Abstract: Provided are novel heterocyclic sirtuin binding agents, e.g., N-aryl substituted pyridine dicarboxamides, which are useful as sirtuin modulators. Also provided are methods of using the pyridine dicarboxamide compounds for treating sirtuin mediated disorders and conditions, such as diabetes, cancers, and obesity and diseases related to aging.

Abstract: The present invention is directed to novel substituted bicyclic aromatic compounds useful as S-nitrosoglutathione reductase (GSNOR) inhibitors, pharmaceutical compositions comprising such compounds, and methods of making and using the same.

Abstract: Disclosed are methods and compositions for preventing, treating, or ameliorating eosinophilic esophagitis (EoE) in an individual, comprising administering to the individual a therapeutically effective amount of at least one CRTH2 antagonist or a pharmaceutically acceptable salt thereof and at least one proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof. Also disclosed are compositions comprising at least one CRTH2 antagonist or a pharmaceutically acceptable salt thereof and at least one proton pump inhibitor or a pharmaceutically acceptable salt thereof.

Abstract: This invention relates to 2-Aza-bicyclo[2.2.2]octane-3-carboxylic acid (benzyl-cyano-methyl)-amides of formula 1 and their use as inhibitors of Cathepsin C, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of diseases connected with dipeptidyl peptidase I activity, e.g. respiratory diseases.

Abstract: The present disclosure provides methods of increasing proliferation of adult salivary stem cells. The methods include contacting adult salivary stem cells in vivo, in vitro, or ex vivo with an aldehyde dehydrogenase (ALDH) agonist. Increasing proliferation of adult salivary stem cells can be carried out to provide for an increase in the number of adult salivary stem cells in an indi vidual undergoing radiotherapy for head and neck cancer.

Abstract: The present invention belongs to the field of EP1 receptor ligands. More specifically it refers to compounds of general formula (I) having great affinity and selectivity for the EP1 receptor. The invention also refers to the process for their preparation, to their use as medicament for the treatment and/or prophylaxis of diseases or disorders mediated by the EP1 receptor as well as to pharmaceutical compositions comprising them.

Abstract: Compounds of formula (I) or a pharmaceutically acceptable ester, amide, carbamate or salt thereof, including a salt of such an ester, amide or carbamate in which R1 to R9 have meanings as defined in the Specification, are useful as estrogen receptor ligands.

Abstract: The present invention provides compositions and methods for the treatment of a human patient. The methods and compositions of the present invention include composition for the efficient loading of curcumin, comprising: an amount of a curcuminoid:liposome complex effective to load curcumin into the liposome, wherein the curcuminoids has between 2 to 9 weight percent of the total composition and the curcuminoids are natural or synthetic.

Abstract: Disclosed are compounds and pharmaceutical compositions containing compounds that inhibit JMJD2 proteins, including those of the formula (I): wherein R1, R2, R3, R4, and R5 are as defined herein or pharmaceutically acceptable salts thereof. Also disclosed is a method of preventing or treating a viral infection of a host, comprising administering to the host an effective amount of an inhibitor of the JMJD2 family of histone demethylases, for example, a compound of the formula (I). The viral infection may be a primary infection, reactivation of a virus after latency in a host, or may be in a mammal that has undergone, is undergoing, or will undergo immunosuppressive therapy.

Abstract: The present invention relates to a pharmaceutical composition for inhibiting angiogenesis and a novel sulfonyl amide derivative compound which can be useful for the prevention or treatment of angiogenesis-related diseases or disorders. Since the compound used as an active ingredient in the pharmaceutical composition of the invention is specifically bound to UQCRB and inhibits biological functions thereof, apoptosis is not induced and angiogenic responses are inhibited. Therefore, the compound used as an active ingredient in the pharmaceutical composition of the invention can be useful as an effective and safe angiogenesis inhibitory agent.

Abstract: Disclosed are compounds of Formula 1, N-oxides, and salts thereof, wherein Q, A, R1, R2, R3 and n are as defined in the disclosure. Also disclosed are compositions containing the compounds of Formula 1 and methods for treating helminth infections comprising administration to an animal a parasiticidally effective amount of a compound or a composition of the invention.

