Onyx Pharmaceuticals, Inc.

Rigel Pharmaceuticals, Incorporated

The Babraham Institute

Sylvia Braselmann

Donald G Payan

Dane A Goff

Len Stephens

Phillip Thomas Hawkins

Dane Goff

Disclosed embodiments concern polycyclic alkaloid compounds and methods for their use and synthesis. Particular embodiments concern polycyclic alkaloids having a fused, six-membered ring, while other embodiments concern polycyclic alkaloids having a fused, five-membered ring. Methods for making the polycyclic alkaloids are disclosed, as well as methods for their use as prophylactics or treatments for certain diseases. Also disclosed are pharmaceutical compositions comprising the polycyclic alkaloids and their use.

Synthesis of polycyclic alkaloids

Identification, characterization and expression of nucleotides that encode phosphatidylinositol-3&prime;kinase associated protein(s) that bind to the intermediate SH2 domain on the regulatory subunit of PI3K, p85, by the associated protein(s) C-terminal amino acids, and that exhibit a bromodomain are described, as well as methods of using such proteins for medical applications, including diagnosis and treatment cell growth disorders.

Nucleotide sequences that encode phosphatidylinositol-3&prime; kinase associated proteins and uses thereof

Identification, characterization and expression of nucleotides that encode phosphatidylinositol-3' kinase associated protein(s) that bind to the intermediate SH2 domain on the regulatory subunit of PI3K, p85, by the associated protein(s) C-terminal amino acids, and that exhibit a bromodomain are described, as well as methods of using such proteins for medical applications, including diagnosis and treatment cell growth disorders.

Nucleotide sequences that encode phosphatidylinositol-3' kinase

The present invention relates to the discovery, identification and characterization of nucleotides that encode the G protein regulated phosphatidylinositol-3' kinase, a heterodimeric enzyme which produces the intracellular messenger phosphatidylinositol (3,4,5)-triphosphate in response to activation of trimeric G protein-linked receptors. This novel protein, comprised of a catalytic subunit, p120, and a regulatory subunit, p101, is found in cells of hematopoietic origin and is involved in immune system responses which cause inflammation. The presence of p101 subunit is largely responsible for the dramatic stimulation of kinase activity in the presence of activated trimeric G proteins. The invention encompasses p101 and p120 nucleotides; host cell expression systems, p101 and p120 proteins, fusion proteins, polypeptides and peptides, antibodies to these proteins, transgenic animals that express a p101 or p120 transgene, or recombinant knock-out cells and animals that do not express the p101 or p120 gene, antagonists and agonists of the enzyme, and other compounds that modulate p101 or p120 gene expression or enzyme activity that can be used for diagnosis, drug screening, clinical trial monitoring, and/or the treatment of inflammatory disorders.

G-beta-gamma regulated phosphatidylinositol-3' kinase

The present invention relates to the discovery, identification and characterization of nucleotides that encode the G protein regulated phosphatidylinositol-3' kinase, a heterodimeric enzyme which produces the intracellular messenger phosphatidylinositol (3,4,5)-triphosphate in response to activation of trimeric G protein-linked receptors. This novel protein, comprised of a catalytic subunit, p120, and a regulatory subunit, p101, is found in cells of hematopoietic origin and is involved in immune system responses which cause inflammation. The presence of p101 subunit is largely responsible for the dramatic stimulation of kinase activity in the presence of activated trimeric G proteins. The invention encompasses p101 and p120 nucleotides, host cell expression systems, p101 and p120 proteins, fusion proteins, polypeptides and peptides, antibodies to these proteins, transgenic animals that express a p101 or p120 transgene, or recombinant knock-out cells and animals that do not express the p101 or p120 gene, antagonists and agonists of the enzyme, and other compounds that modulate p101 or p120 gene expression or enzyme activity that can be used for diagnosis, drug screening, clinical trial monitoring, and/or the treatment of inflammatory disorders.

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San Francisco, CA, United States of America

Sylvia Braselmann