YM-53601 / Astellas - LARVOL DELTA

FDFT1 maintains glioblastoma stem cells through activation of the Akt pathway. (PubMed, Stem Cell Res Ther) - "GSCs exhibit a dependency on FDFT1-mediated mevalonate metabolism. Inhibition of FDFT1 could represent a potent strategy to eliminate GSCs."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • FDFT1

Tumor-Suppressive Effect of Metformin via the Regulation of M2 Macrophages and Myeloid-Derived Suppressor Cells in the Tumor Microenvironment of Colorectal Cancer. (PubMed, Cancers (Basel)) - "The inhibitory effect of metformin and rapamycin on MDSCs and M2 macrophages was reversed by the co-treatment of Compound C (an AMP-activated protein kinase (AMPK) inhibitor) or mevalonate. To examine the effect of protein prenylation and cholesterol synthesis (the final steps of the mevalonate pathway) on the MDSC and M2 macrophage populations, we used respective inhibitors (YM53601; SQLE inhibitor, FTI-277; farnesyl transferase inhibitor, GGTI-298; geranylgeranyl transferase inhibitor) and found that the MDSC and M2 populations were suppressed by the protein prenylation inhibitors. In the DSS-treated Apc mouse colon cancer model, metformin reduced the number and volume of colorectal tumors with decreased populations of MDSCs and M2 macrophages in the tumor microenvironment. In conclusion, the inhibitory effect of metformin on MDSCs and M2 macrophages in the tumor microenvironment of colon cancers is mediated by AMPK activation and subsequent mTOR inhibition, leading to..."

Biomarker • Journal • Myeloid-derived suppressor cells • Tumor microenvironment • Colon Cancer • Colorectal Cancer • Diabetes • Gastrointestinal Cancer • Metabolic Disorders • Oncology • Solid Tumor • CD163 • CD33 • MRC1

Metformin Suppresses Cancer Stem Cells through AMPK Activation and Inhibition of Protein Prenylation of the Mevalonate Pathway in Colorectal Cancer. (PubMed, Cancers (Basel)) - "In both HT29 and DLD-1 cells, the CSC population was significantly decreased following treatment with metformin, AMPK activator (AICAR), HMG-CoA reductase inhibitor (simvastatin), or mTOR inhibitor (rapamycin), and was increased by mevalonate. Furthermore, in the MVA pathway, CSC populations were reduced by inhibition of protein prenylation with a farnesyl transferase inhibitor (FTI-277) or a geranylgeranyl transferase inhibitor (GGTI-298), but not by inhibition of cholesterol synthesis with a squalene synthase inhibitor (YM-53601). In conclusion, the CSC-suppressive effect of metformin was associated with AMPK activation and repression of protein prenylation through MVA pathway suppression in colorectal cancer."

Cancer stem cells • Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD133 • CD44

Discovery of a Small Molecule-Dependent Photolytic Peptide. (PubMed, J Am Chem Soc) - "It is likely that the radical species generated from UV-activated YM-53601 abstract hydro-gen atoms from the SQS peptide, leading to the photolysis of the entire protein. The pair of the SQS peptide and YM-53601 discovered in the present study paves the way for designing a new small-molecule-controlled optogenetic tool."

Journal