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During muscle differentiation, mitochondria undergo dramatic changes in their morphology and distribution to prepare for the higher rate of energy consumption. By applying a mitochondria-targeted rosamine library in C2C12 myogenesis, we discovered one compound that controls muscle differentiation. When treated to undifferentiated myoblasts, our selected compound, B25, inhibited myotube formation, and when treated to fully differentiated myotubes, it induced fission of multinucleated myotubes into mononucleated fragments. Compared to myoseverin, which is known for inducing myotube fission by destabilizing microtubules, B25 affects neither microtubule stability nor cell cycle. Further investigation identified that B25 induces myotube fission through the activation of NF-κB, which is one of the important signaling pathways linked to skeletal muscle differentiation. So far, the use of small-molecule fluorophores is limited in the discovery of labeling agents or sensors. In addition to their potential as a sensor, here we show the application of fluorescent small molecules in the discovery of a bioactive probe that induces a specific cellular response. [ABSTRACT FROM AUTHOR]

To expand the diversity of 1,3,5-triazine libraries to aryl and alkyl functionalities through the C–C bond, we employed a novel orthogonal synthesis via Grignard monoalkylation or monoarylation of cyanuric chloride in solution to prepare aryl- or alkyl-substituted triazine building blocks. These aryl- or alkyl-substituted triazine building blocks were captured by a resin-bound amine, followed by amination and acidic cleavage with high purity. Herein, we demonstrate a novel orthogonal synthesis of a tagged aryl- and alkyl-triazine library on solid support, utilizing building blocks prepared via Grignard reaction in solution. Through incorporation of a triethylene glycol linker at one of the alternate sites on the triazine scaffold we explored an intrinsic tagged library approach. [ABSTRACT FROM AUTHOR]

Glycoprotein 90K (also known as LGALS3BP or Mac-2BP) is a tumor-associated protein, and high 90K levels are associated with poor prognosis in some cancers. To clarify the role of 90K as an indicator for poor prognosis and metastasis in epithelial cancers, the present study investigated the effect of 90K on an adherens junctional protein, E-cadherin, which is frequently absent or downregulated in human epithelial cancers. Treatment of certain cancer cells with 90K significantly reduced E-cadherin levels in a cell-population-dependent manner, and these cells showed decreases in cell adhesion and increases in invasive cell motility. Mechanistically, 90K-induced E-cadherin downregulation occurred via ubiquitination-mediated proteasomal degradation. 90K interacted with the E-cadherin-p120-catenin complex and induced its dissociation, altering the phosphorylation status of p120-catenin, whereas it did not associate with β-catenin. In subconfluent cells, 90K decreased membrane-localized p120-catenin and the membrane fraction of the p120-catenin. Particularly, 90K-induced E-cadherin downregulation was diminished in p120-catenin knocked-down cells. Taken together, 90K upregulation promotes the dissociation of the E-cadherin-p120-catenin complex, leading to E-cadherin proteasomal degradation, and thereby destabilizing adherens junctions in less confluent tumor cells. Our results provide a potential mechanism to explain the poor prognosis of cancer patients with high serum 90K levels. [ABSTRACT FROM AUTHOR]

Herein we report the solid-phase synthesis of a. combinatorial aryl, alkyl-triazine library and its application to biofuet production. The combination of Grignard reactions and solid supported .Suzuki coupling reactions afforded unique 120 triazine compounds with high purities and minimum purification steps. Through an unbiased phenotypic screening for improved biofuel generation m oleaginous yeast, we found one diaryl triazine derivative (E4) which increased the biolipid production up to 86%. [ABSTRACT FROM AUTHOR]

A major barrier to regeneration of CNS axons is the presence of growth-inhibitory proteins associated with myelin and the glial scar. To identify chemical compounds with the ability to overcome the inhibition of regeneration, we screened a novel triazine library, based on the ability of compounds to increase neurite outgrowth from cerebellar neurons on inhibitory myelin substrates. The screen produced four "hit compounds," which act with nanomolar potency on several different neuronal types and on several distinct substrates relevant to glial inhibition. Moreover, the compounds selectively overcome inhibition rather than promote growth in general. The compounds do not affect neuronal cAMP levels, PKC activity, or EGFR (epidermal growth factor receptor) activation. Interestingly, one of the compounds alters microtubule dynamics and increases microtubule density in both fibroblasts and neurons. This same compound promotes regeneration of dorsal column axons after acute lesions and potentiates regeneration of optic nerve axons after nerve crush in vivo. These compounds should provide insight into the mechanisms through which glial-derived inhibitors of regeneration act, and could lead to the development of novel therapies for CNS injury. [ABSTRACT FROM AUTHOR]

We report here a novel fluorescent chemical probe CDy5 which stains distinct neural stem/progenitor cells (NSPCs) by binding to acid ceramidase in mouse neurospheres. CDy5 is distributed evenly or unevenly to the daughter cells during multiple mitoses enabling the live imaging of symmetric and asymmetric divisions of isolated NSPCs. [ABSTRACT FROM AUTHOR]