Abstract: Provided is a method of treating or preventing a cardiomyopathy associated with activation of at least one kinase in the MAP kinase signaling pathway in heart tissue by providing to a subject an inhibitor of at least one kinase in the ERK signaling pathway or in the JNK signaling pathway, or both. In some embodiments, the cardiomyopathy is associated with one or more mutations in the LMNA gene, which encodes A-type nuclear lamins, or in the EMD gene, which encodes an inner nuclear membrane protein.

Abstract: The present invention provides a compound of formula (I) said compound is inhibitor of MMP-12 and/or MMP-13, and thus can be employed for the treatment of a disorder or disease characterized by abnormal activity of MMP-12 and/or MMP-13. Accordingly, the compound of formula (I) can be used in treatment of disorders or diseases mediated by MMP-12 and/or MMP-13. Finally, the present invention also provides pharmaceutical composition that include the compound of formula (I).

Abstract: The invention provides methods for treatment of acute coronary syndrome and prediction of adverse cardiac events on the basis of elevations of catalytic iron in biological fluid of a human subject. An embodiment of the invention provides a method for early detection of acute coronary syndrome (ACS) in a human subject at the time of presentation of the chest pain. The method includes analyzing a test sample of the biological fluid for amount of catalytic iron and detecting acute coronary syndrome in the human subject.

Abstract: This invention pertains to certain active carbamic acid compounds which inhibit HDAC activity and which have the following formula: wherein: A is a C5-20heteroaryl or C5-20carboaryl group and is optionally substituted; Q1 is a C2-7alkylene group having a backbone of at least 2 carbon atoms, and is optionally substituted; J is —N(R1)C(?O)— or —C(?O)N(R1)—; R1 is hydrogen, C1-7alkyl, C3-20heterocyclyl, or C5-20aryl; and, Q2 is C1-7alkylene, C5-20arylene, C5-20arylene-C1-7alkylene, or C1-7alkylene-C5-20arylene having a backbone of at least 3 carbon atoms, and is optionally substituted; and pharmaceutically acceptable salts thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit HDAC, and, e.g., to treat proliferative conditions, such as cancer and psoriasis.

Abstract: The invention relates to histone deacetylase (HDAC) inhibitors to treat proliferative diseases. The present invention provides novel class III histone deacetylase inhibitors, in particular SIRT1 inhibitors, to reverse the silencing of hypermethylated genes, in combination with one or more other agents, in proliferative diseases such as cancer. The present invention provides methods of activating genes that are silenced by methylation in a subject by administering a HDAC inhibitor in combination with one or more agents.

Abstract: Disclosed herein are methods and compositions for diagnosing and treating diseases associated with a loss of cystatin E/M expression including cervical intraepithelial neoplasia and cervical cancer. Genetic mutations and exonic deletions which result in a loss of cystatin E/M expression are also disclosed.

Abstract: The invention relates to a method of determining whether a human subject is suffering from or at risk for developing pancreatic cancer by determining the methylation level of an ID4 gene promoter or the expression level of an ID4 gene in a biological sample from a human subject. Also disclosed are a method of analyzing the methylation level of an ID4 gene promoter or the expression level of an ID4 gene in a pancreatic cancer cell, and a method of inhibiting the methylation of an ID4 gene promoter or enhancing the expression of an ID4 gene by contacting a pancreatic cancer cell with a compound that decreases the methylation level of an ID4 gene promoter or increases the expression level of an ID4 gene in the cell.

Abstract: Compounds can be used to act as inhibitors of enzymes having histone deacetylase activity for the medical therapy of conditions which predispose a person for the development of a disease, such as but not limited to cancer, inflammatory or metabolic diseases. Such conditions are linked to genetically inherited mutations of crucial genes which predispose a person with this condition to develop the disease phenotype. Thus, such compounds can be used for a suppressive therapeutic approach—the SUPPRESSION THERAPY—in order to inhibit or delay the onset or progression of the genetically predisposed disorder. Furthermore, a clinically used medicament can be manufactured for the SUPPRESSION THERAPY of such inherited predisposing conditions.

Abstract: Zn2+-chelating motif-tethered fatty acids as histone deacetylase (HDAC) inhibitors. Compounds performed well in in vitro and in vivo tests.

