Neuroscience Research, Global Pharmaceutical Research, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA.
Published: June 2005
AI Article Synopsis
Article Abstract
4-Amino-5,7-disubstituted pyridopyrimidines are potent, non-nucleoside inhibitors of adenosine kinase (AK). We recently identified a potent, orally efficacious analog, 4 containing a 7-pyridylmorpholine substituted ring system as the key structural element of this template. In this report, we disclose the pharmacologic effects of five- and six-membered heterocyclic ring replacements for the pyridine ring in 4. These replacements were found to have interesting effects on in vivo efficacy and genotoxicity as well as in vitro potency. We discovered that the nitrogen in the heterocyclic ring at C(7) is important for the modulation of mutagenic side effects (Ames assay).
Shanghai Key Laboratory for Veterinary and Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, 200240, China. Electronic address:
Epigallocatechin gallate (EGCG), a natural antioxidant, plays a vital role in modulating sperm function, yet its protective impact on boar spermatozoa during liquid preservation at 4 °C remains elusive. This study aimed to investigate the beneficial effects of EGCG on boar semen preservation, and elucidate the potential mechanism. Multiple parameters including sperm quality, anti-oxidative status, protein phosphorylation levels, membrane receptor and cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) signaling pathways were analyzed using computer-assisted semen analysis system, Western blot and molecular docking techniques.
The phosphorylation reaction, catalyzed by the enzyme protein kinase A (PKA), plays one of the key roles in the work of the glutamatergic system, primarily involved in memory functioning. The analysis of the dynamic behavior of the enzyme-substrate complex allows one to learn the mechanism of the enzymatic reaction. According to the results of classical molecular dynamics calculations followed by hierarchical clustering, the most preferred proton acceptor during the phosphorylation reaction catalyzed by PKA is the carboxyl group of the amino acid residue Asp166; however, the γ-phosphate group of ATP can also act as an acceptor.
Background: The aging of skin is a diversified biological phenomenon, influenced by a combination of genetic and environmental factors. However, the specific mechanism of skin photoaging is not yet completely elucidated.
Methods: Gene expression profiles for photoaging patients were obtained from the Gene Expression Omnibus (GEO) collection.
Activation of PLCβ enzymes by G and G proteins is a common mechanism to trigger cytosolic Ca increase. We and others reported that G inhibitor FR900358 (FR) can inhibit both and G - and, surprisingly, G -mediated intracellular Ca mobilization. Thus, the G -G -PLCβ-Ca signaling axis depends entirely on the presence of active G , which reasonably explained FR-inhibited G -induced Ca release.
Immune checkpoint inhibitors, especially those targeting CD274/PD-L1yield powerful clinical therapeutic efficacy. Thoughmuch progress has been made in the development of antibody-basedCD274 drugs, chemical compounds applied for CD274degradation remain largely unavailable. Herein,baicalein, a monomer of traditional Chinese medicine, isscreened and validated to target CD274 and induces itsmacroautophagic/autophagic degradation.
