Abstract: The invention relates to treating a disease or condition in which it is desirable to inhibit 5?-methylthioadenosine phosphorylase (MTAP) and/or 5?-methylthioadenosine nucleosidase (MTAN). The invention particularly relates to the co-administration of 5?-methylthioadenosine (MTA), or a prodrug of MTA, with one or more MTAP/MTAN inhibitors. Included among the diseases treatable are prostate cancer and head and neck cancer.

Abstract: Provided are methods of designing a putative inhibitor of a 5?-methylthioadenosine/S-adenosylhomocysteine nucleosidase. The methods comprise designing a chemically stable compound that resembles the charge and geometry of the 5?-methylthioadenosine/S-adenosylhomocysteine nucleosidase transition state. Also provided are methods of inhibiting 5?-methylthioadenosine/S-adenosylhomocysteine nucleosidases using the inhibitors found by the above methods.

Abstract: This application provides fluorescent probes, substrates, kits and methods for detecting the presence or absence of an enzyme, such as ricin, that catalyzes the release of adenine from a GAGA RNA tetraloop.

Abstract: The present invention relates to compounds of the general formula (I) which are inhibitors of 5?-methylthioadenosine phosphorylase or 5?-methylthioadenosine nucleosidase. The invention also relates to the use of these compounds in the treatment of diseases or conditions in which it is desirable to inhibit 5?-methylthioadenosine phosphorylase or 5?-methylthioadenosine nucleosidase including cancer, and to pharmaceutical compositions containing the compounds.

Abstract: The invention relates to the treatment of cancer using an inhibitor of 5?-methylthioadenosine phosphorylase (MTAP). The invention particularly relates to the treatment of prostate cancer and head and neck cancer.

Abstract: Improved transition state analog inhibitors of ricin toxin-A are provided. Methods of using those inhibitors to inhibit ricin toxin-A and to prevent the toxic effects of ricin toxin-A in a mammal are also provided.

Abstract: Azetidine analogues of nucleosidase and nucleoside phosphorylase inhibitors having the general formula (I), the use of these compounds as pharmaceuticals, pharmaceutical compositions containing the compounds, methods of treating certain diseases using the compounds, processes for preparing the compounds, and intermediates useful in the preparation of the compounds wherein W and X are each independently selected from hydrogen, CH2OH, CH2OQ and CH2SQ; Y and Z are each independently selected from hydrogen, halogen, CH2OH, CH2OQ, CH2SQ, SQ, OQ and Q; Q is an alkyl, aralkyl or aryl group each of which may be optionally substituted with one or more substituents selected from hydroxy, halogen, methoxy, amino, or carboxy; R1 is a radical of the formula (II) or R1 is a radical of the formula (III) A is selected from N, CH and CR2, where R2 is selected from halogen, alkyl, aralkyl, aryl, OH, NH2, NHR3, NR3R4 and SR5, where R3, R4 and R5 are each alkyl, aralkyl or aryl groups optionally substituted with hydroxy or halog

Abstract: A novel compound, 2?/3?-O-acetyl-ADP-ribose, is provided. The compound is a mixture of the 2? and 3? regioisomers of O-acetyl-ADP ribose, and is formed nonenzymatically from 2?-O-acetyl-ADP-ribose, which is the newly discovered product of the reaction of Sir2 enzymes with acetylated peptides and NAD+. Analogs of 2?/3?-O-acetyl-ADP-ribose are also provided. Additionally, methods of preparing 2?/3?-O-acetyl-ADP-ribose, methods of determining whether a test compound is an inhibitor of a Sir2 enzyme, methods of detecting Sir2 activity in a composition, methods of deacetylating an acetylated peptide, and methods of inhibiting the deacetylation of an acetylated peptide are provided. Prodrugs of 2?/3?-O-acetyl-ADP-ribose are also provided.

Abstract: Provided are methods of designing a putative inhibitor of a human 5?-methylthioadenosine phosphorylase (MTAP). Also provided are methods of inhibiting a human MTAP.

Abstract: The invention relates to compounds of the formula (I), which are L-enantiomeric forms of nucleoside analogues, and to pharmaceutical compositions containing the compounds, methods of treating certain diseases, including cancer, bacterial infection, parasitic infection, and T-cell mediated diseases, using the compounds, processes for preparing the compounds, and intermediates useful in the preparation of the compounds.

Abstract: The present invention relates to compounds of the general formula (I) which are inhibitors of purine nucleoside phosphorylases (PNP), purine phosphoribosyltransferases (PPRT), 5?-methylthioadenosine phosphorylases (MTAP), 5?-methylthioadenosine nucleosidases (MTAN) and/or nucleoside hydrolases (NH). The invention also relates to the use of these compounds in the treatment of diseases and infections including cancer, bacterial infections, protozoal infections, and T-cell mediated disease and to pharmaceutical compositions containing the compounds.

Abstract: The present invention relates to compounds of the general formula (I) which are inhibitors of purine nucleoside phosphorylases (PNP), purine phosphoribosyltransferases (PPRT), 5?-methylthioadenosine phosphorylases (MTAP), 5?-methylthioadenosine nucleosidases (MTAN) and/or nucleoside hydrolases (NH). The invention also relates to the use of these compounds in the treatment of diseases and infections including cancer, bacterial infections, protozoal infections, and T-cell mediated disease and to pharmaceutical compositions containing the compounds.

Abstract: This invention relates to compounds that are analogues of coformycin, pharmaceutical compositions containing the compounds, and methods of using the compounds for treating protozoan parasite infections, especially malaria.

