AI Article Synopsis
- The research focused on finding a new type of TRPV1 antagonist, which could be used in treating various medical conditions.
- The chemical structure of an existing compound (hit compound 7) was modified, leading to an improved version (15d) that showed significantly stronger inhibitory activity against human TRPV1.
- The modified compound 15d also successfully reduced bladder overactivity in rats during in vivo testing.
Article Abstract
We aimed to discover a novel type of transient receptor potential vanilloid 1 (TRPV1) antagonist because such antagonists are possible drug candidates for treating various disorders. We modified the structure of hit compound 7 (human TRPV1 IC50=411 nM) and converted its pyrrolidino group to a (hydroxyethyl)methylamino group, which substantially improved inhibitory activity (15d; human TRPV1 IC50=33 nM). In addition, 15d ameliorated bladder overactivity in rats in vivo.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmcl.2013.04.016 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Genistein-3'-sodium sulfonate suppresses NLRP3-mediated cell pyroptosis after cerebral ischemia.
Metab Brain Dis
January 2025
Key Laboratory of Prevention and treatment of cardiovascular and cerebrovascular diseases of Ministry of Education, Gannan Medical University, Ganzhou, 341000, China.
Cerebral ischemia-induced pyroptosis contributes to the dissemination of neuroinflammation, and Nod-like receptor protein-3 (NLRP3) inflammasome plays a key role in this process. Previous studies have indicated that Genistein-3'-sodiumsulfonate (GSS) can inhibit neuroinflammation caused by cerebral ischemia, exert cerebroprotective effects, but its specific mechanism has not been comprehensively understood. The aim of this study was to explore the effect of GSS on ischemic stroke-induced cell pyroptosis.
View Article and Find Full Text PDFNatural phenylethanoid glycoside forsythoside A alleviates androgenetic alopecia by selectively inhibiting TRPV3 channels in mice.
Eur J Pharmacol
January 2025
Department of Pharmacology, School of Pharmacy, Qingdao Medical College of Qingdao University, Qingdao, China; Institute of Innovative Drugs, Qingdao University, Qingdao, China.
Dihydrotestosterone (DHT), an androgen derivate, is known to be a key factor involved in androgenetic alopecia. DHT suppresses the growth of outer root sheath cells and induces apoptosis of hair keratinocytes, thereby causing hair follicle miniaturization and hair regrowth inhibition. Forsythoside A, a natural substance derived from Forsythia suspensa, has been shown to reduce DHT-induced apoptosis in human hair cells and suppress hair regrowth inhibition induced by DHT in mice.
View Article and Find Full Text PDFSingle-cell Transcriptomics Reveals Intratumor Heterogeneity and the Potential Roles of Cancer Stem Cells and myCAFs in Colorectal Cancer Liver Metastasis and Recurrence.
Cancer Lett
January 2025
Department of Clinical Laboratory, The Second Hospital of Shandong University, 247 Beiyuan Street, Jinan, 250033, Shandong, China; Shandong Engineering & Technology Research Center for Tumor Marker Detection, Jinan, 250033, Shandong, China; Shandong Provincial Clinical Medicine Research Center for Clinical Laboratory, Jinan, 250033, Shandong, China. Electronic address:
Metastasis and recurrence are the primary obstacles to long-term survival in colorectal cancer (CRC) patients. In this study, we employed single-cell RNA sequencing (scRNA-seq) to comprehensively delineate the transcriptomic landscape of primary and liver metastatic CRCs, and revealed novel cellular crosstalk between cancer cell subpopulation and myofibroblastic CAFs (myCAFs) at single-cell resolution. We identified a cancer cell subpopulation termed stem/transient amplifying-like (stem/TA-like) cells, which expressed genes associated with stem cell-like characteristics and metastatic potential.
View Article and Find Full Text PDFFast Neuronal Calcium Signals in Brain Slices Loaded With Fluo-4 AM Ester.
Eur J Neurosci
January 2025
Université Grenoble Alpes, CNRS, LIPhy, Grenoble, France.
Staining brain slices with acetoxymethyl ester (AM) Ca dyes is a straightforward procedure to load multiple cells, and Fluo-4 is a commonly used high-affinity indicator due to its very large dynamic range. It has been shown that this dye preferentially stains glial cells, providing slow and large Ca transients, but it is questionable whether and at which temporal resolution it can also report Ca transients from neuronal cells. Here, by electrically stimulating mouse hippocampal slices, we resolved fast neuronal signals corresponding to 1%-3% maximal fluorescence changes.
View Article and Find Full Text PDFThe medial habenula (MHb)-interpeduncular nucleus (IPN) pathway plays an important role in information transferring between the forebrain and the midbrain. The MHb-IPN pathway has been implicated in the regulation of fear behavior and nicotine addiction. The synapses between the ventral MHb and the IPN show a unique property, i.
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!