PD198306 / Pfizer, Geisel School of Medicine at Dartmouth, University of Montreal - LARVOL DELTA

Bridging the Gap: Role of Serotonin on Cannabinoid Receptor Regulation (Neuroscience 2024) - "We also used either U73122, a phospholipase C Beta inhibitor, or PD198306, a MEK1/2 inhibitor, which are (+/-)DOI-activated signaling pathways in these cells. Preincubating cells with PD198306, but not U73122, prevented the DOI-induced CB1R upregulation in neuronal cells.In summary, our data identified regionally-specific regulation of brain cannabinoid receptors by cocaine and suggest a new mechanism by which 5-HT2A receptors would regulate the expression of cannabinoid receptors in neuronal cells."

CNS Disorders • Mental Retardation • Psychiatry

A Multistep In Silico Approach Identifies Potential Glioblastoma Drug Candidates via Inclusive Molecular Targeting of Glioblastoma Stem Cells. (PubMed, Mol Neurobiol) - "The growth inhibitory effect of these final shortlisted compounds was examined on a panel of GBM cell lines and compared with temozolomide through the drug sensitivity EC50 values and AUC from the PRISM Repurposing Secondary Screen, and the IC50 values were obtained from GDSC portal...Our results show GSK-2126458/omipalisib, linifanib, drospirenone, eltrombopag, nilotinib, and PD198306 as candidate drugs which can be further evaluated for their anti-tumor potential against GBM. Through this work, we identified repurposed candidate therapeutics against GBM utilizing a GSC inclusive targeting approach, which demonstrated high in vitro efficacy and can prospectively evade drug resistance. These drugs have the potential to be developed as individual or combination therapy to improve GBM outcomes."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor • PSMA2 • PSMC2 • RPA3

Multi-Omics Immune Interaction Networks in Lung Cancer Tumorigenesis, Proliferation, and Survival. (PubMed, Int J Mol Sci) - "From these networks, pan-sensitive and pan-resistant genes to 21 NCCN-recommended drugs for treating NSCLC were selected. Based on the gene associations with patient survival and in-vitro CRISPR-Cas9, RNAi, and drug screening data, MEK1/2 inhibitors PD-198306 and U-0126, VEGFR inhibitor ZM-306416, and IGF-1R inhibitor PQ-401 were discovered as potential targeted therapy that may also induce an immune response for treating NSCLC."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Small-molecule high-throughput screening identifies a MEK inhibitor PD1938306 that enhances sorafenib efficacy via MCL-1 and BIM in hepatocellular carcinoma cells. (PubMed, Comb Chem High Throughput Screen) - "The mechanistic research of the combination of sorafenib plus PD198306 showed that the two compounds synergistically inhibited MEK-ERK and mTORC1-4EBP1, and induced apoptosis in HCC cells, which can be attributed to the transcriptional and posttranslational regulation of MCL-1 and BIM. Conclusion Small-molecule qHTS identifies MEK inhibitor PD1938306 as a potent sorafenib enhancer, together with several novel combination strategies that are valuable for further studies."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • AURKB • BRAF • EGFR • EIF4EBP1 • MCL1

Characterization of Five Novel Anti-MRSA Compounds Identified Using a Whole-Animal Caenorhabditis elegans/Galleria mellonella Sequential-Screening Approach. (PubMed, Antibiotics (Basel)) - "Compound TBB showed synergistic activity with doxycycline and oxacillin against MRSA-MW2, and compounds PPT, NNC, GW4064, and PD198306 synergized with doxycycline, polymyxin-B, gentamicin, and erythromycin, respectively. The study demonstrates the utility of the multi-host approach with follow-up hit characterization for prioritizing anti-MRSA compounds for further evaluation."

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