Abstract: The present invention includes a crystal comprising a complex of the pro form of a matrix metalloprotease (proMMP) and a small-molecule allosteric processing inhibitor that inhibits that activation of the proMMP, methods for identifying small-molecule allosteric processing inhibitors that inhibit the activation of a proMMP, and methods of treatment using small-molecule allosteric processing inhibitors that inhibit the activation of a proMMP. The present invention relates to the crystal structure of a complex of proMMP9 bound to a small-molecule allosteric processing inhibitor that inhibits activation of proMMP9. The invention further relates to the use of the methods and the crystal and related structural information for designing, selecting and/or optimizing small-molecule allosteric processing inhibitors that inhibit activation of proMMP9 and proMMP9 homologues.

Abstract: The present invention includes a crystal comprising a complex of the pro form of a matrix metalloprotease (proMMP) and a small-molecule allosteric processing inhibitor that inhibits that activation of the proMMP, methods for identifying small-molecule allosteric processing inhibitors that inhibit the activation of a proMMP, and methods of treatment using small-molecule allosteric processing inhibitors that inhibit the activation of a proMMP. The present invention relates to the crystal structure of a complex of proMMP9 bound to a small-molecule allosteric processing inhibitor that inhibits activation of proMMP9. The invention further relates to the use of the methods and the crystal and related structural information for designing, selecting and/or optimizing small-molecule allosteric processing inhibitors that inhibit activation of proMMP9 and proMMP9 homologues.

Abstract: The present invention includes a crystal comprising a complex of the pro form of a matrix metalloprotease (proMMP) and a small-molecule allosteric processing inhibitor that inhibits that activation of the proMMP, methods for identifying small-molecule allosteric processing inhibitors that inhibit the activation of a proMMP, and methods of treatment using small-molecule allosteric processing inhibitors that inhibit the activation of a proMMP. The present invention relates to the crystal structure of a complex of proMMP9 bound to a small-molecule allosteric processing inhibitor that inhibits activation of proMMP9. The invention further relates to the use of the methods and the crystal and related structural information for designing, selecting and/or optimizing small-molecule allosteric processing inhibitors that inhibit activation of proMMP9 and proMMP9 homologues.

Abstract: Disclosed are compounds, compositions and methods for treating diseases, syndromes, conditions and disorders that are affected by the inhibition of MGL, including pain. Such compounds are represented by Formula (I) as follows: wherein R1, W and are defined herein.

Abstract: A method for identifying a ligand or compound which binds to albumin comprises the steps of contacting a reaction mixture comprising a site-specific probe and albumin in the presence and the absence of the ligand or compound and measuring either dissociation constant KD, inhibitor concentration IC50 or fluorescence displacement; whereby a change in KD, IC50 and/or fluorescence in the presence of the ligand or compound is indicative of the ligand or compound binds to albumin.

Abstract: The present invention includes a crystal comprising a complex of the pro form of a matrix metalloprotease (proMMP) and a small-molecule allosteric processing inhibitor that inhibits that activation of the proMMP, methods for identifying small-molecule allosteric processing inhibitors that inhibit the activation of a proMMP, and methods of treatment using small-molecule allosteric processing inhibitors that inhibit the activation of a proMMP. The present invention relates to the crystal structure of a complex of proMMP9 bound to a small-molecule allosteric processing inhibitor that inhibits activation of proMMP9. The invention further relates to the use of the methods and the crystal and related structural information for designing, selecting and/or optimizing small-molecule allosteric processing inhibitors that inhibit activation of proMMP9 and proMMP9 homologues.

Abstract: The present invention includes a crystal comprising a complex of the pro form of a matrix metalloprotease (proMMP) and a small-molecule allosteric processing inhibitor that inhibits that activation of the proMMP, methods for identifying small-molecule allosteric processing inhibitors that inhibit the activation of a proMMP, and methods of treatment using small-molecule allosteric processing inhibitors that inhibit the activation of a proMMP. The present invention relates to the crystal structure of a complex of proMMP9 bound to a small-molecule allosteric processing inhibitor that inhibits activation of proMMP9. The invention further relates to the use of the methods and the crystal and related structural information for designing, selecting and/or optimizing small-molecule allosteric processing inhibitors that inhibit activation of proMMP9 and proMMP9 homologues.

Abstract: The present invention includes a crystal comprising a complex of the pro form of a matrix metalloprotease (proMMP) and a small-molecule allosteric processing inhibitor that inhibits that activation of the proMMP, methods for identifying small-molecule allosteric processing inhibitors that inhibit the activation of a proMMP, and methods of treatment using small-molecule allosteric processing inhibitors that inhibit the activation of a proMMP. The present invention relates to the crystal structure of a complex of proMMP9 bound to a small-molecule allosteric processing inhibitor that inhibits activation of proMMP9. The invention further relates to the use of the methods and the crystal and related structural information for designing, selecting and/or optimizing small-molecule allosteric processing inhibitors that inhibit activation of proMMP9 and proMMP9 homologues.

Abstract: A method for identifying a ligand or compound which binds to albumin comprises the steps of contacting a reaction mixture comprising a site-specific probe and albumin in the presence and the absence of the ligand or compound and measuring either dissociation constant KD, inhibitor concentration IC50 or fluorescence displacement; whereby a change in KD, IC50 and/or fluorescence in the presence of the ligand or compound is indicative of the ligand or compound binds to albumin.

Abstract: The present invention provides a method of rapidly screening ligands on the basis of their binding affinity and binding enthalpy by carrying out binding assays at a minimum of two temperatures. This technique permits the selection for further optimization of lead ligands that bind to the target molecules with favorable enthalpies. Those ligands will exhibit higher solubilities in aqueous solution than ligands selected by conventional means, and may exhibit lower susceptibilities to resistant mutations. The method may be utilized as a standalone technique, or may be adapted to, for example, known high throughput screening technologies. The present invention further comprises an apparatus for carrying out the described methods.

Abstract: The present invention provides a method of rapidly screening ligands on the basis of their binding affinity and binding enthalpy by carrying out binding assays at a minimum of two temperatures. This technique permits the selection for further optimization of lead ligands that bind to the target molecules with favorable enthalpies. Those ligands will exhibit higher solubilities in aqueous solution than ligands selected by conventional means, and may exhibit lower susceptibilities to resistant mutations. The method may be utilized as a standalone technique, or may be adapted to, for example, known high throughput screening technologies. The present invention further comprises an apparatus for carrying out the described methods.