Abstract: A hydrogel material for modulating an immune response in a human subject or other mammal includes a collection of microgel particles having one or more network cross linker components, wherein the microgel particles, when exposed to an endogenous or exogenous annealing agent, links the microgel particles together in situ to form a covalently-stabilized scaffold of microgel particles having interstitial spaces formed between the microgel particles and wherein the collection of microgel particles further includes at least one of an antigen and an adjuvant.

Abstract: A hydrogel material for use in a human subject or other mammal includes a collection of microgel particles having one or more network cross linker components, wherein the microgel particles, when exposed to an endogenous or exogenous annealing agent, links the microgel particles together in situ to form a covalently-stabilized scaffold of microgel particles having pores formed between the microgel particles wherein the pores are substantially devoid of hydrogel.

Abstract: Inhibition of indoleamine 2,3-dioxygenase (IDO1) is an attractive immunotherapeutic approach for the treatment of a variety of cancers. Dysregulation of this enzyme has also been implicated in other severe diseases such as Alzheimer's disease and arthritis. Small molecule inhibitors of IDO, syntheses, and uses thereof are provided.

Abstract: Inhibition of indoleamine 2,3-dioxygenase (IDO1) is an attractive immunotherapeutic approach for the treatment of a variety of cancers. Dysregulation of this enzyme has also been implicated in other severe diseases such as Alzheimer's disease and arthritis. Small molecule inhibitors of Formula (Ia) and (Ib) of IDO, their synthesis, and uses thereof are provided.

Abstract: Inhibition of indoleamine 2,3-dioxygenase (IDO1) is an attractive immunotherapeutic approach for the treatment of a variety of cancers. Dysregulation of this enzyme has also been implicated in other severe diseases such as Alzheimer's disease and arthritis. Small molecule inhibitors of Formula (Ia) and (Ib) of IDO, their synthesis, and uses thereof are provided.

Abstract: The synthesis and activity of novel LpxA inhibitors is described, these inhibitors present antibacterial activity. The compounds were designed based on a receptor model developed using the crystal structure of LpxA and are arranged to have a favorable binding interaction at the active site of the enzyme. In particular, the compounds present the following formula (I) where V, W, X, Y and Z can be independently C, S, N or O and P1, P2 and P3 are ligands to bind to the three points of the proposed pharmacophore model. They can be chosen from a variety of groups.

Abstract: The present application provides a terpene analogue of Formula (I) or a pharmaceutically acceptable isomer, salt or ester thereof, and methods and uses thereof for treating neurological conditions such as pain in general and neuropathic pain. These terpene analogues can also be used to treat other electrical disorders in the central and peripheral nervous system. Also provided are methods of synthesizing the terpene analogues of Formula I.

Abstract: Therapeutic compounds and methods for modulating amyloid aggregation in a subject, whatever its clinical setting, are described. Amyloid aggregation is modulated by the administration to a subject of an effective amount of a therapeutic compound of the formula or a pharmaceutically acceptable salt or ester, such that modulation of amyloid aggregation occurs. R1 and R2 are each independently a hydrogen atom or a substituted or unsubstituted aliphatic or aryl group. Z and Q are each independently a carbonyl (C?O), thiocarbonyl (C?S), sulfonyl (SO2), or sulfoxide (S?O) group. “k” and “m” are 0 or 1, provided when k is 1, R1 is not a hydrogen atom, and when m is 1, R2 is not a hydrogen atom. In an embodiment, at least one of k or m must equal 1. “p” and “s” are each independently positive integers selected such that the biodistribution of the therapeutic compound for an intended target site is not prevented while maintaining activity of the therapeutic compound.

Abstract: Therapeutic compounds and methods for inhibiting amyloid deposition in a subject, whatever its clinical setting, are described. Amyloid deposition is inhibited by the administration to a subject of an effective amount of a therapeutic compound comprising an anionic group and a carrier molecule, or a pharmaceutically acceptable salt thereof, such that an interaction between an amyloidogenic protein and a basement membrane constituent is inhibited. Preferred anionic groups are sulfonates and sulfates. Preferred carrier molecules include carbohydrates, polymers, peptides, peptide derivatives, aliphatic groups, alicyclic groups, heterocyclic groups, aromatic groups and combinations thereof.

Abstract: The present invention provides for therapies characterized in part by co-administration or combination of antibiotic agents with medicinal compositions comprising as the pro-antibiotic active ingredient either a compound represented by a formula [I] or a pharmaceutically acceptable composite thereof; [wherein X represents oxygen, sulfur, NH, or N-alkyl; R1 and R2 represent hydrogen, tetrazole, or alkyltetrazole, respectively (with the restriction that if R1 is not hydrogen, R2 must be, and vice versa); R3 represents e.g., benzyl, phenyl optionally substituted, biphenyl, napthyl, N-phenylcarboxamido, etc., R4 represents e.g. carboxylic acid, or its alkyl esters, or a bioisoteric equivalent thereof, etc.; R5 represents e.g. hydrogen, carboxylic acid, etc.] in particular, medicine which is useful as therapeutic and/or protective drugs for infectious and/or inflammatory diseases. Other relevant compounds are also provided.

