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Volumn 18, Issue 23, 2008, Pages 6236-6239

Modifications of the isonipecotic acid fragment of SNS-032: Analogs with improved permeability and lower efflux ratio

Author keywords

CDK; Cyclin; Kinase; SNS 032

Indexed keywords

CYCLIN DEPENDENT KINASE 1; CYCLIN DEPENDENT KINASE 2; CYCLIN DEPENDENT KINASE 4; CYCLIN DEPENDENT KINASE 7; CYCLIN DEPENDENT KINASE 9; ISONIPECOTIC ACID; N [5 (5 TERT BUTYL 2 OXAZOLYLMETHYLTHIO) 2 THIAZOLYL]ISONIPECOTAMIDE;

EID: 55549135313     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2008.09.099     Document Type: Article
Times cited : (7)

References (15)
  • 8
    • 53949123761 scopus 로고    scopus 로고
    • Choong, I. C.; Serafimova, I.; Fan, J.; Stockett, D.; Chan, E.; Cheeti, S.; Lu, Y.; Fahr, B.; Pham, P.; Arkin, M. R.; Walker, D. H.; Hoch, U. Bioorg. Med. Chem. Lett., 2008, doi:10.1016/j.bmcl.2008.09.073.
    • Choong, I. C.; Serafimova, I.; Fan, J.; Stockett, D.; Chan, E.; Cheeti, S.; Lu, Y.; Fahr, B.; Pham, P.; Arkin, M. R.; Walker, D. H.; Hoch, U. Bioorg. Med. Chem. Lett., 2008, doi:10.1016/j.bmcl.2008.09.073.
  • 12
    • 55549141261 scopus 로고    scopus 로고
    • note
    • 50s, the concentration required to inhibit enzyme activity by 50%, was determined for each compound under the assay conditions described.
  • 13
    • 55549103770 scopus 로고    scopus 로고
    • note
    • HCT116 cell lines were obtained from ATCC. Array Scan: HCT116 cells were treated for 16 h with serial dilutions of compound and fixed and permeabilized with 100% MeOH. The cells were then stained with either anti-RNA polymerase II serine2 (Abcam #ab5095) antibody in combination with AlexaFluor 488 anti-rabbit IgG secondary antibody (Invitrogen #A11008). The cell nuclei were stained using Hoechst 33342 (Invitrogen #3570). Fluorescence levels in the cells were then analyzed by HCS using a Cellomics ArrayScan instrument.
  • 14
    • 55549084952 scopus 로고    scopus 로고
    • note
    • 0 the initial concentration, and dQ/dt the drug flux.
  • 15
    • 55549100335 scopus 로고    scopus 로고
    • note
    • 2, 0.5 mg/mL liver microsomal protein, 1 μM test article, and 1 mM NADPH. The reaction mixture was allowed to equilibrate to 37 °C for 10 min before reactions were started by addition of NADPH. Aliquots were removed immediately, 30 min, and 60 min after addition of NADPH. Reactions were stopped by addition of acetonitrile containing internal standard (verapamil). Samples were placed on ice until centrifugation (4100g, 10 min) to remove protein content and analyzed by LC-MS/MS. Incubations with lidocaine and dextromethorphan served as positive controls and indicated that reactions functioned properly.


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.