Synthesis of a novel class of cdc25A inhibitors from Vitamin D3

Bioorganic and Medicinal Chemistry Letters

Volumn 10, Issue 7, 2000, Pages 615-617

  Dodo, Kosuke ^a   Takahashi, Masato ^a   Yamada, Yuji ^b   Sugimoto, Yoshikazu ^b   Hashimoto, Yuichi ^a   Shirai, Ryuichi ^c  

^a UNIVERSITY OF TOKYO   (Japan)

^b TAIHO PHARMACEUTICAL CO LTD   (Japan)

^c NARA INSTITUTE OF SCIENCE AND TECHNOLOGY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

COLECALCIFEROL; DYSIDIOLIDE; PHOSPHOPROTEIN PHOSPHATASE; PHOSPHOPROTEIN PHOSPHATASE INHIBITOR;

ANTINEOPLASTIC ACTIVITY; ARTICLE; BLOCKING FACTOR; CELL CYCLE; CELL STRAIN HL 60; CHEMICAL MODIFICATION; DRUG DESIGN; DRUG INHIBITION; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; HUMAN CELL; STRUCTURE ANALYSIS;

4-BUTYROLACTONE; ANTINEOPLASTIC AGENTS; CDC25 PHOSPHATASE; CHOLECALCIFEROL; ENZYME INHIBITORS; G1 PHASE; HL-60 CELLS; HUMANS;

EID: 0034599466     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(00)00065-2     Document Type: Article

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11. 3) data are as follows: 3a (clear oil): δ 5.47 (1H, s), 3.82-3.87 (1H, m), 3.69 (3H, s), 2.10 (1H, t, J = 8 Hz), 2.02 (1H, br d, J = 6 Hz), 0.93 (3H, d, J = 6 Hz), 0.87 (3H, d, J = 7 Hz), 0.86 (3H, d, J = 7 Hz), 0.57 (3H, s). 3b (colorless crystals, mp. 117-118°C): δ 5.50 (1H, s), 3.81-3.87 (1H, m), 2.13 (1H, t, J = 7 Hz), 2.03 (1H, br d, J = 6 Hz), 0.93 (3H, d, J = 6 Hz), 0.87 (3H, d, J = 7 Hz), 0.86 (3H, d, J = 7 Hz), 0.59 (3H, s).
12. cdc25A phosphatase assay: catalytic domain protein of human cdc25A (283-523 aa) was produced from Escherichia coli strain DH5α using pGEX-2T glutathione-S-transferase (GST)-fusion protein expression vector (Pharmacia) according to the instructions provided by the manufacturer. Phosphatase activity of cdc25A was assayed in 100 μL of buffer containing 10 mM HEPES (pH 8.0), 50 mM NaCl, and 1 mM dithiothreitol (DTT), with 10 mM p-nitrophenol phosphate (Sigma) as a substrate, using 96-well microtiter plates.
13. 50 value was defined as the drug concentration needed to cause 50% inhibition of cell growth with respect to the control.
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