Abstract: The present invention provides methods for dilating the bronchi or bronchioles and relaxing a pulmonary smooth muscle in a subject by treating the subject with a pharmaceutical composition, which includes a Histone deacetylase (HDAC) inhibitor. The ability to dilate the bronchi or bronchioles and relax a pulmonary smooth muscle according to the methods of the invention allows treating, alleviating, or inhibiting bronchoconstrictive diseases or disorders and symptoms associated or derived from bronchoconstrictive diseases.

Abstract: Provided are methods for treating MLL-rearranged ALL by administering to a patient an HDAC inhibitor alone or in combination with a DNA demethylating agent. Also provided are methods of treating MLL-rearranged infant ALL. Methods of treating cells by these agents are also provided. Additionally, disclosed is a method for screening for compounds capable to treat MLL-rearranged ALL, in particular, MLL-rearranged infant ALL. In one embodiment, the HDAC inhibitor is romidepsin.

Abstract: Antibacterial compounds of formula I are provided: As well as stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof; pharmaceutical compositions comprising such compounds; methods of treating bacterial infections by the administration of such compounds; and processes for the preparation of the compounds.

Abstract: The present disclosure describes novel standardized citrate replacement fluid solutions and a standardized dialysate solution for use with CRRT methods. The standardized citrate replacement fluid solutions and standardized dialysate solutions do not require modification based on the clinical status of the individual patients. The use of the standardized solutions described herein offers significant advantages over the prior art solutions used in CRRT. The present disclosure describes superior metabolic and electrolyte control and significantly increased dialyzer patency in: (a) 24 intensive care unit (ICU) patients with ARF using a 0.67% trisodium citrate replacement fluid solution, and (b) 32 ICU patients with ARF using a 0.5% trisodium citrate replacement fluid solution. Both groups were treated with Bicarbonate-25 dialysate and achieved effluent rates of 35 mL/kg/hr.

Abstract: Methods of inhibiting cancer cell growth using HDAC10 inhibitors are provided. Methods of treating cancer in a subject using HDAC10 inhibitors are also provided. In certain embodiments, at least one second inhibitor selected from an autophagy inhibitor, an AMPK inhibitor, and methyl pyruvate is also used in the methods. Dose packs comprising HDAC10 inhibitors and at least one second inhibitor are provided. Methods of identifying HDAC10 inhibitors are also provided.

Abstract: The present invention relates to the field of oncology and provides compositions and methods for treating specific cancers, including non small cell lung cancer, breast cancer, thyroid cancer, pancreatic cancer, colon cancer, melanoma, hepatoma and adenocarcinoma. Particularly, compositions and methods involving administration, either simultaneously or sequentially, of pharmaceutical combinations comprising (S)—N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide with other compounds, to patients suffering from cancer are described.

Abstract: The present invention is directed to certain hydroxamate derivatives that are useful in the treatment of hepatitis C. These compounds are also inhibitors of histone deacetylase and are therefore useful in the treatment of diseases associated with histone deacetylase activity. Pharmaceutical compositions and processes for preparing these compounds are also disclosed.

Abstract: This invention relates to new antifungal agents, compositions thereof, and methods for inhibiting the growth of fungi involved in infection and disease of keratinized tissue, such as onychomycosis. The invention also relates to new antifungal agents, compositions thereof, and methods for treating and/or preventing fungal infection and/or disease of keratinized tissue, such as onychomycosis. The invention further relates to a kit comprising said antifungal agent and use of said kit in treatment of fungal infection and/or disease of keratinized tissue, such as onychomycosis.

Abstract: Compounds having the formula wherein the symbols have the meaning described in the specification are hydroxamic acid derivatives of 4-phenyl-4-hydroxy-butyric acid and capable of inhibiting the lethal effects of infection by anthrax bacteria and are useful in the treatment of poisoning by anthrax.

