Janssen Pharmaceutica Nv

Other

Ortho-mcneil Pharmaceutical Corp.

Bruce L Grasberger

Frank A Lewandowski

Cynthia M Milligan

Richard Scott Alexander

Celine Schalk-Hihi

Carsten Schubert

Diane M Maguire

Tianbao Lu

Maxwell David Cummings

Daniel J Parks

Karen L Milkiewicz

Raul R Calvo

John Curtis Spurlino

Alexander J Kim

Ingrid Christa Deckman

Louis V LaFrance

Theodore E Carver, Jr

Diane Maguire

Frank A Lewandoswki

A number of soluble engineered forms of MGLL that are suitable for high-throughput screening and protein crystallization, as well as a crystallized form of monoacylglycerol lipase protein (MGLL) and descriptions of the X-ray diffraction patterns are disclosed. The engineered constructs of MGLL permit the expression and purification of protein suitable for crystallography or high-throughput screening and identification of ligands, which can function as active agents to MGLL. The X-ray diffraction patterns allow the three dimensional structure of MGLL to be determined at atomic resolution so that ligand binding sites on MGLL can be identified and the interactions of ligands with MGLL amino acid residues can be modeled. Models prepared using such maps permit the design of ligands which can function as active agents which include, but are not limited to, those that function as inhibitors of MGLL.

Protein engineering of monoacylglycerol lipase (MGLL)

Crystal structure of monoacylglycerol lipase (MGLL)

A number of soluble engineered forms of MGLL that are suitable for high-throughput screening and protein crystallization, as well as a crystallized forms of monoacylglycerol lipase protein (MGLL) and descriptions of the X-ray diffraction patterns are disclosed. The engineered constructs of MGLL permit the expression and purification of protein suitable for crystallography or high-throughput screening and identification of ligands, which can function as active agents to MGLL. The X-ray diffraction patterns allow the three dimensional structure of MGLL to be determined at atomic resolution so that ligand binding sites on MGLL can be identified and the interactions of ligands with MGLL amino acid residues can be modeled. Models prepared using such maps permit the design of ligands which can function as active agents which include, but are not limited to, those that function as inhibitors of MGLL.

Alternative crystal form of monoacylglycerol lipase (MGLL)

The present invention includes crystallized HDM2 peptides as well as descriptions of the X-ray diffraction patterns of the crystals. The diffraction patterns allow the three dimensional structure of HDM2 to be determined at atomic resolution so that ligand binding sites on HDM2 can be identified and the interactions of ligands with HDM2 amino acid residues can be modeled. Models prepared using such maps permit the design of ligands which can function as active agents which include, but are not limited to, those that function as inhibitors of MDM2 and HDM2 oncoproteins.

HDM2-inhibitor complexes and uses thereof

The present invention is directed to novel 1,4-benzodiazepines, pharmaceutical compositions thereof, and the use thereof as inhibitors of HDM2-p53 interactions. Compounds have Formula I: or a solvate, hydrate or pharmaceutically acceptable salt thereof; wherein:

Substituted 1,4-benzodiazepines and uses thereof

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Trappe, PA, United States of America

Bruce L Grasberger