Abstract: The invention provides a chemical entity of Formula (I) wherein R1, R2, R3, Y, and n have any of the values described herein and compositions comprising such chemical entities; methods of making them; and their use in a wide range of methods, including metabolic and reaction kinetic studies, detection and imaging techniques, and radioactive treatments; and therapies, including inhibiting MAO, and MAO-B selectively, enhancing neuronal plasticity, treating neurological disorders, providing neuroprotection, treating a cognitive impairment associated with a CNS disorder, enhancing the efficiency of cognitive and motor training, providing neurorecovery and neurorehabilitation, enhancing the efficiency of non-human animal training protocols, and treating peripheral disorders (including obesity, diabetes, and cardiometabolic disorders) and their associated co-morbidities.

Abstract: The present invention relates to sodium channel inhibitors of Formula (I): in which R1, R2, R3, R4, R5, X, Y, and Z are as defined herein, and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes. The invention also relates to methods for the preparation of the compounds, and to pharmaceutical compositions containing such compounds.

Abstract: Compounds of formula (I) have antibacterial activity: wherein R represents hydrogen or 1, 2 or 3 optional substituents; W is ?C(R1)—; R1 is hydrogen and R2 is hydrogen, methyl, or fluorine; or R1 and R2 taken together are —CH2—, —CH2CH2, —O—, or, in either orientation, —O—CH2— or —OCH2CH2—; and R3 is a radical of formula -(Alk1)m-(Z)p-(Alk2)n-Q.

Abstract: The invention provides methods of inhibiting the growth or metastasis of cancer in a mammal by inhibiting TopoIIa in the mammal. The invention also provides small molecule inhibitors of TopoIIa useful in the methods of the invention and pharmaceutical compositions containing the therapeutically effective compounds and methods of using the same.

Abstract: The present invention relates to an acrylamide compound of Formula I, or an isomer, pharmaceutically acceptable salt and solvate thereof, to a composition comprising the compound or an isomer, pharmaceutically acceptable salt and solvate thereof, and a pharmaceutically acceptable carrier, excipient or diluent, and to a use of the compound or the composition for prophylaxis and/or treatment of a disease or disorder associated with cardiomyocyte apoptosis.

Abstract: The present invention concerns compounds of general formula (I): Method of preparation and uses thereof.

Abstract: The invention relates to compounds of general formula I wherein R is heteroaryl optionally substituted by R7; or R is heterocycloalkyl or heterocycloalkenyl, optionally substituted by R8; or R is X wherein X is —NR11R12; and pharmaceutically acceptable salts, hydrates, or solvates thereof, for use—alone or in combination with one or more other pharmaceutically active compounds—in therapy, for preventing, treating or ameliorating diseases or conditions responsive to stimulation of neutrophil oxidative burst, responsive to stimulation of keratinocyte IL-8 release or responsive to induction of necrosis.

Abstract: Compounds and methods for treating or preventing a neurodegenerative disease, disorder or condition associated with the overall activity of hsp90 but not with the ATPase activity of hsp90, including peripheral neuropathy, such as peripheral neuropathy caused by chemotherapy or diabetes, disorders 5 of the central nervous system, such as Alzheimer's disease and Parkinsons disease, and motor neuron diseases, such as amyotrophic lateral sclerosis (ALS), in a subject are provided.

Abstract: The invention is directed to Compounds of Formula I: and pharmaceutically acceptable salts or solvates thereof, as well as methods of making and using the compounds.

Abstract: The present invention is directed to a new class of hydroxamic acid derivatives of Formula I, wherein the variables G, T, D, L, A, X, R1 and R2 are as described hereinabove, and their use as LpxC inhibitors, and more specifically their use to treat bacterial infections.

