Showing papers in "Pharmacology & Therapeutics in 1999"

TL;DR: The complex nature of EGFR biology allows for potential opportunities for EGFR inhibitors in a number of areas of cancer therapy, including proliferative, angiogenic, invasive, and metastatic aspects.

TL;DR: It has been shown that several statins decrease smooth muscle cell migration and proliferation and that sera from fluvastatin-treated patients interfere with its proliferation, and statins may have direct effects on the arterial wall, which may contribute to their antiatherosclerotic actions.

TL;DR: There now seems to be little doubt that such a process is indeed a determining factor in the extent of the lesions observed, and direct evidence for a pathogenic role for excitotoxicity in neurological disease is missing.

TL;DR: Several of the known risk factors for breast, and colon cancer may be favorably modified by dietary omega-3 FA supplementation, and the implementation of clinical chemoprevention trials is now feasible.

TL;DR: It is now generally accepted that protein phosphorylation-dephosphorylation has a role in the regulation of essentially all cellular functions as mentioned in this paper, and it is of interest that this process is involved in signal transduction.

TL;DR: Successful application of a pharmacophore model of the ATP-binding site of the epidermal growth factor receptor (EGFR) kinase led to the identification and optimization of phenylamino-pyrazolo[4,3-d]pyrimidines and substituted isoflavones and quinolones, other classes of potent, selective, and ATP competitive EGFR kinase inhibitors with IC50 values in the low nanomolar range.

TL;DR: X-ray crystallographic analysis of p38-inhibitor complexes reinforces the observations made from site-directed mutagenesis studies, thereby providing a molecular basis for understanding the kinase selectivity of these inhibitors.

TL;DR: This review is a survey of various approaches to targeting cytotoxic anticancer drugs to tumors primarily through biomolecules expressed by cancer cells or associated vasculature and stroma and focuses on a mechanistic understanding of selective drug release or generation at the tumor site.

TL;DR: It is demonstrated that the identification of PTKs that play a key role in a defined disease state can lead to a selective drug.

TL;DR: It appears that the significant progress that is being made in the molecular understanding of DA receptors will continue to have a tremendous impact in the pharmacological treatment of neuropsychiatric, cardiovascular, and renal diseases.

TL;DR: In this paper, both cationic and neutral synthetic ligands that bind in the minor groove of DNA are discussed, and both bis-distamycins and related lexitropsins show activities against human immunodeficiency virus (HIV)-1 and HIV-2 at low nanomolar concentrations.

TL;DR: The structural aspects of the interactions of several anticancer drugs acting on the backbone of B-DNA double-helix are reviewed, finding that specific atomic sites on DNA are often the targets for drug covalent actions.

TL;DR: Findings suggest that compounds targeting specific neuropeptide receptors may become an alternative to benzodiazepines for the treatment of anxiety disorders.

TL;DR: The combined use of combinatorial chemistry--to generate large numbers of structurally diverse compounds--and of high throughput screening systems--to speed up the testing of compounds--hopefully will help to optimize the process.

TL;DR: The strengths and limitations of heterologously expressed enzymes as they affect in vitro drug metabolism studies are discussed and emphasis is given to new applications that have been enabled by high level, functional expression of CYP enzymes.

TL;DR: The justification for targeting the EGFR family for cancer therapeutics is addressed, some of the more promising kinase inhibitors that are in development are highlighted, and new structural classes have emerged that exhibit enormous improvements with regard to potency, specificity, and in vitro and in vivo activity.

TL;DR: In this paper, the key techniques currently available are reviewed and the advantages, disadvantages, and potential artifacts of each are discussed.

TL;DR: The focus of this review is to compare the similarities and differences among the three alpha2AR subtypes in terms of specificity, signaling, and trafficking, and it is anticipated that a molecular understanding of receptor trafficking will lead to novel therapeutic strategies for diseases linked to aberrant adrenergic receptor function or localization.

TL;DR: The authors' understanding of fetal hepatic elimination processes has advanced steadily over the years, but future developments, however, should consider more fully the influence of the unique physiological milieu of the fetal liver, in addition to the expression and activity of drug metabolizing enzymes.

TL;DR: To address the need for additional chemotypes that may serve as lead structures for drugs that would not have the toxicities associated with flavopiridol, compounds with a similar pattern of cell growth inhibitory activity in the National Cancer Institute's in vitro anticancer drug screen have been recognized and screened for anti-CDK activity in a biochemical screen.

TL;DR: CGP 41251 showed in vivo antitumor activity as single agent and inhibited angiogenesis in vivo, and is able to reverse the p-glycoprotein-mediated multidrug resistance of tumor cells in vitro, showing broad antiproliferative activity against various tumor and normal cell lines in vitro.

TL;DR: In this review, recent advances in computational methods for database searching and docking, de novo drug design, and estimation of ligand binding affinities are discussed.

TL;DR: Stimulation of PKB activity protects cells from apoptosis by phosphorylation and inactivation of the pro-apoptotic protein BAD, which could explain why PKB is overexpressed in some ovarian, breast, and pancreatic carcinomas.

TL;DR: A recent review as discussed by the authors summarizes current progress in this field under the following general topics: (1) the wide distribution of acid RNases in organisms from viruses to animals; (2) recent findings concerning their primary and three-dimensional structure; (3) the structure-function relationship of acidRNases, with a fungal RNase from Rhizopus niveus as a model enzyme; (4) the unique localization of acid RBs in the periplasm of bacteria, vacuoles in plants, and lysosomes of animals and protozoa;

TL;DR: A brief survey of the extensive literature on metabolism of delta 9-tetrahydrocannabinol to the acids is presented, while more emphasis is given to the recent findings on the biological actions of this class of CBs.

TL;DR: A considerable number of iron(III) chelators, designed for purposes other than treating malaria, have antimalarial activity in vitro, apparently through the mechanism of withholding iron from vital metabolic pathways of the intra-erythrocytic parasite.

TL;DR: A unique vasodilator is found that preferentially suppresses delayed cerebral vasospasm, a critical complication of subarachnoid hemorrhage, without significant changes in systemic blood pressure.

TL;DR: In this article, a defense mechanism that is able to distinguish microbial DNA from our own because of differences in the frequency and methylation of CpG dinucleotides in particular base contexts is described.

TL;DR: Preclinical and clinical studies have shown that COMT inhibitors markedly enhance levodopa availability and prolong its plasma half-life, and COMT inhibition promises to become an important means of extending the benefits oflevodopa therapy in PD.

TL;DR: The conclusion notes the concentration of studies on the classical transmitters, with relative neglect of the effects of ethanol on peptides and on neuronal interactions between brain areas and integrated patterns of neuronal activity.