Abstract: Multifunctional compounds are provided, comprising two or more functional moieties selected from: (i) a moiety that imparts an iron chelator function; (ii) a moiety that imparts a neuroprotective function; (iii) a moiety that imparts combined antiapoptotic, neuroprotective and/or neurorestorative functions; (iv) a moiety that imparts brain MAO inhibition, preferably with little or no MAO inhibition in liver and small intestine; (v) a moiety that imparts cholinesterase inhibitory function; and (vi) a moiety that imparts an N-methyl-D-aspartic acid receptor (NMDAR) inhibition, and pharmaceutically acceptable salts and optical isomers thereof. The multifunctional compounds are useful in the treatment or prevention of diseases, disorders or conditions that can be prevented and/or treated by iron chelation therapy, and/or neuroprotection and/or neurorestoration, and/or apoptosis inhibition and/or MAO inhibition and/or cholinesterase inhibition and/or NMADR inhibition.

Abstract: The invention relates to methods and products for enhancing and improving recovery of lost memories. In particular the methods are accomplished through the increase of histone acetylation.

Abstract: Histone deacetylase is a metallo-enzyme with zinc at the active site. Compounds having a zinc-binding moiety, such as, for example, a hydroxamic acid group or a carboxylic acid group, can inhibit histone deacetylase. Histone deacetylase can repress gene expression, including expression of genes related to tumor suppression. Accordingly, inhibition of histone deacetylase can provide an alternate route for treating cancer, hematological disorders, e.g., hemoglobinopathies, and genetic related metabolic disorders, e.g., cystic fibrosis and adrenoleukodystrophy.

Abstract: The present invention encompasses novel triterpene compounds of general formula I, wherein R3a, R3b, R11a, R11b, R31 and R32 are defined as in claim 1, which are suitable for the prevention and/or treatment of diseases mediated by 11 ?-HSD and the use thereof for preparing a medicament having the above-mentioned properties.

Abstract: The present invention provides methods of selectively inducing terminal differentiation, cell growth arrest and/or apoptosis of neoplastic cells, and/or inhibiting histone deacetylase (HDAC) by administration of pharmaceutical compositions comprising potent HDAC inhibitors. The oral bioavailability of the active compounds in the pharmaceutical compositions of the present invention is surprisingly high. Moreover, the pharmaceutical compositions unexpectedly give rise to high, therapeutically effective blood levels of the active compounds over an extended period of time. The present invention further provides a safe, daily dosing regimen of these pharmaceutical compositions, which is easy to follow, and which results in a therapeutically effective amount of the HDAC inhibitors in vivo. The present invention also provides a novel Form I polymorph of SAHA, characterized by a unique X-ray diffraction pattern and Differential Scanning Calorimetry profile, as well a unique crystalline structure.

Abstract: This invention provides compounds of formula (I): wherein R1a, R1b, R1c, R2a, R2b, R2c, and R2d have values as described in the specification, useful as inhibitors of HDAC6. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of proliferative, inflammatory, infectious, neurological or cardiovascular diseases or disorders.

Abstract: This invention provides compounds of formula (I): wherein R1, R1b, R2a, R2b, R2c, and R2d have values as described in the specification, useful as inhibitors of HDAC6. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of proliferative, inflammatory, infectious, neurological or cardiovascular diseases or disorders.

Abstract: There are described compounds having the general formula (I) below and their pharmaceutically acceptable salts thereof, wherein E, X, m, q, R1, R2, n and ZBG have the meanings reported in the description useful, in therapy, as inhibitors of zinc metalloproteinases.

Abstract: The present invention provides a pharmaceutical composition or crystalline composition with a specific dissolution profile, which comprises suberoylanilide hydroxamic acid or a pharmaceutically acceptable salt or hydrate thereof as an active ingredient. The present invention provides a process of producing said crystalline composition or pharmaceutical composition. The present invention also provides compositions with a specific particle size distribution.

Abstract: Disclosed are amino alkyl/aryl hydroxamic acid compounds and pharmaceutical compositions containing such compounds. The disclosed compositions are useful as therapeutics for degenerative diseases in mammal.

Abstract: The present invention concerns the discovery that proteins encoded by a family of genes, termed here HDx-related genes, which are involved in the control of chromatin structure and, thus in transcription and translation. The present invention makes available compositions and methods that can be utilized, for example to control cell proliferation and differentiation in vitro and in vivo.

