Abstract:
:The synthesis and biochemical characterization of AX4697, a fluorescent, bisindolylmaleimide-derived probe for PKCalpha and beta, is described. AX4697 was able to quantify changes in PKC expression in drug-treated Jurkat cells and was shown to covalently label PKCalpha on C619, a residue that sits just outside the active site.
journal_name
Bioorg Med Chem Lettjournal_title
Bioorganic & medicinal chemistry lettersauthors
Liu Y,Wu J,Weissig H,Betancort JM,Gai WZ,Leventhal PS,Patricelli MP,Samii B,Szardenings AK,Shreder KR,Kozarich JWdoi
10.1016/j.bmcl.2008.08.045subject
Has Abstractpub_date
2008-11-15 00:00:00pages
5955-8issue
22eissn
0960-894Xissn
1464-3405pii
S0960-894X(08)00964-5journal_volume
18pub_type
杂志文章abstract::A series of novel pyrimido[1,2-b]indazoles 5, 7 have been prepared from 3-trifluoromethyl-5-phenyl-2,6-dicyano anilines 1 via novel indazole regioisomers 3 and 4 through a facile strategy. Specific examples were evaluated for anticancer activity in vitro and found to exhibit promising activity against A-549 cell lines...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2007.03.087
更新日期:2007-06-15 00:00:00
abstract::DNA is a promising functional molecule to modify and design lipid membrane functions. In order to use DNA in a hydrophilic-hydrophobic interface including lipid membrane, we have developed an amphiphilic DNA having dodecyl phosphotriester linkages (dod-DNA). Herein, we report the binding of a series of amphiphilic dod...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
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journal_title:Bioorganic & medicinal chemistry letters
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doi:10.1016/s0960-894x(00)00551-5
更新日期:2000-12-18 00:00:00
abstract::The synthesis and evaluation of small molecule antagonists of the G protein-coupled receptor NPBWR1 (GPR7) are reported for the first time. [4-(5-Chloropyridin-2-yl)piperazin-1-yl][(1S,2S,4R)-4-{[(1R)-1-(4-methoxyphenyl)ethyl]amino}-2-(thiophen-3-yl)cyclohexyl]methanone (1) emerged as a hit from a high-throughput scre...
journal_title:Bioorganic & medicinal chemistry letters
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abstract::A set of 15mer linear oligoDNA probes bearing a modified nucleoside conjugated with a polyamine/fluorescein/anthraquinone reporting moiety were synthesized. In a single-stranded form, the fluorescence generated by the excitation of fluorescein was efficiently quenched, while marked recovery of the fluorescence was obs...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2006.02.016
更新日期:2006-05-15 00:00:00
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journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
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更新日期:2001-05-07 00:00:00
abstract::2-aminoethylbenzofurans constitute a new class of H(3) antagonists that are more rotationally constrained than most previously reported H(3) antagonists. They retain high potency at human and rat receptors, with efficient CNS penetration observed in 35. The SAR of the basic amine moiety was compared in three different...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2003.11.032
更新日期:2004-02-09 00:00:00
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journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2004.03.040
更新日期:2004-06-07 00:00:00
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journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
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journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
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更新日期:1999-09-06 00:00:00
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journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2011.03.107
更新日期:2011-05-15 00:00:00
abstract::Pulvinone and several 3-fluoro-4-morpholino substituted pulvinone derivatives were synthesized in five steps from a common precursor, phenyl acetic acid. Most of synthetic morpholine substituted pulvinones showed inhibitory activity against Esherichia coli. For the first time, the inhibition of pulvinone and its deriv...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2012.11.090
更新日期:2013-02-01 00:00:00
abstract::A fluorescent sensor based on a tripeptide (SerGluGlu) with a dansyl fluorophore detected selectively Al(III) among 16 metal ions in aqueous buffered solutions without any organic cosolvent. The peptide-based sensor showed a highly sensitive turn on response to aluminium ion with high binding affinity (1.84×10(4)M(-1)...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2016.07.073
更新日期:2016-09-15 00:00:00
abstract::Structure-activity relationship studies directed toward improving the metabolic stability of compound 1 resulted in the identification of 3-[5-(3,5-difluorophenyl)-3-({[(1S,3R)-3-fluorocyclopentyl]amino}methyl)-4-methyl-1H-pyrazol-1-yl]propanenitrile 39 (MK-1925) as a selective, orally available and brain-penetrable o...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2009.06.051
更新日期:2009-08-15 00:00:00
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journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2013.10.067
更新日期:2013-12-15 00:00:00
