Abstract: The present invention provides novel compounds that can be used as antagonists of a lipid kinase such as a PI3 kinase, protein tyrosine kinase, and/or protein serine-threonine kinases such as mTOR. The present invention also provides methods of using the compounds for treating various disease conditions. The compounds include those having the formula: wherein the R1, R2 and R36 are as defined herein.

Abstract: This invention generally relates to pyrazolo pyrimidine derivatives useful as, inter alia, inhibitors of short chain dehydrogenase/reductase (SDR) family of NAD(P)(H) dependent oxido-reductases. More specifically, the invention relates to pyrazolo pyrimidine derivatives, including derivatives and analogs of SDR inhibitors, pharmaceutical compositions containing derivatives and analogs of SDR inhibitors, methods of making derivatives and analogs of SDR inhibitors and methods of use thereof.

Abstract: The present invention provides anti-inflammatory compounds useful in the treatment of diseases and conditions in which inflammation is involved in disease progression or the manifestation of symptoms of the disease or condition.

Abstract: The present invention provides novel mechanism-based crosslinkers useful in covalently linking a kinase and an interactor.

Abstract: This invention generally relates to pyrazolo pyrimidine derivatives useful as inhibitors of short chain dehydrogenase/reductase (SDR) family of NAD(P)(H) dependent oxido-reductases. The invention further relates to pharmaceutical compositions and methods of preventing or treating disease with 1H-Pyrrolo[2.3-d]pyrimidine derivatives. More specifically, the invention relates to a 1H-Pyrrolo[2.

Abstract: Engineered protein kinases which can utilize modified nucleotide triphosphate substrates that are not as readily utilized by the wild-type forms of those enzymes, and methods of making and using them are disclosed. Modified nucleotide triphosphate substrates and methods of making and using them are disclosed. Methods are disclosed for using such engineered kinases and such modified substrates to identify which protein substrates the kinases act upon, to measure the extent of such action, and to determine if test compounds can modulate such action. Engineered forms of multi-substrate enzymes which covalently attach part or all of at least one (donor) substrate to at least one other (recipient) substrate, which engineered forms will accept modified substrates that are not as readily utilized by the wild-type forms of those enzymes are disclosed. Methods for making and using such engineered enzymes are disclosed. Modified substrates and methods of making and using them are disclosed.

Abstract: The present invention provides a method for the identification of a pattern of changes in cellular responses induced by the selective inhibition of a signaling molecule, by determining the specific effects of a selective inhibitor on a mutant form of a signaling molecule on cellular responses. The pattern of alterations in cellular responses resulting from the inhibition by a selective mutant inhibitor of the mutant signaling molecule are characteristic of the cellular response alterations that a specific inhibitor of the wild-type signaling molecule will produce. After determining the pattern of cellular responses of the mutant cells with the mutant molecule, compounds may be identified capable of inhibiting the wild-type molecule by producing a pattern of cellular responses in wild-type cells matching or having similarity to that of the inhibition of the mutant molecule.

Abstract: This invention provides general methods for discovering mutant inhibitors for any class of enzymes as well as the specific inhibitors so identified. More specifically, this invention provides general methods for discovering specific inhibitors for multi-substrate enzymes. Examples of such multi-substrate enzymes include, but are not limited to, kinases and transferases. The mutant inhibitors identified by the methods of this invention can be used to highly selectively disrupt cell functions such as oncogenic transformation. In one particular example, this invention provides a Src protein kinase inhibitor, pharmaceutical compositions thereof and methods of disrupting transformation in a cell that expresses the target v-scr comprising contacting the cell with the protein kinase inhibitor.

Abstract: Engineered protein kinases which can utilize modified nucleotide triphosphate substrates that are not as readily utilized by the wild-type forms of those enzymes, and methods of making and using them are disclosed. Modified nucleotide triphosphate substrates and methods of making and using them are disclosed. Methods are disclosed for using such engineered kinases and such modified substrates to identify which protein substrates the kinases act upon, to measure the extent of such action, and to determine if test compounds can modulate such action. Engineered forms of multi-substrate enzymes which covalently attach part or all of at least one (donor) substrate to at least one other (recipient) substrate, which engineered forms will accept modified substrates that are not as readily utilized by the wild-type forms of those enzymes are disclosed. Methods for making and using such engineered enzymes are disclosed. Modified substrates and methods of making and using them are disclosed.

Abstract: The invention relates to methods for designing inhibitors of serine/theronine kinases and tyrosine kinases, particularly MAP kinases, through the use of ATP-binding site mutants of those kinases. The methods of this invention take advantage of the fact that the mutant kinases are capable of binding inhibitory compounds of other kinases with greater affinity than the corresponding wild-type kinase. The invention further relates to the mutant kinases themselves and crystallizable co-complexes of the mutant kinase and the inhibitory compound.

Abstract: Engineered protein kinases which can utilize modified nucleotide triphosphate substrates that are not as readily utilized by the wild-type forms of those enzymes, and methods of making and using them. Modified nucleotide triphosphate substrates and methods of making and using them. Methods for using such engineered kinases and such modified substrates to identify which protein substrates the kinases act upon, to measure the extent of such action, and to determine if test compounds can modulate such action. Also engineered forms of multi-substrate enzymes which covalently attach part or all of at least one (donor) substrate to at least one other (recipient) substrate, which engineered forms will accept modified substrates that are not as readily utilized by the wild-type forms of those enzymes. Methods for making and using such engineered enzymes. Modified substrates and methods of making and using them.

Abstract: This invention provides general methods for discovering mutant inhibitors for any class of enzymes as well as the specific inhibitors so identified. More specifically, this invention provides general methods for discovering specific inhibitors for multi-substrate enzymes. Examples of such multi-substrate enzymes include, but are not limited to, kinases and transferases. The mutant inhibitors identified by the methods of this invention can be used to highly selectively disrupt cell functions such as oncogenic transformation. In one particular example, this invention provides a Src protein kinase inhibitor, pharmaceutical compositions thereof and methods of disrupting transformation in a cell that expresses the target v-scr comprising contacting the cell with the protein kinase inhibitor.

Abstract: Engineered protein kinases which can utilize modified nucleotide triphosphate substrates that are not as readily utilized by the wild-type forms of those enzymes, and methods of making and using them. Modified nucleotide triphosphate substrates and methods of making and using them. Methods for using such engineered kinases and such modified substrates to identify which protein substrates the kinases act upon, to measure the extent of such action, and to determine if test compounds can modulate such action. Also Engineered forms of multi-substrate enzymes which covalently attach part or all of at least one (donor) substrate to at least one other (recipient) substrate, which engineered forms will accept modified substrates that are not as readily utilized by the wild-type forms of those enzymes. Methods for making and using such engineered enzymes. Modified substrates and methods of making and using them.