William F Michne

Learn More
Damnacanthal, an anthraquinone isolated from a plant extract, was found to be a potent, selective inhibitor of p56lck tyrosine kinase activity. The structure, potency, and selectivity of damnacanthal were confirmed by independent synthesis and testing. Damnacanthal exhibited an IC50 of 17 nM for inhibition of p56lck autophosphorylation and an IC50 of 620 nM(More)
Win 44,441-3 is a pure opioid antagonist in rodents in vivo and in isolated tissue preparations in vitro. Win 44,441-3 produced a weak inhibition of electrically-stimulated twitch contractions of the mouse vas deferens (MVD) and guinea-pig ileum (GPI) preparations that was not prevented by naloxone, suggesting that these effects were not mediated through(More)
The effects of tonazocine and zenazocine, two mixed agonist/antagonist analgesics, have been evaluated in a range of antinociceptive assays and in isolated tissue preparations in vitro. Both tonazocine and zenazocine were antinociceptive in writhing tests and in the i.a. bradykinin test, and were antagonists in the rat tail flick test. Additionally,(More)
In this report, we describe the discovery and characterization of a novel biarylhydrazone series of platelet-derived growth factor (PDGF) receptor tyrosine kinase inhibitors typified by the prototype WIN 41662 (3-phenyl-N1-[1-(4-pytidyl)pyrimidine]hydrazone). WIN 41662 inhibited PDGF-stimulated autophosphorylation of PDGF receptors from human vascular(More)
A homology model of the extracellular domain of the mGlu3 subtype of metabotropic glutamate (mGlu) receptor was generated and tested using site-directed mutagenesis, a radioligand-binding assay using the Group II selective agonist (2S,2'R,3'R)-2-(2',3'-[3H]dicarboxycyclopropyl) glycine ([3H]DCG-IV), and in a fluorescence-based functional assay in live(More)
Inhibition of the HIV-1 nuclear regulatory protein tat could potentially yield particularly useful drugs because it functions as an activator of transcription. It has no known cellular counterpart, and deletions in the tat gene destroy the ability of HIV-1 to replicate. We recently reported that a structurally unique class of tat inhibitors, 3-keto/enol(More)