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Estrogen receptor-beta potency-selective ligands: structure-activity relationship studies of diarylpropionitriles and their acetylene and polar analogues.
TLDR
This study suggests that, in this series of ligands, the nitrile functionality is critical to ERbeta selectivity because it provides the optimal combination of linear geometry and polarity. Expand
Structural characterization of a subtype-selective ligand reveals a novel mode of estrogen receptor antagonism
TLDR
Crystal structures of the ERα ligand binding domain (LBD) bound to both THC and a fragment of the transcriptional coactivator GRIP1, and the ERβ LBD bound to THC are determined and it is revealed that THC does not act on ERβ through the same mechanisms used by other known ER antagonists. Expand
A Benzothiophene Inhibitor of Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 Inhibits Tumor Necrosis Factor α Production and Has Oral Anti-Inflammatory Efficacy in Acute and Chronic
TLDR
PF-3644022 is a potent freely reversible ATP-competitive compound that inhibits MK2 activity with good selectivity when profiled against 200 human kinases and displays good pharmacokinetic parameters in rats and is orally efficacious in both the rat acute LPS-induced TNFα model and the chronic streptococcal cell wall-induced arthritis model. Expand
Pyrrolopyridine inhibitors of mitogen-activated protein kinase-activated protein kinase 2 (MK-2).
TLDR
A new class of potent kinase inhibitors selective for mitogen-activated protein kinase-activatedprotein kinase 2 (MAPKAP-K2 or MK-2) for the treatment of rheumatoid arthritis has been prepared and evaluated and their activity in both in vitro and in vivo models is discussed. Expand
Novel Ligands that Function as Selective Estrogens or Antiestrogens for Estrogen Receptor-α or Estrogen Receptor-β.
TLDR
These compounds should be useful in probing the conformational changes in these two ERs that are evoked by agonists and antagonists, and in evaluating the distinct roles that ER beta and ER alpha may play in the diverse target tissues in which estrogens act. Expand
Novel ligands that function as selective estrogens or antiestrogens for estrogen receptor-alpha or estrogen receptor-beta.
TLDR
These compounds should be useful in probing the conformational changes in these two ERs that are evoked by agonists and antagonists, and in evaluating the distinct roles that ER beta and ER alpha may play in the diverse target tissues in which estrogens act. Expand
Benzothiophene inhibitors of MK2. Part 1: structure-activity relationships, assessments of selectivity and cellular potency.
TLDR
Crystallographic data provide a rationale for the observed MK2 potency as well as selectivity over CDK2 for this class of inhibitors. Expand
Estrogen receptor subtype-selective ligands: asymmetric synthesis and biological evaluation of cis- and trans-5,11-dialkyl- 5,6,11, 12-tetrahydrochrysenes.
TLDR
This study illustrates that the antagonist character in THC ligands for ERbeta depends in a progressive way on the size and geometric disposition of substituent groups and suggests that the induction of an antagonist conformation in ERbeta can be achieved with these ligands with less steric perturbation than in ERalpha. Expand
Plasmepsins IX and X are essential and druggable mediators of malaria parasite egress and invasion
TLDR
It is shown that PMIX is essential for erythrocyte invasion, acting on rhoptry secretory organelle biogenesis, and PMX isessential for both egress and invasion, controlling maturation of the subtilisin-like serine protease SUB1 in exoneme secretory vesicles. Expand
Benzothiophene inhibitors of MK2. Part 2: improvements in kinase selectivity and cell potency.
Optimization of kinase selectivity for a set of benzothiophene MK2 inhibitors provided analogs with potencies of less than 500 nM in a cell based assay. The selectivity of the inhibitors can beExpand
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