Abstract: Embodiments herein relate to the field of lysosomal storage disorders, and, more specifically, to methods of treating lysosomal storage disorders such as Niemann-Pick type C disease, for instance with inhibitors of histone deacetylases, particularly inhibitors of class 1 histone deacetylases. In various embodiments, methods of treating Niemann-Pick type C disease with inhibitors of class 1 histone deacetylases are described.

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 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: Compounds having the formula wherein the symbols have the meaning described in the specification are hydroxamic acid derivatives of phenoxy-acetic acids and analogs capable of inhibiting the lethal effects of infection by anthrax bacteria and are useful in the treatment of poisoning by anthrax.

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 invention relates to pharmaceutical preparations and methods for treating individuals infected with the human immunodeficiency virus (HIV). The pharmaceutical preparations comprise SAHA and another anti-viral agent. The invention also relates to methods for treating HIV infected patients, particularly patients with persistent, latent HIV infection of CD4+ T cells, and thus make it possible to not just suppress but to eradicate the HIV infection.

Abstract: The onset ratios and pathological conditions of collagen-induced arthritis and adjuvant arthritis in model mice and rats, respectively, were successfully ameliorated by topically expressing the cyclin-dependent kinase inhibitors p161nk4a and p21Cip1 in articular tissues using adenoviral vectors. In the synovial cells of CDKI-transduced mice, expression of inflammatory cytokines was inhibited. Described are the use of the p21Cip1 protein for inhibiting abnormal proliferation of synovial tissues, inflammation in synovial tissues and/or expression of inflammatory cytokines in synovial tissues; the p21Cip1 gene; compounds promoting the activity or expression of the p21Cip1 protein; and pharmaceutical compositions containing these molecules. Also provided are method of screening for compounds participating in the abnormal proliferation of synovial tissues, inflammation in synovial tissues and/or the expression of inflammatory cytokines in synovial tissues targeting the p21Clip1 protein.

Abstract: The invention relates to compositions and methods of treatment using an iron chelator, an antioxidant, estrogen, and/or combinations thereof, optionally, linked to a nanoparticle, to treat a subject in need thereof. The compositions and methods may be used to restore or protect the normal functions of osteoblast and osteoclast by depleting iron and inhibiting oxidative damage. The compositions and methods may also be used to increase the bone formation rate in a subject.

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: The invention is based on the discovery of a novel neuroprotective peptide. In addition, the invention rests on the discovery that the NAP peptide enhances the association of tau and the brain-specific beta tubulin subunit. In addition, NAP modifies microtubule assembly and dynamics, in part, by affecting the tyrosination of microtubule proteins. The invention provides compositions and methods for treatment and prevention of neuronal disorders, including NAP-binding and tau-binding agents, tau peptide mimetics, NAP-like and NAP-like tau peptide mimetics.

Abstract: Described herein are derivatives of arylsulfonamido-substituted hydroxamic acid of formula (I) having good solubility in water and inhibitory activity of matrix metalloproteinases, useful for the preparation of pharmaceutical compositions for the treatment of diseases associated to a pathologic activity and/or an over-expression of metalloproteinases, and of cosmetic preparations having anti-ageing properties in particular for hair and skin.

Abstract: The present invention pertains to the general field of chemical synthesis, and more particularly to methods for the synthesis of certain hydroxamic acid compounds, and in particular, (E)-N-hydroxy-3-(3-phenylsulfamoyl-phenyl)-acrylamide, also known as PXD101 and Belinostat®, comprising, for example, the steps of: (SAF) sulfonamide formation; (PURC) optional purification; (AAA) alkenyl-acid addition, comprising: either (i): the steps of, in order: (ACAEA) alkenyl-carboxylic acid ester addition; (PURE) optional purification; and (CAD) carboxylic acid deprotection; or (ii): the step of: (ACAA) alkenyl-carboxylic acid addition; (PURF) optional purification; (HAF) hydroxamic acid formation; and (PURG) optional purification.

Abstract: The present invention is directed to compositions which contain a combination of at least one histone deacetylase inhibitor (HDAC inhibitor) and a retinoid. The composition is in particular a cosmetic preparation. It was found that the combination of an HDAC inhibitor and retinol or a derivative thereof is in particular useful for treating wrinkles but also for thickening the epidermis and for improving hair growth.

