Three new approaches have been tested to modify existing pyridopyrimidine and alkynylpyrimidine classes of nonnucleoside adenosine kinase inhibitors 2 and 3. 4-Amino-substituted pteridines 8a-e were generally less active than corresponding 5- and 6-substituted pyridopyrimidines 2. Pyrazolopyrimidine 13c with IC(50)=7.5 nM was superior to its open chain alkynylpyrimidine analog 13g (IC(50)=22 nM) while pyrrolopyrimidines such as 17a were inactive.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.bmcl.2004.06.029 | DOI Listing |
Arch Physiol Biochem
January 2025
Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, Norway.
Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) plays a crucial role in regulation of metabolic homeostasis. To understand the role of the catalytic α2 subunit of AMPK in skeletal muscle energy metabolism, myotube cultures were established from and mice. Myotubes from mice had lower basal oleic acid and glucose oxidation compared to myotubes from mice.
View Article and Find Full Text PDFIn Silico Pharmacol
January 2025
Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, Assam 786004 India.
Unlabelled: Globally, there is an increase in the prevalence of metabolic illnesses, including diabetes mellitus. However, current therapies for diabetes and other metabolic illnesses are not well understood. Pharmacological treatment of type 2 diabetes is challenging, moreover, the majority of antidiabetic medications are incompatible with individuals who have cardiac disease, renal illness, or liver damage.
View Article and Find Full Text PDFTheranostics
January 2025
Department of Radiology, Huaxi MR Research Center (HMRRC), Institution of Radiology and Medical Imaging, Breast Center, Institute of Breast Health Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
Immunotherapy has transformed current cancer management, and it has achieved significant progress over last decades. However, an immunosuppressive tumor microenvironment (TME) diminishes the effectiveness of immunotherapy by suppressing the activity of immune cells and facilitating tumor immune-evasion. Adenosine monophosphate-activated protein kinase (AMPK), a key modulator of cellular energy metabolism and homeostasis, has gained growing attention in anti-tumor immunity.
View Article and Find Full Text PDFJ Neuroimmune Pharmacol
January 2025
Pharmacology and Toxicology Department, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
Empagliflozin (EMPA) is one of the sodium/glucose cotransporter 2 (SGLT2) inhibitors that has been recently approved for the treatment of diabetes mellitus type II. Recently, EMPA has shown protective effects in different neurological disorders, besides its antidiabetic activity. Kindling is a relevant model to study epilepsy and neuroplasticity.
View Article and Find Full Text PDFCell Rep
January 2025
Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil; Center for Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil. Electronic address:
Macrophages play a crucial role in immune responses and undergo metabolic reprogramming to fulfill their functions. The tetramerization of the glycolytic enzyme pyruvate kinase M2 (PKM2) induces the production of the anti-inflammatory cytokine interleukin (IL)-10 in vivo, but the underlying mechanism remains elusive. Here, we report that PKM2 activation with the pharmacological agent TEPP-46 increases IL-10 production in LPS-activated macrophages by metabolic reprogramming, leading to the production and release of ATP from glycolysis.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!