W2078412962 creator A5082862286 @default.
• W2078412962 creator A5083385424 @default.
• W2078412962 creator A5084736793 @default.
• W2078412962 creator A5086704967 @default.
• W2078412962 creator A5087570789 @default.
• W2078412962 creator A5087922909 @default.
• W2078412962 date "2002-08-01" @default.
• W2078412962 modified "2023-10-10" @default.
• W2078412962 title "Discovery of Aminothiazole Inhibitors of Cyclin-Dependent Kinase 2: Synthesis, X-ray Crystallographic Analysis, and Biological Activities" @default.
• W2078412962 cites W1777669545 @default.
• W2078412962 cites W1868874850 @default.
• W2078412962 cites W1969939692 @default.
• W2078412962 cites W1973006412 @default.
• W2078412962 cites W1983348452 @default.
• W2078412962 cites W1984226397 @default.
• W2078412962 cites W1985075123 @default.
• W2078412962 cites W1985844240 @default.
• W2078412962 cites W1986264978 @default.
• W2078412962 cites W1988533642 @default.
• W2078412962 cites W1994066190 @default.
• W2078412962 cites W1995425358 @default.
• W2078412962 cites W1997073961 @default.
• W2078412962 cites W2019479941 @default.
• W2078412962 cites W2028943451 @default.
• W2078412962 cites W2029080338 @default.
• W2078412962 cites W2030461484 @default.
• W2078412962 cites W2049830830 @default.
• W2078412962 cites W2059956556 @default.
• W2078412962 cites W2064670731 @default.
• W2078412962 cites W2084147994 @default.
• W2078412962 cites W2089528428 @default.
• W2078412962 cites W2108929767 @default.
• W2078412962 cites W2109458089 @default.
• W2078412962 cites W2117263757 @default.
• W2078412962 cites W2117650991 @default.
• W2078412962 cites W4230681416 @default.
• W2078412962 cites W2011247050 @default.
• W2078412962 doi "https://doi.org/10.1021/jm0201520" @default.
• W2078412962 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/12190313" @default.
• W2078412962 hasPublicationYear "2002" @default.
• W2078412962 type Work @default.
• W2078412962 sameAs 2078412962 @default.
• W2078412962 citedByCount "144" @default.
• W2078412962 countsByYear W20784129622012 @default.
• W2078412962 countsByYear W20784129622013 @default.
• W2078412962 countsByYear W20784129622014 @default.
• W2078412962 countsByYear W20784129622015 @default.
• W2078412962 countsByYear W20784129622016 @default.
• W2078412962 countsByYear W20784129622017 @default.
• W2078412962 countsByYear W20784129622018 @default.
• W2078412962 countsByYear W20784129622019 @default.
• W2078412962 countsByYear W20784129622020 @default.
• W2078412962 countsByYear W20784129622021 @default.
• W2078412962 countsByYear W20784129622022 @default.
• W2078412962 crossrefType "journal-article" @default.
• W2078412962 hasAuthorship W2078412962A5004534725 @default.
• W2078412962 hasAuthorship W2078412962A5006622999 @default.
• W2078412962 hasAuthorship W2078412962A5010833702 @default.
• W2078412962 hasAuthorship W2078412962A5019691277 @default.
• W2078412962 hasAuthorship W2078412962A5019693161 @default.
• W2078412962 hasAuthorship W2078412962A5027980862 @default.
• W2078412962 hasAuthorship W2078412962A5032174758 @default.
• W2078412962 hasAuthorship W2078412962A5033444293 @default.
• W2078412962 hasAuthorship W2078412962A5035004504 @default.
• W2078412962 hasAuthorship W2078412962A5035465180 @default.
• W2078412962 hasAuthorship W2078412962A5038001122 @default.
• W2078412962 hasAuthorship W2078412962A5042779366 @default.
• W2078412962 hasAuthorship W2078412962A5043856025 @default.
• W2078412962 hasAuthorship W2078412962A5047105106 @default.
• W2078412962 hasAuthorship W2078412962A5048066355 @default.
• W2078412962 hasAuthorship W2078412962A5052378655 @default.
• W2078412962 hasAuthorship W2078412962A5053510463 @default.

• next