Phosphorylation of histones was observed at certain tyrosine residues which have not been associated with epigenetic modification. These sites include H2B Tyr37, H4 Tyr88 and Tyr 51 and H3 Tyr99. Kinases responsible for the phosphorylation as well as downstream genes regulated by such phosphorylation were also identified. Antibodies that are specific to such phosphorylated histones have been generated, which are useful for detecting the phosphorylation and related events. With such findings, the present disclosure provides compositions and methods for disease diagnosis, prognosis and therapy selection, in particular for cancer, obesity and diabetes.

H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE

H. Lee Moffitt Cancer Center and Research Institute

Phosphorylation of histones and uses thereof

The present invention relates to compounds of formula (I) or a pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, wherein X.sub.1, X.sub.2, X.sub.3, X.sub.4, X.sub.5, W.sub.1, W.sub.2, W.sub.3, and W.sub.4 are as described. The present invention relates generally to inhibitors of histone deacetylase and to methods of making and using them. In one aspect, the invention relates to selective HDAC3 inhibitors useful for protecting .beta.-cells and improving insulin resistance. The selective HDAC3 inhibitors are also useful for promoting cognitive function and enhancing learning and memory formation. Compounds of the invention are useful for treating, alleviating, and/or preventing various conditions, including for example, a metabolic disorder such as type 1 or type 2 diabetes, dyslipidemias, lipodystrophies, liver disease associated with metabolic syndrome, polycystic ovarian syndrome, or obesity; inflammatory disease; neurological disorder; a memory or cognitive function disorder/impairment; an extinction learning disorder; fungal disease or infection; viral disease or infection such as HIV; hematological disease; liver disease; lysosomal storage disease; or neoplastic disease in humans or animals. ##STR00001##

The General Hospital Corporation

The Broad Institute, Inc.

Inhibitors of histone deacetylase

The present application relates to thienopyrrole derivatives, compounds of Formulas (I) and (Ia), wherein R, R.sup.1, R.sup.2 and R.sup.3 are as defined in the specification, pharmaceutical compositions containing such compounds and to their use in therapy. The compounds of the application can be useful for inhibiting KDM1 and the prevention and/or treatment of cancer, infectious disease, or a disease characterized by aberration of cellular energy metabolism, e.g., obesity. ##STR00001##

histone/obezite

Phosphorylation of histones and uses thereof

Inhibitors of histone deacetylase

Thienopyrroles as histone demethylase inhibitors

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