New York University

Molsoft LLC

Herbert H Samuels

Dangsheng Li

Vandana Yajnik

Li Dangsheng

Sharmistha Das

Stephen R Wilson

Maxim Totrov

Ruben Abagyan

Harold Brem

Bruce M Raaka

Zhiguo Zhou

Marjana Tomic-Canic

Li Fan

Muktar A Mahajan

Matthieu Schapira

James Yopp, Jr

The present invention relates to methods and compositions that control, i.e., antagonize/inhibit or agonize/stimulate, de novo glucocorticoid production in the skin. Such methods and compositions can be used for the prevention and/or treatment of a variety of skin conditions, including inflammation, acute wounds, chronic non-healing wounds, keloid, fibrotic or hypertrophic scars, and epithelial-derived cancer.

De novo synthesis of glucocorticoids in the epidermis and its uses and applications

A method of identification of compounds that modulate thyroid hormone activity, and the use of such compounds and compositions thereof for such purposes are disclosed. The compounds may be selected from the group consisting of: The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of conditions that are causally related to aberrant thyroid hormone activity, such as hyperthyroidism and thyrotoxicosis.

Hydrazide compounds as thyroid hormone receptor modulators and uses thereof

Disclosed herein is the discovery that administration of the NRIF3 family of transcriptional coregulators (NRIF3 and related molecules) to breast cancer cells induce rapid and profound apoptosis (nearly 100% cell death within 24 h). A novel death domain (DD1) was mapped to a short 30 amino acid region common to all members of the NRIF3 family. Two other death domains (DD2 and DD3) were also found to have effective breast cancer killing activities. Mechanistic studies showed that DD1-induced apoptosis occurred through a novel caspase-2 mediated pathway that involved mitochondria membrane permeabilization but did not require other caspases. Interestingly, cytotoxicity of NRIF3 related molecules was cell-type specific, as they selectively killed breast cancer or related cells but not other examined cells of different origins, suggesting the presence in breast cancer cells of a specific death switch that can be selectively triggered by NRIF3 and related molecules. Also disclosed are strategies utilizing NRIF3 related molecules and/or targeting this death switch for the development of novel and more selective therapeutics against breast cancer.

Methods for treating breast cancer using NRIF3 related molecules

Nucleic acids encoding NRIF3 are described. Polypeptides having amino acid sequences of NRIF3 proteins are also provided. A method is also provided for isolating and cloning NRIF3 cDNA. NRIF3 is useful in development/implementation of high throughput screens to identify novel thyroid hormone receptor (TR) and retinoid X receptor (RXR) agonists and antagonists. Methods are also provided for identifying compounds that directly interfere with the interaction of NRIF3 and TR or RXR. Finally, therapies based on modulation of NRIF3 activity are disclosed.

Antibodies to NRIF3 proteins

NRIF3, a novel co-activator for nuclear hormone receptors

The present invention relates to isolated human and rat nucleic acid molecules encoding a protein or polypeptide that modulates transcriptional activation in a cell with or without collaboration with a nuclear hormone receptor transcriptional co-activator. The present invention also relates to the proteins or polypeptides encoded by those nucleic acid molecules, and antibodies against such proteins or polypeptides. The present invention also relates to a variety of uses for the nucleic acid molecules, proteins or polypeptides, and the related antibodies of the present invention, including methods of: regulating cellular proliferation, differentiation, and development; modulating the activity of a transcriptional co-activator complex and a transcription factor in cells; regulating hormone receptor activity and endocrine function in cells; and treating diabetes and insulin resistance in a subject.

Nucleic acid molecules encoding NRC interacting factor-1 (NIF-1)

The present invention relates to a method for detecting the post-translational modification of a target protein by a post translational modifier polypeptide molecule; a method for screening a candidate protein for E3 ligase activity; a method of screening a test compound for the ability to regulate the post-translational modification of a target protein by a post-translational modifier polypeptide molecule; and a method for the large-scale detection of candidate target proteins of post-translational modification by a modifier polypeptide molecule. The present invention also relates to a kit for determining whether a test protein is post-translationally modified by a modifier polypeptide molecule; a kit for screening a test compound for the ability to regulate the post-translational modification of a target protein by a post-translational modifier peptide molecule, and another kit for determining whether a test protein is post-translationally modified by a modifier polypeptide molecule.

Transcription-based assay for identification of post-translational modification and its application in proteomics

NRIF3, novel co-activator for nuclear hormone receptors

Growing community of inventors

New Rochelle, NY, United States of America

Herbert H Samuels