Abstract: The present invention comprises methods and pharmaceutical compositions for intranasal delivery of effective amounts of DFO directly to the CNS, in particular the brain treatments that inhibit GSK3b in patients with psychiatric disorders including, but not limited to, bipolar disorder, depression, ADHD and schizophrenia. In addition a treatment composition is disclosed which comprises DFO and in certain embodiments combines DFO with one or more of the psychotropic drug types, i.e., antipsychotics, mood stabilizers and antidepressants. Moreover, a treatment for treating impairment of neural plasticity through inhibition of GSK3b is provided as well as prevention of apoptosis of cells through inhibition of GSK3b.

Abstract: The present invention concerns the discovery that proteins encoded by a family of genes, termed here HDx-related genes, which are involved in the control of chromatin structure and, thus in transcription and translation. The present invention makes available compositions and methods that can be utilized, for example to control cell proliferation and differentiation in vitro and in vivo.

Abstract: The present invention is directed to a novel form of suberoylanilide hydroxamic acid and the processes for its preparation.

Abstract: The present application discloses the use of the anti-malarial drug lumefantrine and related compounds in the treatment of cancer.

Abstract: The present invention provides methods of selectively inducing terminal differentiation, cell growth arrest and/or apoptosis of neoplastic cells, and/or inhibiting histone deacetylase (HDAC) by administration of pharmaceutical compositions comprising potent HDAC inhibitors. The oral bioavailability of the active compounds in the pharmaceutical compositions of the present invention is surprisingly high. Moreover, the pharmaceutical compositions unexpectedly give rise to high, therapeutically effective blood levels of the active compounds over an extended period of time. The present invention further provides a safe, daily dosing regimen of these pharmaceutical compositions, which is easy to follow, and which results in a therapeutically effective amount of the HDAC inhibitors in vivo.

Abstract: The present invention is directed in part to methods of preventing or reducing colon carcinogenesis comprising administering to a patient at risk of colorectal cancer, a pharmaceutical preparation comprising disclosed chemopreventive. In another aspect, the invention is directed to methods attenuation of oxygen free radicals comprising administrating to a patient in need thereof an antioxidant effective amount of a compound represented by formula I, IIa or IIb as disclosed herein.

Abstract: The present invention is directed in part to methods of preventing or reducing colon carcinogenesis comprising administering to a patient at risk of colorectal cancer, a pharmaceutical preparation comprising a chemopreventive agent disclosed herein.

Abstract: Histone deacetylase is a metallo-enzyme with zinc at the active site. Compounds having a zinc-binding moiety, such as, for example, a hydroxamic acid group or a carboxylic acid group, can inhibit histone deacetylase. Histone deacetylase inhibition can repress gene expression, including expression of genes related to tumor suppression. Accordingly, inhibition of histone deacetylase can provide an alternate route for treating cancer, hematological disorders, e.g., hemoglobinopathies, genetic disorders, e.g. Huntington's disease and spinal muscular atrophy and genetic related metabolic disorders, e.g., cystic fibrosis and adrenoleukodystrophy.

Abstract: Pharmaceutical compositions including an HDAC inhibitor and a pharmaceutically acceptable carrier wherein the HDAC inhibitor is present in an amount sufficient to achieve a plasma concentration from about 100 nM to about 2 uM and methods of treatment using the same. Pharmaceutical compositions including an HDAC inhibitor and a pharmaceutically acceptable carrier wherein the HDAC inhibitor is present in an amount from 0.1 mg to 100 mg. Pharmaceutical compositions including an HDAC inhibitor and a pharmaceutically acceptable carrier, wherein the concentration of the HDAC inhibitor is sufficient to decrease the relative viability of lymphoblastoid cells by at least about 50 percent and/or is sufficient to decrease the proliferation of lymphoblastoid cells by at least about 60 percent and/or is sufficient to decrease the relative viability of peripheral blood mononuclear cells by less than about 50 percent and methods of treatment using the same.

