Effect of novel N-cyano-tetrahydro-pyridazine compounds, a class of cathepsin K inhibitors, on the bone resorptive activity of mature osteoclasts

Bioorganic and Medicinal Chemistry Letters

Volumn 18, Issue 14, 2008, Pages 3988-3991

  Kim, Seong Hwan ^a   Jhon, Dong Joo ^a   Song, Jong Hwan ^a   No, Jae Sung ^a   Kang, Nam Sook ^a  

^a Korea Research Institute of Chemical Technology   (South Korea)

Author keywords

Bone resorption; Cathepsin K; Docking; Inhibitor; Osteoclast

Indexed keywords

[1 (2 CYANOTETRAHYDROPYRIDAZINE 1 CARBONYL) 2 METHYLPROPYL]CARBAMIC ACID BENZYL ESTER; CATHEPSIN K; CATHEPSIN K INHIBITOR; CYANIDE; N CYANOTETRAHYDROPYRIDAZINE DERIVATIVE;

ANIMAL CELL; ARTICLE; COMPUTER PROGRAM; CONTROLLED STUDY; CORRELATION ANALYSIS; DRUG EFFECT; DRUG SYNTHESIS; ENZYME ACTIVITY; ENZYME BINDING; ENZYME INHIBITION; IC 50; MOLECULAR DOCKING; MOUSE; NONHUMAN; OSTEOCLAST; OSTEOLYSIS; PREDICTION; SCORING SYSTEM;

ANIMALS; BINDING SITES; BONE AND BONES; BONE RESORPTION; CATHEPSINS; CHEMISTRY, PHARMACEUTICAL; DRUG DESIGN; HUMANS; INHIBITORY CONCENTRATION 50; LIGANDS; MICE; MODELS, CHEMICAL; OSTEOBLASTS; OSTEOCLASTS; PYRIDAZINES;

EID: 47149107203     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2008.06.017     Document Type: Article

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11. 3 cells/well. The medium was replaced with a fresh one every 3 days. Multinucleated osteoclasts were observed from the differentiation day 3, and at that time, compound 8 was treated into multinucleated osteoclasts derived from RAW264.7 cells. After the incubation for 3 days, the slides were washed with 6% sodium hypochloride solution to remove cells. The resorbed areas on the slides were observed under a microscope. M-CSF-dependent BMMs were plated and cultured in αMEM with 10% FBS, 100 ng/ml RANKL, and 30 ng/ml M-CSF. The medium was replaced with a fresh one every 3 days. Multinucleated osteoclasts were observed on the differentiation day 6, and at that time, compound 8 was added every 3 days. On the differentiation day 15, the slides were washed and observed as described above. This experiment was performed in triplicate. Quantification of resorbed area was performed by using Image Pro-plus program, version 4.0 (Media Cybernetics Inc., MD).