Icahn School of Medicine at Mount Sinai

Mount Sinai School of Medicine

The J. David Gladstone Institutes

Ming-Ming Zhou

Michael H Ohlmeyer

Mitchell Goldfarb

Nilesh Zaware

Adam Vincek

Shiraz Mujtaba

Aneel K Aggarwal

Eric M Verdin

Melanie Ott

Claudia Kim

Guillermo Gerona-Navarro

Yoel Rodriguez-Fernandez

Patrizia Casaccia

Matthew Galsky

Sudeh Izadmehr

Chunyan Ren

A genus of bicyclic inhibitors of CBX chromodomains is disclosed. The compounds are of the following genus: in which A, E, and G represent carbon or nitrogen such that the compounds are indoles or benzimidazoles. A particular subgenus of 1,3-disubstituted-1,3-dihydro-2H-benzo[d]imidazol-2-imines is of the general formula: The compounds inhibit CBX proteins.

Bicyclic inhibitors of CBX chromodomains

Cyclic vinylogous amides of Formula I are disclosed The compounds are useful for treating diseases that arise from inappropriate activity of proteins containing an acetyl-lysine. The compositions comprise a genus of cyclic vinylogous amides that are inhibitors of bromodomain.

Cyclic vinylogous amides as bromodomain inhibitors

The present invention relates to methods of suppressing the transcriptional expression of one or more genes by methylating the chromatin histone proteins of the one or more genes. Specifically, a viral SET domain histone lysine mehtyltransferase (vSET or vSET-like protein) methylates lysine 27 of a gene's histone protein 3 (H3-K27) thereby suppressing the transcription of the gene.

Method of suppressing gene transcription through histone lysine methylation

This disclosure relates generally to compounds and compositions comprising one or more indole analogs. These compounds are useful for treating diseases associated with NF-kB and p53 activity, such as cancer and inflammatory diseases.

Small molecule transcription modulators of bromodomains

Cyclic vinylogous amides of Formula I are disclosed  The compounds are useful for treating diseases that arise from inappropriate activity of proteins containing an acetyl-lysine. The compositions comprise a genus of cyclic vinylogous amides that are inhibitors of bromodomain.

The present invention relates to methods of suppressing the transcriptional expression of one or more genes by methylating the chromatin histone proteins of the one or more genes. Specifically, a viral SET domain histone lysine methyltransferase (vSET or vSET-like protein) methylates lysine 27 of a gene's histone protein 3 (H3-K27) thereby suppressing the transcription of the gene.

The present invention provides the structural determination of a bromodomain determined by NMR spectroscopy. The present invention also provides a binding partner for the bromodomain. In addition, the present invention provides methodology for related drug discovery using high throughput drug screening or structure based rational drug design using the three-dimensional data.

ZA loops of bromodomains

The present invention provides fragments of SNT and FGFR which can form a binding complex that is amenable to structural determinations by NMR spectroscopy. The three-dimensional structural data is also included as part of the invention. In addition, the present invention provides methodology for related structure based rational drug design using the three-dimensional data. Nucleotide and amino acid sequences of the fragments are also provided.

Methods of indentifying modulators of the FGF receptor

The present invention provides the structural determination of a bromodomain determined by NMR spectroscopy. The present invention also provides binding partners for the bromodomain. The present invention further provides the structural determination of the Tat-P/CAF binding complex determined by NMR spectroscopy. In addition, the present invention provides methodology for related drug discovery using high throughput drug screening or structure based rational drug design using the three-dimensional data.

Growing community of inventors

Old Greenwich, CT, United States of America

Ming-Ming Zhou