Abstract: The synthesis and activity of novel LpxA inhibitors is described, these inhibitors present antibacterial activity. The compounds were designed based on a receptor model developed using the crystal structure of LpxA and are arranged to have a favorable binding interaction at the active site of the enzyme. In particular, the compounds present the following formula (I) where V, W, X, Y and Z can be independently C, S, N or O and P1, P2 and P3 are ligands to bind to the three points of the proposed pharmacophore model. They can be chosen from a variety of groups.

Abstract: Therapeutic compounds and methods for modulating amyloid aggregation in a subject, whatever its clinical setting, are described. Amyloid aggregation is modulated by the administration to a subject of an effective amount of a therapeutic compound of the formula or a pharmaceutically acceptable salt or ester, such that modulation of amyloid aggregation occurs. R1 and R2 are each independently a hydrogen atom or a substituted or unsubstituted aliphatic or aryl group. Z and Q are each independently a carbonyl (C?O), thiocarbonyl (C?S), sulfonyl (SO2), or sulfoxide (S?O) group. “k” and “m” are 0 or 1, provided when k is 1, R1 is not a hydrogen atom, and when m is 1, R2 is not a hydrogen atom. In an embodiment, at least one of k or m must equal 1. “p” and “s” are each independently positive integers selected such that the biodistribution of the therapeutic compound for an intended target site is not prevented while maintaining activity of the therapeutic compound.

Abstract: Therapeutic compounds and methods for inhibiting amyloid deposition in a subject, whatever its clinical setting, are described. Amyloid deposition is inhibited by the administration to a subject of an effective amount of a therapeutic compound comprising an anionic group and a carrier molecule, or a pharmaceutically acceptable salt thereof, such that an interaction between an amyloidogenic protein and a basement membrane constituent is inhibited. Preferred anionic groups are sulfonates and sulfates. Preferred carrier molecules include carbohydrates, polymers, peptides, peptide derivatives, aliphatic groups, alicyclic groups, heterocyclic groups, aromatic groups and combinations thereof.

Abstract: The present invention relates to compositions which inhibit the binding of nerve growth factor to the p75NTR common neurotrophin receptor and methods of use thereof. In one embodiment, the compound which inhibits binding of nerve growth factor to p75NTR comprises, particularly when bound to nerve growth factor, at least two of the following: (1) a first electronegative atom or functional group positioned to interact with Lys34 of nerve growth factor; (2) a second electronegative atom or functional group positioned to interact with Lys95 of nerve growth factor; (3) a third electronegative atom or functional group positioned to interact with Lys88 of nerve growth factor; (4) a fourth electronegative atom or functional group positioned to interact with Lys32 of nerve growth factor; and (5) a hydrophobic moiety which interacts with the hydrophobic region formed by Ile31, Phe101 and Phe86 of nerve growth factor.

Abstract: Novel compounds that modulate PDE10A, a gene that is primarily expressed in medium spiny neurons of the mammalian striatum and has been found to inhibit striatal output by reducing spiny medium excitability and effect cAMP and cGMP signalling cascades in vivo in rats, and methods for treating psychosis and schizophrenia using the novel compounds. Methods for screening for further compounds to modulate PDE10A activity are also taught.

Abstract: The present invention exploits the discovery that amounts of uracil and thymine metabolites, especially ?-aminoisobutyric acid, in various bodily fluids, especially urine, are correlated with the occurrence of epilepsy when compared to matched control subjects. Analytical and diagnostic protocols, including a novel high performance liquid chromatography system, for use in the invention are disclosed.

Abstract: In certain embodiments, the invention is directed to a method for treating a protein folding disorder comprising administering to a subject a compound of the formulas disclosed. In preferred embodiments, the compounds are bis-indole compounds.

Abstract: Therapeutic compounds and methods for inhibiting amyloid deposition in a subject, whatever its clinical setting, are described. Amyloid deposition is inhibited by the administration to a subject of an effective amount of a therapeutic compound comprising an anionic group and a carrier molecule, or a pharmaceutically acceptable salt thereof, such that an interaction between an amyloidogenic protein and a basement membrane constituent is inhibited. Preferred anionic groups are sulfonates and sulfates. Preferred carrier molecules include carbohydrates, polymers, peptides, peptide derivatives, aliphatic groups, alicyclic groups, heterocyclic groups, aromatic groups and combinations thereof.

Abstract: The present invention relates to compositions which inhibit the binding of nerve growth factor to the p75NTR common neurotrophin receptor and methods of use thereof. In one embodiment, the compound which inhibits binding of nerve growth factor to p75NTR comprises, particularly when bound to nerve growth factor, at least two of the following: (1) a first electronegative atom or functional group positioned to interact with Lys34 of nerve growth factor; (2) a second electronegative atom or functional group positioned to interact with Lys95 of nerve growth factor; (3) a third electronegative atom or functional group positioned to interact with Lys88 of nerve growth factor; (4) a fourth electronegative atom or functional group positioned to interact with Lys32 of nerve growth factor; and (5) a hydrophobic moiety which interacts with the hydrophobic region formed by Ile31, Phe101 and Phe86 of nerve growth factor.

Abstract: Methods and compounds, such as ?-heterocyclic-?-amino acids, useful for the inhibition of epileptogenesis are disclosed. Methods for preparing and using the ?-heterocyclic-?-amino acids of the invention are also described.