abstract::Steroidal glucocorticoids (GR agonists) have been widely used for the topical treatment of skin disorders, including atopic dermatitis. They are a very effective therapy, but they are associated with both unwanted local effects in the skin (skin thinning/atrophy) and systemic side effects. These effects can limit the ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2020.127402
更新日期:2020-09-01 00:00:00
abstract::The first non-substrate like inhibitors of human cytosolic phosphoenolpyruvate carboxykinase (PEPCK) competitive with GTP are reported. An effort to discover orally active compounds that improve glucose homeostasis in Type 2 diabetics by reversibly inhibiting PEPCK led to the discovery of 1-allyl-3-butyl-8-methylxanth...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
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journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2007.01.039
更新日期:2007-04-01 00:00:00
abstract::Quantitative fluorescence-based methods have been developed to determine the nuclear concentration of polyamide-fluorescein conjugates in cell culture. Confocal laser scanning microscopy and flow cytometry techniques are utilized to plot calibration curves, from which the nuclear concentration can be interpolated. Upo...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2008.05.063
更新日期:2008-11-15 00:00:00
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journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2011.06.078
更新日期:2011-09-15 00:00:00
abstract::The synthesis and evaluation of new analogues of thieno[2,3-d]pyrimidin-4-yl hydrazones are described. 2-Pyrdinecarboxaldehyde [6-(tert-butyl)thieno[2,3-d]pyrimidine-4-yl]hydrazone derivatives have been identified as cyclin-dependent kinase 4 (CDK4) inhibitors. The potency, selectivity profile, and structure-activity ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2008.11.090
更新日期:2009-01-15 00:00:00
abstract::Proteases typically recognize their peptide substrates in extended conformations. General approaches for designing protease inhibitors often consist of peptidomimetics that feature this conformation. Herein we discuss a combination of computational and experimental studies to evaluate the potential of triazole-linked ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2009.09.049
更新日期:2009-11-01 00:00:00
abstract::Drug design efforts in the emerging 2-aminothiazole-4-carboxamide class of CHK1 inhibitors have uncovered specific combinations of key substructures within the molecule; resulting in significant improvements in cell-based activity while retaining a greater than one hundred-fold selectivity against CDK2. The X-ray crys...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2013.02.108
更新日期:2013-05-01 00:00:00
abstract::We have synthesized a novel vitamin D receptor agonist VS-105 ((1R,3R)-5-((E)-2-((3αS,7αS)-1-((R)-1-((S)-3-hydroxy-2,3-dimethylbutoxy)ethyl)-7α-methyldihydro-1H-inden-4(2H,5H,6H,7H,7αH)-ylidene)ethylidene)-2-methylenecyclohexane-1,3-diol). Preparation of a-ring phenylphosphine oxide 11, followed by Wittig-Horner coupl...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2013.08.076
更新日期:2013-11-01 00:00:00
abstract::Isoxazoles are frequently used amide isosteres, as shown in the context of discovery of CRTh2 antagonists from amide 1 to isoxazole 2. However, persistent agonism and poor solubility in isoxazole series presented challenges to its further development. Based on the concept of quality by design (QbD), 5,5-disubstituted ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2014.01.043
更新日期:2014-03-15 00:00:00
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journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
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更新日期:2020-10-01 00:00:00
abstract::Mammalian target of rapamycin (mTOR) is a promising target for the development of anticancer medicines. Here, we report the first example for a successful application of the structure-based virtual screening to identify new mTOR inhibitors. Using the scoring function improved by implementing the ligand solvation effec...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2013.12.081
更新日期:2014-02-01 00:00:00
abstract::A novel series of indole/indazole-aminopyrimidines was designed and synthesized with an aim to achieve optimal potency and selectivity for the c-Jun kinase family or JNKs. Structure guided design was used to optimize the series resulting in a significant potency improvement. The best compound (17) has IC50 of 3 nM for...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 信件
doi:10.1016/j.bmcl.2013.04.029
更新日期:2013-06-15 00:00:00
abstract::In this study, we synthesized a series of enantiomerically pure (2R,3S)-disubstituted tetrahydropyranes with diverse functional groups using known methodologies. In addition to the tert-butyl dimethyl silyl group, other common protecting groups for hydroxyl groups such as allyl, acetate, and benzoate were used to obta...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2005.05.126
更新日期:2005-08-01 00:00:00
abstract::The eryA gene of the bacterial pathogen Brucella abortus has been functionally expressed in Escherichia coli. The resultant EryA was shown to catalyze the ATP-dependent conversion of erythritol to L-erythritol-4-phosphate (L-E4P). The steady state kinetic parameters of this reaction were determined and the enzyme was ...
journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(02)01032-6
更新日期:2003-02-24 00:00:00