Abstract: A solid, implantable dosage form comprising a therapeutically active agent in solid form, optionally with one or more pharmaceutically acceptable excipients, wherein the one or more excipients, when present, do not lead to a significant delay or prolongation of the release of active agent, as compared to an equivalent dosage form containing no excipients when tested in vitro.

Abstract: The present invention relates to desferoxamine conjugates, derivatives and analogues thereof. In particular, the present invention relates to desferoxamine conjugates, analogues and derivatives thereof, and methods for reducing levels of metals, especially iron, in a mammal. Uses of the compounds according to the invention are also provided. Compounds of the present invention may also be used to treat iron dyshomeostasis disorders, cancer, malaria and fungal infections. The compounds of the invention may be formulated into a pharmaceutical composition or packaged into kits.

Abstract: The invention relates to a compound represented by the following formula (I): and pharmaceutically acceptable salts, stereoisomers, enantiomers, prodrugs and solvates thereof. The compounds are useful as an agent for enhancing the neurite outgrowth and preventing or treating of diseases associated with HDAC in particular, tumor or cell proliferative diseases. In particular, the compounds of the invention can be used as an agent for anti-cancer, anti-diabetic, and anti-neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, Spinocerebellar Ataxias (SCA), and human spinal muscular atrophy (SMA).

Abstract: Some embodiments of the invention comprise systems, methods and/or compositions for the systemic use of histone deacetylase inhibitors (“HDACi”) to protect against or alleviate the effects of radiation exposure, whether due to hostile actions, such as terrorist activity; through therapeutic radiation exposure; or through other methods of intentional or unintentional exposure to radiation, including but not limited to, total body irradiation.

Abstract: This invention pertains to certain active carbamic acid compounds which inhibit HDAC activity and which have the formula (1) wherein: A is an aryl group; Q1 is an aryl leader group having a backbone of at least 2 carbon atoms; J is an amide linkage selected from: —NR1C(?O)— and —C(?O)NR1—; R1 is an amido substituent; and, Q2 is an acid leader group; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit HDAC, and, e.g.

Abstract: The treatment and prevention of neurodegenerative diseases by repression of the transcriptional complex that silences the promoter of the UCHL1 gene.

Abstract: The present invention describes therapeutic compositions comprising one or more minerals, including trivalent iron, divalent manganese and salts thereof, suitable in facilitating synthesis and deposition of connective tissue matrix, particularly rich of elastin and collagen, and mitogenic potential in human dermal fibroblasts. It also describes the phenomenon in which stimulation of elastogenesis by arterial SMC associates with a net decrease in proliferation of these cell types. The present invention also describes methods of treatment of human skin fibroblasts and arterial smooth muscle cells. The therapeutic compositions of the present invention comprise one or more of trivalent iron or divalent manganese or salts thereof and may be combined with an elastic tissue digest.

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: A coordination complex having a physiologically acceptable pKa includes a metal and a biologically active agent. The pKa of the coordination complex is less than the pKa of the biologically active agent. A pharmaceutical solution for treating a patient includes a coordination complex and water, wherein the coordination complex is at least partially soluble in the water at physiological pH and in a therapeutically efficacious concentration. A method for treating a patient includes administering a pharmaceutical solution including a coordination complex and water to a patient in need of a biologically active agent.

Abstract: The present invention provides new compositions and methods for treatment of intracellular parasites. The compositions comprise one or more hydroxamic acids in an amount sufficient to interfere with the activity of one or more histone deacetylases in the intracellular parasites. The compositions and methods can be used to treat members of the Apicomplexa group of intracellular parasites.

Abstract: Due to the poor long-term clinical outcome in the adult patients with several forms of acute leukemia novel treatment strategies are needed to overcome resistance and sensitize the leukemia blasts to the extrinsic and intrinsic pathway of apoptosis. Treatment with LAQ824 and Apo-2L/TRAIL alone has been recognized to induce apoptosis of leukemia blasts but intrinsic mechanisms of resistance limit the antileukemia activity of either agent when administered alone. The inventive method overcomes the resistance to current apoptosis inducing treatments demonstrated by AML and CML-BC cells by concomitantly administering Apo-2L/TRAIL with the histone deacetylase inhibitor LAQ824.

Abstract: Disclosed are compositions and methods for skincare, e.g., reducing skin wrinkles and for treating skin disorders.

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: 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 such compounds.

