Melanoma is a type of cancer arising from the melanocytes, which are the cells that make up the pigment melanin and are derived from the neural crest. There is no particularly effective therapy once the disease is metastatic, highlighting the need for discovery of novel potent agents. In this investigation, we adopted a zebrafish embryonic pigmentation model to identify antimelanoma agents by screening an in-house small molecule library. With this assay, we found that a small molecule compound, SKLB226, blocked zebrafish pigmentation and pigment cell migration. Mechanism of action studies showed that SKLB226 downregulated MITF mRNA level in both zebrafish embryos and mammalian melanoma cells. Further studies showed that it could efficiently suppress the viability and migration of mammalian melanoma cells. In summary, SKLB226 can be used as a chemical tool to study melanocyte development as well as an antimelanoma lead compound that should be subjected to further structural optimization.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1097/CMR.0000000000000229 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Treatment of Seizures in People with Intellectual Disability.
CNS Drugs
January 2025
Cornwall Intellectual Disability Equitable Research (CIDER), University of Plymouth, Truro, England.
There is a synergistic relationship between epilepsy and intellectual disability (ID), and the approach to managing people with these conditions needs to be holistic. Epilepsy is the main co-morbidity associated with ID, and clinical presentation tends to be complex, associated with higher rates of treatment resistance, multi-morbidity and premature mortality. Despite this relationship, there is limited level 1 evidence to inform treatment choice for this vulnerable population.
View Article and Find Full Text PDFTowards effective functionalization of nanopores/nanochannels: the role of amidation reactions.
Chem Commun (Camb)
January 2025
State Key Laboratory of Biogeology and Environmental Geology, Engineering Research Center of Nano-Geomaterials of Ministry of Education, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan 430074, China.
In recent years, researchers have drawn inspiration from natural ion channels to develop various artificial nanopores/nanochannels, including solid-state and biological. Through imitating the precise selectivity and single molecule sensing exhibited by natural ion channels, nanopores/nanochannels have been widely used in many fields, such as analyte detection, gene sequencing and so on. In these applications, the surface functionalization of nanopores/nanochannels directly determines the effectiveness in quantitative analysis and single molecule detection.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
Indiana University, Indianapolis, IN, USA.
Background: Preclinical testing in animal models is a critical component of the drug discovery process. Over the past three decades hundreds of interventions have demonstrated preclinical efficacy for ameliorating cognitive impairments in animal models; however, none have translated to efficacy in Alzheimer's disease (AD) clinical trials. This lack of translation suggests that there are issues with the animal models employed, the preclinical assays, and poor scientific rigor and reproducibility during execution.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
Columbia University, New York, NY, USA.
Background: The connection between inflammasomes and Alzheimer's disease (AD) has garnered significant interest, with emerging evidence suggesting genetic associations and functional implications. Notably, studies have reported the upregulation of inflammasome components like NLRP1, NLRP3, and Caspase-1 in AD patients. Moreover, genetic polymorphisms in inflammasome-related genes are linked to increased AD risk.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
Tulane University, New Orleans, LA, USA.
Background: Alzheimer's Disease (AD) is a prevalent age-related neurodegenerative condition leading to dementia, yet factors regulating its polygenomic etiology and progression remain elusive. MicroRNAs (miRNAs), small RNA molecules regulating protein expression, play a role in neurodegeneration. MicroRNA-34a (miR-34a) is a crucial regulator of numerous genes associated with neurodegenerative disorders, protein aggregation and synaptic transmission genes.
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!