AI Article Synopsis
- The study focuses on creating glutamic acid analogs that selectively favor one diastereomer for use with metabotropic glutamate receptor subtype 4 (mGluR4).
- These analogs are designed using a cyclopropane structure that has a fluorine atom and an α-amino acid group.
- One specific analog, racemic analog 11a, showed promising results as an agonist with a concentration required for half-maximal effectiveness (EC50) of 340 nM, indicating its potential as a drug candidate.
Article Abstract
Herein we describe the diastereoselective synthesis of glutamic acid analogs and the evaluation of their agonist activity towards metabotropic glutamate receptor subtype 4 (mGluR4). These analogs are based on a monofluorinated cyclopropane core substituted with an α-aminoacid function. The potential of this new building block as a tool for the development of a novel class of drugs is demonstrated with racemic analog 11a that displayed the best agonist activity with an EC50 of 340 nM.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmc.2012.06.006 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
New PPARα Agonist A190-Loaded Microemulsion for Chemotherapy-Induced Peripheral Neuropathy.
Mol Pharm
January 2025
Department of Pharmaceutics, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia 23298, United States.
Chemotherapy-induced peripheral neuropathy (CIPN) is a serious side effect of anticancer agents with limited effective preventive or therapeutic interventions. Although fenofibrate, a peroxisome proliferator-activated receptor-alpha (PPARα) agonist, has demonstrated neuroprotective and analgesic properties, its clinical utility is hindered by low receptor affinity, poor subtype selectivity, and suboptimal bioavailability. A190, a highly selective and potent nonfibrate PPARα agonist, offers a promising alternative but is limited by poor aqueous solubility, resulting in reduced oral bioavailability and therapeutic efficacy.
View Article and Find Full Text PDFMetabolically stable apelin analogs: development and functional role in water balance and cardiovascular function.
Clin Sci (Lond)
January 2025
Center for Interdisciplinary Research in Biology, College de France, Institut National de la Santé et de la Recherche Médicale, Paris, France.
Apelin, a (neuro) vasoactive peptide, plays a prominent role in controlling water balance and cardiovascular functions. Apelin and its receptor co-localize with vasopressin in magnocellular vasopressinergic neurons. Apelin receptors (Apelin-Rs) are also expressed in the collecting ducts of the kidney, where vasopressin type 2 receptors are also present.
View Article and Find Full Text PDFLongitudinal Analysis of Obesity Drug Use and Public Awareness.
JAMA Netw Open
January 2025
Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Importance: Obesity, a chronic disease with escalating global prevalence, poses considerable health risks. Glucagon-like peptide 1 receptor agonists (GLP-1RAs), including liraglutide, semaglutide, and tirzepatide, have demonstrated efficacy for weight loss in clinical trials. The paradigm shift in the approach to obesity management drugs (OMDs) may offer an opportunity to examine online search activity and prescription trends.
View Article and Find Full Text PDFFoxO1 promotes high glucose-induced inflammation and cataract formation via JAK1/STAT1.
Graefes Arch Clin Exp Ophthalmol
January 2025
National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, 270 Xueyuan West Road, Wenzhou, 325027, Zhejiang, China.
Purpose: To investigate whether in diabetic cataract (DC), FoxO1 regulates high glucose (HG)-induced activation of NLRC4/IL-6 inflammatory mediators in human lens epithelial cells (SRA01/04) via the JAK1/STAT1 pathway, leading to cataract formation.
Methods: Expression levels of FoxO1, inflammatory factor IL-6 and inflammatory vesicle NLRC4 were examined in SRA01/04 under high glucose (HG) stress at 25-150 mM. Rat lenses were also cultured using HG medium with or without the addition of the FoxO1 inhibitor AS1842856 and the JAK1 agonist RO8191.
Intralesional injection of CpG ODNs complexed with glatiramer acetate mitigates systemic cytokine toxicities and synergistically advances checkpoint blockade efficacy.
Drug Deliv Transl Res
January 2025
Kinimmune, Inc. St. Louis, 63141, Missouri, USA.
PD-L1/PD-1 checkpoint inhibitors (CPIs) are mainstream agents for cancer immunotherapy, but the prognosis is unsatisfactory in solid tumor patients lacking preexisting T-cell reactivity. Adjunct therapy strategies including the intratumoral administration of immunostimulants aim to address this limitation. CpG oligodeoxynucleotides (ODNs), TLR9 agonists that can potentiate adaptive immunity, have been widely investigated to tackle PD-L1/PD-1 resistance, but clinical success has been hindered by inconsistent efficacy and immune-related toxicities caused by systemic exposure.
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!