Publications by authors named "M Medvedovic"
In non-small cell lung cancer (NSCLC) treatment, radiotherapy responses are not durable and toxicity limits therapy. We find that AM-101, a synthetic benzodiazepine activator of GABA(A) receptor, impairs the viability and clonogenicity of both primary and brain-metastatic NSCLC cells. Employing a human-relevant ex vivo 'chip', AM-101 is as efficacious as docetaxel, a chemotherapeutic used with radiotherapy for advanced-stage NSCLC.
View Article and Find Full Text PDFArticle Synopsis
- The connectivity enhanced structure activity relationship (ceSAR) is a new in silico method for drug discovery that combines cheminformatics with transcriptional signature analysis from the LINCS library.* -
- ceSAR ranks drug candidates based on their similarity to known compounds and the impact on specific gene knockdowns, and then refines these ranks using molecular docking techniques and machine learning.* -
- Benchmark tests show that ceSAR significantly reduces false positives and speeds up the drug discovery process, with successful application in finding inhibitors for the BCL2A1 target linked to melanoma and inflammation.*
Unlabelled: Intrinsic resistance to targeted therapeutics in PTEN-deficient glioblastoma (GBM) is mediated by redundant signaling networks that sustain critical metabolic functions. Here, we demonstrate that coordinated inhibition of the ribosomal protein S6 kinase 1 (S6K1) and the receptor tyrosine kinase AXL using LY-2584702 and BMS-777607 can overcome network redundancy to reduce GBM tumor growth. This combination of S6K1 and AXL inhibition suppressed glucose flux to pyrimidine biosynthesis.
View Article and Find Full Text PDFBackground: Cardiac complications in patients with hypereosinophilia cause significant morbidity and mortality. However, mechanisms of how eosinophilic inflammation causes heart damage are poorly understood.
Methods: We developed a model of hypereosinophilia-associated heart disease by challenging hypereosinophilic mice with peptide from the cardiac myosin heavy chain.
Aberrant regulation of signal transduction pathways can adversely derail biological processes for tissue development. One such process is the embryonic eyelid closure that is dependent on the mitogen-activated protein kinase kinase kinase 1 (MAP3K1). Map3k1 KO in mice results in defective eyelid closure and an autosomal recessive eye-open at birth phenotype.
View Article and Find Full Text PDF