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: 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: The invention relates to a combination of treatments, more particularly a combination treatment for HIV-1 infection. The present invention is directed to the use of bryostatin-1 and their natural and synthetic derivatives for AIDS therapy, in particular to the use of bryostatins in combination with other active drugs such as Histone Deacetylases (HDACs) inhibitors and anti-retrovirals, for the treatment of HIV-1 latency. According to the present invention, we provide a combination therapy for the treatment of HIV-1 latency which employs bryostatin-1 (and analogues) and one of the following HDAC inhibitors; valproic acid, butyrate derivatives, hydroxamic acids and benzamides. While HDACi can be used in continuous dosing protocol, bryostatins can be used following a cyclical dosing protocol. Bryostatins can be formulated in pharmaceutical acceptable carriers including nanoparticles, phospholipids nanosomes and/or biodegradable polymer nanospheres.

Abstract: The invention provides processes and compositions for enhancing the immunogenicity of TAP-1 expression-deficient cells by increasing the presentation of MHC Class I surface molecules for detection by cytotoxic T-lymphocyte cells through increased TAP-1 expression, which comprises administering to the TAP-1 expression-deficient cells a TAP-1 expression increasing amount of a bio-acceptable substance that promotes transcription of TAP-1 gene in the cells to cause enhanced MHC Class I surface expression of the cells. The bio-acceptable substance may be a histone H3 deacetylase inhibitor, such as trichostatin A, a transcriptional co-activator having intrinsic histone acetyl transferase activity or a histone acetyl transferase comprising at least one member of the CBP/p300 protein family. The process and compositions increase the immunogenicity of the target cells to enhance their destruction by cytotoxic lymphocytes.

Abstract: Topical alcoholic gel compositions are disclosed that are useful for delivering therapeutic levels of an NSAID to target in and below the skin. The compositions comprise a topically active drug, an alcoholic solvent, a polymeric thickener, and optionally a keratolytic agent. In one embodiment, excellent viscosity for dermal application is attained without the need of a step for neutralizing the pH of the composition. Alcoholic and alcohol-free topical compositions comprising an NSAID prodrug are also disclosed. The compositions are particularly useful for the treatment of pseudofolliculitis barbae.

Abstract: The present invention provides methods and compositions for modulating HDAC4 activity and modulating the activity of proteins downstream of HDAC4 in the muscle transcriptional pathway in a cell by modulating HDAC4 activity. Further provided are methods and compositions for treating muscle atrophy and/or inflammation by inhibiting HDAC4 activity.

Abstract: The present invention relates to a method for treating a subject having or at risk of a diabetes-related disorder. In a preferred embodiment, the method involves increasing the level or activity of Hypoxia Induced Factor 1 (HIF-1 ?) in pancreatic-?-cells or insulin-sensitive tissues in the subject by administering to the subject an inhibitor of a protein that decreases the level or activity of HIF-1?. The present invention also relates to a method of transplanting pancreatic islet cells in a subject.

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 relates generally to a method of treating a neoplastic condition and to agents useful for same. More particularly, the present invention is directed to a method of facilitating the treatment of a metastatic neoplastic tumour in a localised manner by effecting the exposure of neoplastic cell intra-cellular molecules, preferably intra-nuclear molecules, suitable for use as a therapeutic target. The co-localisation of tumour cells and metastases to discrete tissue locations thereby renders the method of the present invention useful in terms of the delivery of bystander-based therapy.

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: Biphenyl and phenyl-naphthyl compounds bearing a hydroxamic group, which are endowed with antitumor, and anti-angiogenic activity These compounds are therefore particularly useful for the treatment of drug-resistant tumors.

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: The invention refers to the use of a cytokine antagonist which modulates the expression and/or the function of a cytokine, particularly a Th2 helper cell cytokine, in a cell and causes the down-regulation of anti-apoptotic proteins in said cell through the cytokine modulation for sensitizing cells for apoptosis. In particular, the cells that can be treated with the cytokine antagonists are drug-resistant cancer cells which fail to undergo apoptosis.

Abstract: The present invention provides methods of treating an RNA viral infection, generally involving administering an agent that reduces the activity of a host cell protein required for maturation of a viral protein, where the emergence of variant virus resistant to the agent is reduced. The present invention further provides combination therapies for viral infection, involving administration of two or more agents that reduce the activity of a host cell protein required for maturation of a viral protein.