American Home Products Corporation

Wyeth

Millennium Pharmaceuticals Limited

Procept Corporation

Pfizer Corporation

Dana-farber-cancer Institute Inc.

Timothy D Ocain

Katherine L Molnar-Kimber

Craig E Caufield

David D Deininger

Susan Laurene Acton

Natalie Alysia Dales

Bing Guan

Alexandra E Gould

Amadeo A Failli

James A Brown

Michael A Patane

Richard M Soll

Guy A Schiehser

Paul Jeffrey Dollings

Michael E Solomon

Ellis L Reinherz

Raymond J Patch

Theresa M Sampo

John L Primeau

Lloyd M Garrick

Linda K Clayton

Alain Stricker-Krongrad

Cecilia M Bastos

Vivek J Kadambi

John J Huang

Steven K Vernon

Jeffrey I Krieger

Huai Gao

Provided are rapamycin conjugates which are useful as immunogenic molecules for the generation of antibodies specific for rapamycin, for measuring levels of rapamycin or derivatives thereof; for isolating rapamycin binding proteins; and detecting antibodies specific for rapamycin or derivatives thereof. This invention also provides a rapamycin specific monoclonal antibody.

Rapamycin conjugates and antibodies

Provided are rapamycin conjugates which are useful as immunogenic molecules for the generation of antibodies specific for rapamycin, for measuring levels of rapamycin or derivatives thereof; for isolating rapamycin binding proteins; and detecting antibodies specific for rapamycin or derivatives thereof. This invention also provides a rapamycin specific monclonal antibody.

Anti-rapamycin monoclonal antibodies

Rapamycin conjugates

Methods for identifying agents which enhance the activity of a caspase according to the invention are described, as well as methods for enhancing caspase activity and methods for enhancing apoptosis in a lymphocyte.

Methods of identifying agents which enhance caspase activity

ACE-2 inhibitors for the treatment of body weight and related disorders are disclosed. ACE-2 inhibitors include peptides and small molecules. Examples of small molecule ACE-2 inhibitors include compounds of formula (I):Z-&#x39b;&#x2003;&#x2003;(I)Wherein Z is a zinc coordinating moiety and &#x39b; is an amino-acid mimicking moiety, and pharmaceutically acceptabale salts thereof. Methods of using the inhibitors and pharmaceutical compositions containing the inhibitors to treat a body weight disorder, to decrease appetite, to increase muscle mass, to decrease body fat, to treat diabetes and to treat a state associated with altered lipid metabolism, are also described.

ACE-2 modulating compounds and methods of use thereof

ACE-2 inhibiting compounds and methods of use thereof

Provided are rapamycin conjugates which are useful as immunogenic molecules for the generation of antibodies specific for rapamycin or a derivative thereof, for measuring levels of rapamycin or derivatives thereof; for isolating rapamycin binding proteins; and detecting antibodies specific for rapamycin or derivatives thereof. This invention also provides monoclonal antibodies specific for rapamycin or a ring opened derivative of rapamycin.

Monoclonal antibodies obtained using rapamycin position 27 conjugates as an immunogen

Rapamycin position 27 conjugates

Novel compounds ##STR1## wherein R.sup.1 to R.sup.13 are independently selected from C.sub.2 -C.sub.4 linear and branched alkyls, H, NH.sub.2, CH.sub.3, OR.sup.14, fluorine, chlorine, iodine, NO.sub.2, CF.sub.3, NHCOCH.sub.3, NHCOOtBu, NHR.sup.15, NR.sup.16 R.sup.17 and phenyl, for use as immunosuppressive agents to prevent or significantly reduce graft rejection in organ and bone marrow transplantation are described. The novel compounds can also be used as an immunosuppressant drug for T-lymphocyte mediated autoimmune diseases, such as diabetes, and may be useful in alleviating psoriasis and contact dermatitis. Additionally, the novel compounds can be used for antiproliferation and gene therapy.

Aromatic compounds for inhibiting immune response

Use of ruthenium complexes as immunosuppressive agents to prevent or significantly reduce graft rejection in organ and bone marrow transplantation is described. The ruthenium complexes can also be used as immunosuppressant drugs for T-lymphocyte mediated autoimmune diseases, such as diabetes, and may be useful in alleviating psoriasis and contact dermatitis. The ruthenium complexes can also be used therapeutically in the treatment of hyperproliferative vascular disease.

Method for inhibiting immune response

A compound of the structure ##STR1## R.sup.1 and R.sup.2 are each, independently, hydrogen or ##STR2## X is ##STR3## Y is ##STR4## Z is --CH.sub.2 --, --S--S--, or ##STR5## R.sup.3 is hydrogen, alkyl, arylalkyl, alkenyl, alkynyl, --(CH.sub.2).sub.q CO.sub.2 R.sup.5, --(CH.sub.2).sub.r NR.sup.6 R.sup.7, carbamylalkyl, aminoalkyl, hydroxyalkyl, guanylalkyl, mercaptoalkyl, alkylthioalkyl, indolylmethyl, hydroxyphenylmethyl, imidazoylmethyl, halo, trifluoromethyl, or phenyl which is optionally mono-, di-, or tri-substituted;

Biotin esters of rapamycin

Compounds of the structure ##STR1## R and R.sup.1 are each, independently, hydrogen, or ##STR2## R.sup.2 and R.sup.3 are each, independently, alkyl, arylalkyl, or may be taken together to form a cycloalkyl ring;

Gem-distributed esters of rapamycin

There are disclosed compounds of the general formula I: ##STR1## wherein X is H, NR.sup.12 R.sup.13, OR.sup.14, CN, F, Cl, I, Br, perfluoroalkyl, alkyl, alkoxy, alkyl-OH, alkoxyalkyl, --(CH.sub.2).sub.n CO.sub.2 R.sup.14, --(CH.sub.2).sub.n CONR.sup.12 R.sup.13 ;

Pyrimidocycloalkanes as a II antagonists

A compound of the formula: ##STR1## wherein A is ##STR2## in which X is .dbd.CH-- or .dbd.N--; R.sup.2 is hydrogen, alkyl, phenyl, benzyl or phenethyl; Y is --CH.sub.2--, --NH-- or --O--; and Z is --H.sub.2 or .dbd.O; B is His, Leu, Ile, Nva, Nle, Ala or Val; and R.sup.1 is hydrogen, alkyl, phenyl or phenylalkyl; or a pharmaceutically acceptable salt thereof are renin inhibitors.

Renin inhibitors

A compound of the formula: ##STR1## wherein A is ##STR2## in which X is .dbd.CH-- or .dbd.N--; R.sup.2 is hydrogen, alkyl, phenyl, benzyl or phenethyl; Y is --CH.sub.2 --, --NH-- or --O--; and Z is --H.sub.2 or .dbd.O; B is His, Leu, Ile, Nva, Nle, Ala or Val; and R.sup.1 is hydrogen, alkyl, phenyl or phenylalkyl; or a pharmaceutically acceptable salt thereof are renin inhibitors.

Pyrrolimidazolones useful as renin inhibitors

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Framingham, MA, United States of America

Timothy D Ocain