RapaLink-1, a Third-Generation Bivalent mTOR Inhibitor, Combines Rapamycin with MLN0128
Glioblastoma (GBM), the most common primary brain tumor, represents one of the most aggressive cancers. The signaling from PI3K and AKT to mTOR is commonly dysregulated in GBM. But, blockade of these upstream targets minimally affects mTOR activity in glioma. Allosteric mTOR inhibitors, such as rapamycin, incompletely block mTORC1...
AMG-458 is a Selective and Orally Bioavailable c-Met Inhibitor
C-met is a protein encoded by a met gene in humans, which has tyrosine kinase activity. Specifically, Met is an essential one-way tyrosine kinase receptor for embryonic development, organogenesis, and wound healing. Besides, C-met is a receptor tyrosine kinase that can be activated by its ligand, hepatocyte growth factor/dispersion...
JCN037 is a Non-Covalent and Brain-Penetrant EGFR Inhibitor
The epidermal growth factor receptor (EGFR) is a transmembrane protein that is a receptor for members of the EGF family of extracellular protein ligands. In many cancer types, mutations affecting EGFR expression or activity could result in cancer. Specifically, EGFR gene changes occurred in nearly 60% of glioblastoma tumors....
TED-347 is an Irreversible and Covalent YAP-TEAD Protein-Protein Interaction Inhibitor
Yap1, also known as Yap, is a protein that acts as a transcription regulator by activating the transcription of genes involved in cell proliferation and inhibiting apoptosis. Specifically, Yap1 is inhibited in the hippopotamus signaling pathway, which can control organ size and inhibit tumors. Besides, hippopotamus signaling regulates Yap1...
AMG 511 is an Orally Active pan-PI3K Inhibitor
The PI3K signaling network has a central role in several cellular processes critical to the initiation and progression of cancer, including growth, survival, and metabolism. The PI3K family catalyzes the phosphorylation of phosphatidylinositol-4,5-diphosphate to phosphatidylinositol-3,4,5-triphosphate, a secondary messenger that plays a critical role in important cellular functions such as...
TCH-165, a Proteasome Assembly Modulator, Regulates the Dynamic Equilibrium between the 20S and 26S Proteasome Complexes
Intrinsically disordered proteins (IDPs) involves a number of multiple regulatory and signaling events. In addition, the accumulation of IDPs results in some harmful signals happening in the pathogenesis of many human diseases. The proteasome contains different include active complexes (such as the 26S proteasome) and a weakly active complex: the...
M8891 is an Orally Active and Brain Penetrant MetAP-2 Inhibitor
Removal of N-terminal methionine by methionine aminopeptidases (MetAP) is a crucial step in the maturation of proteins during protein biosynthesis. Besides, MetAP-2 is one of the two cytoplasmic methionine aminopeptidases expressed in mammalian cells. Moreover, MetAP-2 acts as a target of the highly potent and irreversible inhibitor fumagillin to...