Abstract: The present invention relates to methods and compositions for the detection, diagnosis, prevention and treatment of a disease, specifically cardiac, kidney or inflammatory disease, and related disorders. The present invention also relates to compositions and methods useful in the diagnosis, prevention and therapeutic treatment of a disease, specifically cardiac, kidney or inflammatory disease. Specifically, methods and compositions are provided for the diagnostic evaluation and prognosis of conditions involving a disease, specifically cardiac, kidney or inflammatory disease, for the identification of subjects exhibiting a predisposition to such conditions, for modulating the effect of these differentially expressed genes, for monitoring patients undergoing clinical evaluation for the prevention and treatment of a disease, specifically cardiac, kidney or inflammatory disease, and its disorders, and for monitoring the efficacy of compounds used in clinical trials.

Abstract: The invention concerns methods of treating fibroproliferative disorders associated with TGF-&bgr; signaling, by administering non-peptide small molecule inhibitors of TGF-&bgr; specifically binding to the type I TGF-&bgr; receptor (TGF&bgr;-R1). Preferably, the inhibitors are quinazoline derivatives. The invention also concerns methods for reversing the effect of TGF-&bgr;-mediated cell activation on the expression of a gene associated with fibrosis, comprising contacting a cell or tissue in which the expression of such gene is altered as a result of TGF-&bgr;-mediated cell activation, with a non-peptide small molecule inhibitor of TGF-&bgr;, specifically binding a TGF&bgr;-R1 receptor kinase present in the cell or tissue.

Abstract: The invention concerns the use of agonists and antagonists of peripheral-type benzodiazepine receptors (PTBR) in the diagnosis and treatment of cardiac hypertrophy and other circulatory conditions. The invention specifically concerns the use of PTBR antagonists in the prevention or treatment of decompensated cardiac hypertrophy and, eventually, heart failure. The invention also concerns the use of PTBR agonists in the management of conditions calling for increased blood flow or cardiac output, including injury or functional compromise of the heart, increased demand for physical exercise, or an acquired or inherited predisposition to cardiac contractile disfunction. Pharmaceutical compositions for the treatment of such conditions and screening methods to identify PTBR agonists and antagonists are also included.

Abstract: The invention concerns the prevention and treatment of endothelial injury and the injury of tissues containing injured blood vessels by administration of angiogenic factors, such as vascular endothelial cell growth factor (VEGF).

Abstract: The invention concerns the prevention and treatment of endothelial injury and the injury of tissues containing injured blood vessels by administration of angiogenic factors, such as vascular endothelial cell growth factor (VEGF).

Abstract: Indoles, benzimidazoles and benztriazoles which are substituted at the 5 or 6 position with a substituent comprising an aromatic moiety linked through a piperazine ring to said indole, benzimidazole or benztriazole are useful in treating cardiac conditions associated with heart failure and in treating conditions characterized by proinflammation.

Abstract: Methods and compositions for restoring diuretic and renal function

Abstract: The invention is directed to compounds of the formula 1

Abstract: The invention is directed to methods to inhibit TGF-&bgr;and/or p38-&agr; kinase using compounds of the formula 1

Abstract: The invention is directed to methods for treating conditions mediated by by P38&agr; kinase using compounds of the formula wherein Ar1 and Ph are limited to specific embodiments or wherein the compound of formula (3) is a compound set forth in FIGS. 1A-1T.

Abstract: The invention concerns the use of agonists and antagonists of peripheral-type benzodiazepine receptors (PTBR) in the diagnosis and treatment of cardiac hypertrophy and other circulatory conditions. The invention specifically concerns the use of PTBR antagonists in the prevention or treatment of decompensated cardiac hypertrophy and, eventually, heart failure. The invention also concerns the use of PTBR agonists in the management of conditions calling for increased blood flow or cardiac output, including injury or functional compromise of the heart, increased demand for physical exercise, or an acquired or inherited predisposition to cardiac contractile disfunction. Pharmaceutical compositions for the treatment of such conditions and screening methods to identify PTBR agonists and antagonists are also included.