Abstract: The present invention relates to compounds of the general formula (I) which are inhibitors of purine muclioside phosphorylases (PNP), purine phosphoribosyltransferases (PPRT), 5?-methylthioadenosine phosphorylases (MTAP), 5?-methylthioadenosine mucliosidases (MTAN) and/or nucleoside hydrolases (NH). The invention also relates to the use of these compounds in the treatment of diseases and infections including cancer, bacterial infections, protozoal infections, and T-cell mediated disease and to pharmaceutical compositions containing the compounds.

Abstract: The present invention provides compounds having the formula: wherein A is chosen from a nitrogen-, oxygen-, or sulfur-linked aryl, alkyl, cyclic, or heterocyclic group; both B and C are hydrogen, or either B or C is a halogen, amino, or thiol group and the other of B or C is hydrogen; and D is a primary alcohol, a hydrogen, or an oxygen, nitrogen, carbon, or sulfur linked to phosphate, a phosphoryl group, a pyrophosphoryl group, or adenosine monophosphate through a phosphodiester or carbon-, nitrogen-, or sulfur-substituted phosphodiester bridge, or to adenosine diphosphate through a phosphodiester or carbon-, nitrogen-, or sulfur-substituted pyrophosphodiester bridge. The present invention also provides pharmaceutical compositions containing the above compounds, methods of using the above compounds as pharmaceuticals, and processes for preparing the above compounds.

Abstract: A novel compound, 2?/3?-O-acetyl-ADP-ribose, is provided. The compound is a mixture of the 2? and 3? regioisomers of O-acetyl-ADP ribose, and is formed nonenzymatically from 2?-O-acetyl-ADP-ribose, which is the newly discovered product of the reaction of Sir2 enzymes with acetylated peptides and NAD+. Analogs of 2?/3?-O-acetyl-ADP-ribose are also provided. Additionally, methods of preparing 2?/3?-O-acetyl-ADP-ribose, methods of determining whether a test compound is an inhibitor of a Sir2 enzyme, methods of detecting Sir2 activity in a composition, methods of deacetylating an acetylated peptide, and methods of inhibiting the deacetylation of an acetylated peptide are provided. Prodrugs of 2?/3?-O-acetyl-ADP-ribose are also provided.

Abstract: A novel compound, 2?/3?-O-acetyl-ADP-ribose, is provided. The compound is a mixture of the 2? and 3? regioisomers of O-acetyl-ADP ribose, and is formed nonenzymatically from 2?-O-acetyl-ADP-ribose, which is the newly discovered product of the reaction of Sir2 enzymes with acetylated peptides and NAD+. Analogs of 2?/3?-O-acetyl-ADP-ribose are also provided. Additionally, methods of preparing 2?/3?-O-acetyl-ADP-ribose, methods of determining whether a test compound is an inhibitor of a Sir2 enzyme, methods of detecting Sir2 activity in a composition, methods of deacetylating an acetylated peptide, and methods of inhibiting the deacetylation of an acetylated peptide are provided. Prodrugs of 2?/3?-O-acetyl-ADP-ribose are also provided.

Abstract: A process of preparing a compound of the formula (I) wherein B is chosen from OH, NH2, NHR, H or halogen; D is chosen from OH, NH2, NHR, H halogen or SCH3; R is an optionally substituted alkyl, aralkyl or aryl group; and Z is selected from OH, hydrogen, halogen, hydroxy, SQ or OQ, Q is an optionally substituted alkyl, aralkyl or aryl group; or a tautomer thereof; or a pharmaceutically acceptable salt thereof; or an ester thereof; or a prodrug thereof, which comprises reacting a compound of the formula (II) with an anion produced by abstraction of the bromine or iodine atom from a compound of formula (XIX), to form a compound of formula (XX) The compound of formula (XX) is N- and O-deprotected to obtain the compound of formula (I).

Abstract: The present invention provides compounds having the formula: wherein A is CH or N; B is chosen from OH, NH2, NHR, H or halogen; D is chosen from OH, NH2, NHR, H, halogen or SCH3; R is an optionally substituted alkyl, aralkyl or aryl group; and X and Y are independently selected from H, OH or halogen except that when one of X and Y is hydroxy or halogen, the other is hydrogen; and Z is OH or, when X is hydroxy, Z is selected from hydrogen, halogen, hydroxy, SQ or OQ, Q is an optionally substituted alkyl, aralkyl or aryl group; or a tautomer thereof; or a pharmaceutically acceptable salt thereof; or an ester thereof; or a prodrug thereof; and compounds having the formula: wherein A, X, Y, Z and R are defined for compounds of formula (I) where first shown above; E is chosen from CO2H or a corresponding salt form, CO2R, CN, CONH2, CONHR or CONR2; and G is chosen from NH2, NHCOR, NHCONHR or NHCSNHR; or a tautomer thereof, or a pharmaceutically acceptable salt thereof, or an ester thereof, or a prodrug the

Abstract: A process of preparing a compound of the formula (I) wherein B is chosen from OH, NH2, NHR, H or halogen; D is chosen from OH, NH2, NHR, H halogen or SCH3; R is an optionally substituted alkyl, aralkyl or aryl group; and Z is selected from OH, hydrogen, halogen, hydroxy, SQ or OQ, Q is an optionally substituted alkyl, aralkyl or aryl group; or a tautomer thereof; or a pharmaceutically acceptable salt thereof; or an ester thereof; or a prodrug thereof, which comprises reacting a compound of the formula (II) with an anion produced by abstraction of the bromine or iodine atom from a compound of formula (XIX), to form a compound of formula (XX) The compound of formula (XX) is N- and O-deprotected to obtain the compound of formula (I).