Imidazo[4,5-d]thiazolo[5,4-b]pyridine based inhibitors of IKK2: Synthesis, SAR, PK/PD and activity in a preclinical model of rheumatoid arthritis

Bioorganic and Medicinal Chemistry Letters

Volumn 21, Issue 1, 2011, Pages 383-386

  Dyckman, Alaric J ^a   Langevine, Charles M ^a   Quesnelle, Claude ^a   Kempson, James ^a   Guo, Junqing ^a   Gill, Patrice ^a   Spergel, Steven H ^a   Watterson, Scott H ^a   Li, Tianle ^a   Nirschl, David S ^a   Gillooly, Kathleen M ^a   Pattoli, Mark A ^a   McIntyre, Kim W ^a   Chen, Laishun ^a   McKinnon, Murray ^a   Dodd, John H ^a   Barrish, Joel C ^a   Burke, James R ^a   Pitts, William J ^a  

^a BRISTOL MYERS SQUIBB   (United States)

Author keywords

IKK; IKK ; IKK2; NF B

Indexed keywords

I KAPPA B KINASE INHIBITOR; IMIDAZO[4,5 D]THIAZOLO[5,4 B]PYRIDINE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DRUG ACTIVITY; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENCY; DRUG SYNTHESIS; FEMALE; MALE; MOUSE; NONHUMAN; RHEUMATOID ARTHRITIS; STRUCTURE ACTIVITY RELATION;

ANIMALS; ARTHRITIS, RHEUMATOID; DISEASE MODELS, ANIMAL; DOGS; DRUG EVALUATION, PRECLINICAL; FEMALE; I-KAPPA B KINASE; IMIDAZOLES; MICE; MICE, INBRED BALB C; PROTEIN KINASE INHIBITORS; PYRIDINES; RATS; STRUCTURE-ACTIVITY RELATIONSHIP; THIAZOLES;

MURINAE;

EID: 78650516923     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.10.133     Document Type: Article

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17. 2, 34 mM sodium phosphate, 3 mM NaCl, 0.6 mM potassium phosphate, 1 mM KCl, 1 mM dithiothreitol, 5% (w/v) glycerol, and 470 μg/mL bovine serum albumin. After 60 min, the kinase reactions were stopped by the addition of EDTA to 33 mM. IκBα phosphorylation was quantitated by competition for binding to an anti-phospho-IκBα antibody (SantaCruz Biotechnology #sc-8404) with fluorescein-labeled phospho-peptide ([FL]-Asp-Asp-Arg-His-Asp-[p]Ser-Gly-Leu- Asp-Ser-Met-Lys-NH2) as measured using fluorescence polarization.
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