Abstract: The invention concerns the use of ligands of peripheral-type benzodiazepine receptors (PTBR) in the diagnosis and treatment of diseases involving cyst formation and in particular polycystic kidney disease. The invention further concerns the treatment of hypertension accompanying polycystic kidney disease, and pharmaceutical compositions and articles of manufacture for the treatment or diagnosis of the target disease or condition.

Abstract: The present invention provides methods and compositions for treating hypertension. The methods generally involve administering a factor which increases angiogenesis and/or vascular permeability. Compositions for use in the methods are also provided.

Abstract: The invention is directed to methods to inhibit TGF-&bgr; and/or p38-&agr; kinase using compounds of the formula or the pharmaceutically acceptable salts thereof wherein R3 is a noninterfering substituent; each Z is CR2 or N, wherein no more than two Z positions in ring A are N, and wherein two adjacent Z positions in ring A cannot be N; each R2 is independently a noninterfering substituent; L is a linker; n is 0 or 1; and Ar′ is the residue of a cyclic aliphatic, cyclic heteroaliphatic, aromatic or heteroaromatic moiety optionally substituted with 1-3 noninterfering substituents.

Abstract: The invention is directed to methods to inhibit TGF-&bgr; and/or p38-&agr; kinase using compounds of the formula 1

Abstract: Compounds of the formula: wherein the dotted line represents an optional bond; and the pharmaceutically acceptable salts thereof, wherein X1 is an alkyl bridge optionally containing an O, S, or N heteroatom that forms an aliphatic 5-7 membered ring and is optionally substituted by one or more of halo, OR, SR, NR2, RCO, COOR, CONR2, OOCR, or NROCR where R is H or alkyl (1-6C), or by one or more CN or═O, or by one or more aliphatic or aromatic 5- or 6-membered rings optionally containing 1-2 heteroatoms; R1 is  wherein X2 is CO or an isostere thereof; m is 0 or 1; Y is optionally substituted alkyl, optionally substituted aryl, or optionally substituted arylalkyl or two Y taken together may form an alkylene (2-3C) bridge; n is 0-4; Z1 is CH or N; X3 is CH or CHR where R is H or alkyl (1-6C), or an isostere thereof; and Ar, R2 and R3 are as defined in the specification. These compounds are selective inhibitors of p38&agr; kinase.

Abstract: The invention is directed to prepare medicaments for treatment of and to methods to treat conditions mediated by kinase using compounds of the formula 1

Abstract: The invention is directed to methods to treat conditions mediated by p38-&agr;kinase using compounds of the formula and the pharmaceutically acceptable salts thereof, or a pharmaceutical composition thereof, wherein Z is N or CR1, R1 is a noninterfering substituent, each of X1 and X2 is a linker, Ar1 and Ar2 are identical or different, and represent optionally substituted C1-C20 hydrocarbyl residues wherein at least one of Ar1 and Ar2 is an optionally substituted aryl group, with the proviso that when X2 is CH2 or an isostere thereof, X1 is CO or an isostere thereof, and Ar2 is optionally substituted phenyl, Ar1 is other than an optionally substituted indolyl, benzimidazolyl or benzotriazolyl substituent, and wherein said optionally substituted phenyl is not an optionally substituted indolyl, benzimidazolyl, or benzotriazolyl, Y is a noninterfering substituent, wherein n is an integer from 0-4, and wherein m is an integer from 0-4 and 1 is an integer from 0-3.

Abstract: The invention concerns the use of ligands of peripheral-type benzodiazepine receptors (PTBR) in the diagnosis and treatment of diseases involving cyst formation and in particular polycystic kidney disease. The invention further concerns the treatment of hypertension accompanying polycystic kidney disease, and pharmaceutical compositions and articles of manufacture for the treatment or diagnosis of the target disease or condition.

Abstract: The present invention concerns methods for the treatment of salt-sensitive hypertension. The methods generally involve administering a vascular endothelial growth factor (VEGF) in an amount effective to reduce the blood pressure of a patient suffering from salt-sensitive hypertension to a normal range.