This Letter describes the synthesis and structure-activity-relationships (SAR) of isoform-selective PLD inhibitors. By virtue of the installation of alternative halogenated piperidinyl benzimidazolone privileged structures, in combination with a key (S)-methyl group, novel PLD inhibitors with low nM potency and unprecedented levels of PLD1 isoform selectivity (approximately 1700-fold) over PLD2 were developed.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3791604 | PMC |
| http://dx.doi.org/10.1016/j.bmcl.2009.02.057 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Escitalopram reverses anxiety-like and despair behavior and affects endocannabinoid-related genes expression in the brain of adolescent male rats subjected to early life stress.
Neuroscience
January 2025
Department of Pharmacology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Medyków 18, 40-752 Katowice, Poland. Electronic address:
Due to the increasing prevalence of depressive and anxiety disorders in youth, a growing interest in the endocannabinoid system (ECS) as a potential alternative target point for treatment arised. This study aimed to investigate whether chronic administration of escitalopram reverses behavioral changes induced by maternal separation in male adolescent Wistar rats and explore the corresponding neurochemical changes in the ECS. The pups were separated from their dams for 360 min daily from postnatal day (PND) 2 until PND 15.
View Article and Find Full Text PDFChemical Probes for Investigating the Endocannabinoid System.
Curr Top Behav Neurosci
January 2025
Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Cannabis sativa has been used therapeutically since early civilizations, with key cannabinoids Δ-tetrahydrocannabinol (THC) 3.1 and cannabidiol characterized in the 1960s, leading to the discovery of cannabinoid receptors type 1 (CBR) and type 2 (CBR) and the endocannabinoid system (ECS) in the 1990s. The ECS, involving endogenous ligands like 2-arachidonoylglycerol (2-AG) 1.
View Article and Find Full Text PDFPhosphatidic acid as a cofactor of mTORC1 in platinum-based chemoresistance: Mechanisms and therapeutic potential.
Eur J Pharmacol
December 2024
Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, 14115-154, Iran. Electronic address:
Platinum-based chemotherapeutics, such as cisplatin and carboplatin, are widely used to treat various malignancies. However, the development of chemoresistance remains a significant challenge, limiting their efficacy. This review explores the multifaceted mechanisms of platinum-based chemoresistance, with a particular focus on the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, which plays a critical role in promoting tumor survival and resistance to platinum compounds.
View Article and Find Full Text PDFInhibition of phospholipase D1 reduces pancreatic carcinogenesis in mice partly through a FAK-dependent mechanism.
Carcinogenesis
November 2024
Department of Nutrition, University of California, Davis. One Shields Ave. Davis, CA, USA.
Phospholipase D (PLD) plays a critical role in cancer progression. However, its role in pancreatic cancer remains unclear. Thus, we evaluated the role of PLD1, one of two classical isoforms of PLD, in pancreatic carcinogenesis in vivo.
View Article and Find Full Text PDFDevelopment and Evaluation of Indole-Based Phospholipase D Inhibitors for Lung Cancer Immunotherapy.
J Med Chem
October 2024
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea.
This study explored novel immunomodulatory approaches for cancer treatment, with a specific focus on lung cancer, the leading cause of cancer-related deaths worldwide. We synthesized indole-based phospholipase D (PLD) inhibitors with various substituents to improve anticancer efficacy. Through structure-activity relationship studies, the key compound was identified that significantly inhibiting PLD, suppressing cell growth, viability, and migration while inducing apoptosis of lung cancer cells.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!