Smithkline Beecham Corporation

Ariad Pharmaceuticals, Inc.

Ariad Gene Therapeutics, Inc.

Smithkline Beckman Corporation

Other

Dennis Alan Holt

Mark A Levy

Brian W Metcalf

Wu Yang

Terence P Keenan

Leonard W Rozamus

Michael Z Gilman

Timothy P Clackson

Tao Guo

Edgardo Laborde

Juan I Luengo

Leonard Walter Rozamus, Jr

Cheryl A Digits

Conrad John Kowalski

Ann Marie Tickner

Hye-Ja Oh

Mark J Zoller

Jennifer L Karas

Xiaode Lu

Marcos H Hatada

Ellen R Laird

New compounds are disclosed for multimerizing immunophilins and proteins containing immunophilin or immunophilin-related domains. The compounds are of the formulaM-L-Qwhere M is a synthetic ligand for an FKBP protein.

Synthetic multimerizing agents

Methods and materials involving 28-epirapamycin analogs are disclosed.

28-epirapalogs

Rapamycin derivatives containing substituents at C-28 in the epi orientation relative to rapamycin are disclosed, together with methods for their preparation and use, e.g. for regulation of biological phenomena in engineered cells. The compounds may contain optional additional modifications relative to rapamycin, as disclosed herein.

Materials and method for treating or preventing pathogenic fungal infection

Materials and methods are disclosed for regulation of biological events such as target gene transcription and growth, proliferation or differentiation of engineered cells.

Regulation of biological events using novel compounds

This invention concerns new configurations for biological switches and provides new methods and materials useful for regulating biological events in animal cells. The invention involves recombinant DNA constructs comprising DNA sequences derived from sequences encoding the proteins FRAP, Tor1, Tor2 and other proteins capable of binding to FKBP:rapamycin, other recombinant DNA constructs comprising DNA sequences encoding part or all of an FKBP protein, the proteins encoded by those constructs, cells (especially animal cells) transformed with one or more of the constructs, small molecules (multivalent multimerizing agents) which bind to and are capable of inducing multimerization of the chimeric proteins, and methods for preparing and using the foregoing, including methods involving the intramuscular delivery of such recombinant DNA constructs in AAV virus particles.

Intramuscular delivery of recombinant AAV

Rapamycin derivatives; pharmaceutical compositions comprising such rapamycin derivatives and pharmaceutically acceptable carriers or diluents; and methods of using such derivatives to inhibit pathogenic fungi growth, inhibit immunosuppression or treat carcinogenic tumors are disclosed.

Rapamycin derivatives

This invention concerns derivatives of rapamycin and their antifungal uses. Also disclosed are materials and methods relevant to the identification of non-immunosuppressive antifungal rapamycin derivatives.

The invention relates to human ZAP-70, and in particular, to the region of ZAP-70 containing the tandem Src homology-2 (&ldquo;SH2&rdquo;) domains, to crystalline forms thereof, liganded or unliganded, which are particularly useful for the determination of the three-dimensional structure of the protein. The three dimensional structure of the tandem SH2 region of ZAP provides information useful for the design of pharmaceutical compositions which inhibit the biological function of ZAP and other members of the ZAP family of SH2 domain-containing proteins, particularly those biological functions mediated by molecular interactions involving one or both SH2 domains.

Three dimensional structure of a ZAP tyrosine protein kinase fragment and modeling methods

New compounds are disclosed for multimerizing immunophilins and proteins containing immunophilin or immunophilin-related domains. The compounds are of the formula

Growing community of inventors

Stow, MA, United States of America

Dennis Alan Holt