The present disclosure relates to compounds that bind to at least one of ACAT1/2 and OXCT1/2 and inhibit mitochondrial ATP production, referred to herein as mitoketoscins. Methods of screening compounds for mitochondrial inhibition and anti-cancer properties are disclosed. Also described are methods of using mitoketoscins to prevent or treat cancer, bacterial infections, and pathogenic yeast, as well as methods of using mitoketoscins to provide anti-aging benefits. Specific mitoketoscin compounds are also disclosed.

A repeat expansion in C90RF72 causes frontotemporal dementia and amyotrophic lateral sclerosis (c9FTD/ALS). RNA of the expanded repeat (r(GGGGCC).sub.exp) forms nuclear foci or undergoes repeat-associated non-ATG (RAN) translation producing “c9RAN proteins”. Since neutralizing r(GGGGCC).sub.exp could inhibit these potentially toxic events, we sought to identify small molecule binders of r(GGGGCC)exp, Chemical and enzymatic probing of r(GGGGCC).sub.8 indicate it adopts a hairpin structure in equilibrium with a quadruplex structure, Using this model, bioactive small molecules targeting r(GGGGCC).sub.exp were designed arid found to significantly inhibit RAN translation and foci formation in cultured cells expressing r(GGGGCC).sub.66 and neurons trans-differentiated from fibroblasts of repeat expansion carriers. Finally, we show that poly(GP) c9RAN proteins are specifically detected in c9ALS patient cerebrospinal fluid. Our findings highlight r(GGGGCC).sub.exp-binding small molecules as a possible C9FTD/ALS therapeutic, and suggest c9RAN proteins could potentially serve as a pharmacodynamic biomarker to assess efficacy of therapies that target r(GGGGCC).sub.exp.

The present invention relates to a method for detecting renal disease and for assessing the efficacy of dialysis treatment using imaging agents having desirable in vivo properties.

The present invention relates to a method for detecting renal disease and for assessing the efficacy of dialysis treatment using imaging agents having desirable in vivo properties.

The present invention discloses oxindole compounds and a single step, one pot reaction for the synthesis of oxindole derivates via a solvent free Passerini reaction of isocyanides, isatins and carboxylic acids.

The present invention discloses oxindole compounds and a single step, one pot reaction for the synthesis of oxindole derivates via a solvent free Passerini reaction of isocyanides, isatins and carboxylic acids.

Methods are provided for modulating MRGPRX2 generally, or for treating a MRGPRX2 dependent condition more specifically, by contacting the MRGPRX2 or administering to a subject in need thereof, respectively, an effective amount of a compound having structure (I): ##STR00001##
or a pharmaceutically acceptable salt, isomer, hydrate, solvate or isotope thereof, wherein A, B, C, D, E, G, W, Y, Z, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7 and R.sup.8 are as defined herein. Pharmaceutical compositions containing such compounds, as well as the compounds themselves, are also provided.

The invention relates to substituted heterocyclic indole derivatives of Formula (I), which act as activators of the AMP-activated protein kinase (AMPK) and to the use of them for the treatment and prevention of diseases or disorders regulated by AMPK. As a result, these compounds can be used for the treatment of inflammatory, autoimmune, cardiovascular, neurological diseases and cancer.

The invention relates to substituted heterocyclic indole derivatives of Formula (I), which act as activators of the AMP-activated protein kinase (AMPK) and to the use of them for the treatment and prevention of diseases or disorders regulated by AMPK. As a result, these compounds can be used for the treatment of inflammatory, autoimmune, cardiovascular, neurological diseases and cancer.

The present invention relates to inhibitors of histone deacetylases, in particular HDAC8, that are useful for the treatment of cancer and other diseases and disorders, as well as the synthesis and applications of said inhibitors.