Abstract: New inhibitors of histone deacetylases having antitumor activity, and the process of preparation thereof are herein described. These compounds belong to the structural formula (I) where R1 is a linear or branched chain containing at least two conjugated double bonds, A is an optionally substituted phenyl or pyridyl ring, Ar is an aryl or heteroaryl group, and R3 is hydrogen or alkoxyalkyl. The application also describes the use of said compounds in the treatment of diseases associated to the deregulation of histone deacetylases activity, such as tumors, as well as the relevant pharmaceutical compositions for administration to patients requiring said treatment.

Abstract: The present invention relates to crystalline forms of the active pharmaceutical ingredient vorinostat, processes for their preparation and their use in pharmaceutical compositions.

Abstract: The present invention relates to an improved process for the preparation of the active pharmaceutical ingredient vorinostat. In particular it relates to a process for preparing vorinostat substantially free from impurities, involving suberic acid, aniline and hydroxylamine as starting materials.

Abstract: The present invention is directed toward a method of treating a subject for a condition mediated by aberrant Wnt/?-catenin signaling by selecting a subject with a condition mediated by aberrant Wnt/?-catenin signaling and administering to the selected subject at least one compound selected from the group consisting of those set forth in Table 1, Table 2, Table 3, and a pharmaceutically acceptable salt thereof. A method of similarly modulating the Wnt/?-catenin pathway in a subject is also discussed.

Abstract: Provided are methods and compositions for the prevention and/or treatment of viral conditions, virally-induced conditions and inflammatory conditions. The methods can comprise administering to a subject a viral inducing agent with an antiviral agent, and optionally an additional agent. The viral inducing agent can be a HDAC inhibitor administered orally.

Abstract: The present invention relates to nucleic acids and polypeptides encoded thereby, whose expression is modulated in brain microvascular endothelial cells undergoing early dynamic inflammation-induced changes in blood-brain barrier functionality. Such polypeptides are referred to as lipopolysaccharide-sensitive (LPSS) polypeptides herein. These nucleic acids and polypeptides may be useful in methods for controlling blood-brain barrier properties in mammals in need of such biological effects. This includes the diagnosis and treatment of disturbances in the blood-brain/retina barrier, brain (including the eye) disorders, as well as peripheral vascular disorders. Additionally, the invention relates to the use of anti-LPSS polypeptide antibodies or ligands as diagnostic probes, as blood-brain barrier targeting agents or as therapeutic agents as well as the use of ligands or modulators of expression, activation or bioactivity of LPSS polypeptides as diagnostic probes, therapeutic agents or drug delivery enhancers.

Abstract: Compounds useful for the treatment of various metabolic disorders, such as insulin resistance syndrome, diabetes, hyperlipidemia, fatty liver disease, cachexia, obesity, atherosclerosis and arteriosclerosis are disclosed.

Abstract: The present invention concerns the discovery that proteins encoded by a family of genes, termed here HDx-related genes, which are involved in the control of chromatin structure and, thus in transcription and translation. The present invention makes available compositions and methods that can be utilized, for example to control cell proliferation and differentiation in vitro and in vivo.

Abstract: The present invention relates to compounds represented by formula (I) or composition comprising at least one of such compounds, which are inhibitors of histone deacetylase. The detailed description of these compounds is disclosed in the Description. These compounds and the composition comprising the same may be useful as medicaments for the treatment of proliferative disorders as well as other diseases involving, relating to or associated with enzymes having histone deacetylase (HDAC) activities.

Abstract: Topical compositions are disclosed that are useful for delivering a therapeutic level of an NSAID to a target within a subject having a local inflammatory disorder. A composition of the present invention comprises a Drug and a solvent system, wherein the solvent system comprises at least two solvent alcohols and wherein the solvent system is present in an amount sufficient to solubilize the Drug, the solvent system is a low alkanol system, and the composition is a single phase composition. Examplary solvent systems are those for which one of the at least two solvent alcohols is polyethylene glycol, glycerin, butylene glycol, diproylene glycol, propylene glycol, ethanol, isopropanol, or a derivative therof. Optionally the local inflammatory disorder is pseudofolliculitis barbae, dermatitis, psoriasis, wounds, or sunburn.

Abstract: This invention provides compounds of formula (I): wherein ring A, X1, X2, X3, R2, R4b, R10, and G have values as described in the specification, useful as inhibitors of HDAC6. The invention also provides pharmaceutical compositions comprising the compounds of the invention, and methods of using the compositions in the treatment of proliferative, inflammatory, infectious, neurological or cardiovascular diseases or disorders.

