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Potent EGFR/PARP-1 inhibition by spirooxindole-triazole hybrids for targeted liver cancer therapy.
RSC Adv
January 2025
Department of Chemistry, College of Science, King Saud University P. O. Box 2455 Riyadh 11451 Saudi Arabia
The search for effective anti-cancer therapies has led to the exploration of dual inhibition strategies targeting multiple key molecular pathways. In this study, we aimed to design a novel candidate capable of dual inhibition targeting both EGFR (Epidermal Growth Factor Receptor) and PARP-1 (poly(ADP-ribose)polymerase-1), two crucial proteins implicated in cancer progression and resistance mechanisms. Through molecular hybridization and structure-based drug design approaches, we synthesized a series of compounds based on spirooxindole with triazole scaffolds with the potential for dual EGFR and PARP-1 inhibition.
View Article and Find Full Text PDFMulti Targeted Activity of Cocculus hirsutus through Modulation of DPP-IV and PTP-1B Leading to Enhancement of Glucose Uptake and Attenuation of Lipid Accumulation.
Appl Biochem Biotechnol
January 2025
Tissue Culture and Drug Discovery Laboratory, Department of Biotechnology, Anna University, Chennai, 600 025, India.
Article Synopsis
- Multi-targeted therapies are increasingly recognized for their effectiveness in treating complex diseases such as Type 2 diabetes and obesity, utilizing multiple mechanisms to enhance benefits while minimizing side effects.
- The study investigates the potential of Cocculus hirsutus methanol extract (CME) and its hydromethanolic fraction (HMF), revealing significant inhibition of key enzymes related to glucose metabolism and insulin signaling, which indicates their potential in improving metabolic health.
- HMF was particularly effective, showing improved glucose uptake, increased insulin sensitivity through GLUT4 expression, and reduced lipid accumulation by inhibiting adipogenesis regulators, marking its promise as a therapeutic option.
Efficacy and safety of multi-target tyrosine kinase inhibitor AL2846 combined with gemcitabine in pancreatic cancer.
Invest New Drugs
January 2025
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
Pancreatic cancer patients urgently need new treatments, and we explored the efficacy and safety of combination therapy with AL2846 and gemcitabine in pancreatic cancer patients. This was a single-arm, single-center, open-label phase I/IIa study (NCT06278493). The dose-escalation phase was designed to evaluate the maximum tolerated dose (MTD) of AL2846 combined with gemcitabine.
View Article and Find Full Text PDFExploration of novel triazolo-thiadiazine hybrids of deferasirox as multi-target-directed anti-neuroinflammatory agents with structure-activity relationship (SAR): a new treatment opportunity for Alzheimer's disease.
RSC Adv
January 2025
Department of Chemistry, COMSATS University Islamabad, Abbottabad Campus 22060 Pakistan +92334517999 +923005316570.
It is believed that inflammation influences several physiological processes, including the function of the central nervous system. Moreover, the impairment of lipid mechanisms/pathways is associated with neurodegenerative disorders and onset of Alzheimer's disease (AD). AD is a chronic neurodegenerative disease representing the major cause of dementia worldwide.
View Article and Find Full Text PDFBefA protein alleviates progression of non-alcoholic fatty liver disease by modulating the AMPK signaling pathway through the gut-liver axis.
Int J Biol Macromol
January 2025
School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, China; Department National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, Nanchang, China. Electronic address:
Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver diseases worldwide, necessitating urgent novel oral treatments. In this study, β-cell expansion factor A (BefA) was evaluated in a murine NAFLD model induced by high-fat diet (HFD). Our results revealed that BefA significantly reduced body weight (36.
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