Abstract: Disclosed are a composition and a method for treating skin disorders, including rosacea, pityriasis rosea, erythema, rhinophyma, and rosacea-associated disorders including pimples, papules, pustules, and telangiectasia.

Abstract: The present invention concerns the discovery that proteins encoded by a family of genes, termed here HDx-related genes, which are involved in the control of chromatin structure and, thus in transcription and translation. The present invention makes available compositions and methods that can be utilized, for example to control cell proliferation and differentiation in vitro and in vivo.

Abstract: The invention relates to methods of inducing smooth muscle relaxation, for example, a method of inducing relaxation of a vascular or a non-vascular muscle or a method of inducing relaxation of the microvasculature, in a subject in need thereof by promoting the accumulation of protoporphyrin IX in the smooth muscle.

Abstract: Antibacterial compounds of formula I are provided: As well as stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof; pharmaceutical compositions comprising such compounds; methods of treating bacterial infections by the administration of such compounds; and processes for the preparation of the compounds.

Abstract: Antibacterial compounds of formula I are provided: As well as stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof; pharmaceutical compositions comprising such compounds; methods of treating bacterial infections by the administration of such compounds; and processes for the preparation of the compounds.

Abstract: Described is a protective solution for avoiding ischemic, storage or ischemia/reperfusion to organs, or to isolated cell systems, or to tissue components after perfusion, surgery, transplantation, or cryopreservation and subsequent reperfusion, which contains alkali ions, and if need be also alkaline earth ions as the electrolyte, a buffer e.g. on a histidine derivation basis, as well as a polyol and/or a saccharide, has an osmolarity of about 290 mosm/l to about 350 mosm/l, as well as a pH value of about 6.8 to about 7.4, and to which hydroxamic acid, and/or one or more hydroxamic acid derivatives are added.

Abstract: It has been discovered that certain natural mRNAs serve as metabolite-sensitive genetic switches wherein the RNA directly binds a small organic molecule. This binding process changes the conformation of the mRNA, which causes a change in gene expression by a variety of different mechanisms. Modified versions of these natural “riboswitches” (created by using various nucleic acid engineering strategies) can be employed as designer genetic switches that are controlled by specific effector compounds. Such effector compounds that activate a riboswitch are referred to herein as trigger molecules. The natural switches are targets for antibiotics and other small molecule therapies.

Abstract: A pest control agent containing a compound represented by the following Formula (1), wherein A represents a carbon atom, a nitrogen atom, or the like, K represents a non-metal atom group necessary for forming a cyclic linking group derived from a 5- or 6-membered aromatic ring, in combination with A and two carbon atoms to which A bonds, X represents a hydrogen atom, a halogen atom, or the like, n represents an integer of from 0 to 4, T represents —C(=G1)-Q1 (wherein G1 and G2 represent an oxygen atom or the like, Q1 represents a phenyl group which may have a substituent, a heterocyclic group which may have a substituent, or the like), or the like, Q2 represents a phenyl group or the like, G3 represents an oxygen atom or the like, and R1 and R2 each independently represent a hydrogen atom, a C1-C6 alkyl group, or a group represented by -L-D, or the like (provided that at least either R1 or R2 represents a group represented by -L-D); as an active ingredient exhibits an excellent effect.

Abstract: The present application is directed to a method of treating diseases of the central nervous system (CNS) comprising administering to a individual in need of treatment a therapeutically effective amount of an inhibitor of histone deacetylase. In particular embodiments, the CNS disease is a neurodegenerative disease. In further embodiments, the neurogenerative disease is an inherited neurodegenerative disease, such as those inherited neurodegenerative diseases which are polyglutamine expansion diseases. The individual can be a mammal such as a primate or human.

Abstract: The present invention provides compounds that are inducers or inhibitors of apoptosis of apoptosis preceded by cell-cycle arrest. In addition, the present invention provides pharmaceutical compositions and methods for treating mammals with leukemia or other forms of cancer or for treating disease conditions caused by apoptosis of cells.