Abstract: [Object] An excellent agent for preventing or treating dementia, schizophrenia, and the like, based on serotonin 5-HT5A receptor modulating action, is provided. [Means for Solution] It was confirmed that acylguanidine derivatives (the following formula I; any one of Z1, Z2, Z3, Z4 and Z5 is nitrogen atom, and the others are carbon atoms) which have the characteristic structure in which the guanidine is bonded to one ring of the quinoline or isoquinoline via a carbonyl group, and a cyclic group is bonded to the other ring, exhibit potent 5-HT5A receptor modulating actions and excellent pharmacological actions based on the 5-HT5A receptor modulating action, and thus can be excellent agents for preventing or treating dementia, schizophrenia, bipolar disorder, or attention deficit hyperactivity disorder. Thus, the present invention has been completed.

Abstract: The present invention provides a novel compound having plasminogen activator inhibitor-1 inhibitory activity, and an inhibitor of PAI-1 comprising the compound as an active ingredient. The present invention also provides a pharmaceutical composition having an inhibitory action on PAI-1 activity and being efficacious in the prevention and treatment of various diseases whose onset is associated with PAI-1 activity.

Abstract: The invention relates to new quinoline derivative compounds of formula (I), to pharmaceutical compositions comprising said compounds, to processes for the preparation of said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.

Abstract: Novel quinoline derivatives are disclosed. Also disclosed are synthesis and use thereof for treating neurodegenerative diseases.

Abstract: Compounds of formula I: wherein R4, R6 and R7 are defined herein, are useful as inhibitors of HIV replication.

Abstract: A method of measuring the effect of an active agent or a stressor on the baseline metabolic indicators of one or more hair follicles, the method including (a) obtaining one or more hair follicles; (b) placing the one or more hair follicles in a vessel, wherein the one or more hair follicles are positioned under one or more sensors; (c) using the one or more sensors to measure the one or more hair follicles' baseline metabolic indicators for both glycolysis and oxidative phosphorylation; (d) exposing the one or more hair follicles to an active agent or a stressor; and (e) using the one or more sensors to measure the one or more hair follicles' respondent metabolic indicators for both glycolysis and oxidative phosphorylation.

Abstract: PAD4 inhibitory compositions and methods for their use in treatment of cancer and autoimmune disease are provided according to embodiments of the present invention.

Abstract: The present invention relates to new biphenyl-3-carboxylic acid modulators of beta-3-adrenoceptor activity, pharmaceutical compositions thereof, and methods of use thereof.

Abstract: Methods of treating a subject having a cardiovascular disease, selecting a therapy for a subject having a cardiovascular disease, identifying a subject having a cardiovascular disease that will benefit or not benefit from exercise therapy, determining whether a subject having a cardiovascular disease should begin, continue, not begin, discontinue, or avoid exercise therapy, determining whether a subject having a cardiovascular disease should continue, discontinue, or avoid exercise therapy, reducing the risk of an adverse outcome (e.g., death) in a subject having a cardiovascular disease, and predicting the efficacy of exercise therapy in a subject having a cardiovascular disease. These methods include determining a level of soluble ST2 in a subject.

Abstract: This invention provides a compound having the structure: wherein R1 is H, halogen, —NR5R6, —NR5—C(?O)—R6, —NH—C(?O)—OR7, —OR7, —NO2, —CN, —SR7, —SO2R7, —CO2R7, CF3, —SOR7, —POR7, —C(?S)R7, —C(?O)—NR5R6, —CH2—C(?O)—NR5R6, —C(?NR5)R6, —P(?O)(OR5)(OR6), —P(OR5)(OR6), —C(?S)R7, C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, aryl, heteroaryl, or heterocyclyl, wherein R5, R6, and R7 and are each, independently, H, C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; m is an integer from 0 to 2; R2 and R3 are each, independently, H, halogen, —NH2, —CX3, —C(?O)OR8, C(?O)R8, —C(?O)NR9R10, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, heteroalkyl, aryl, heteroaryl, or heterocyclyl; wherein X is Cl, Br, or F; R8, R9 and R10 are each, independently, H, C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; Q is —Ar1—Z— or —Z—Ar1—Z—, wherein Ar1 is aryl or heteroaryl; and each occurrence of Z is independently present or

Abstract: The present invention relates to the use of selective insecticidal compositions, characterized by an effective amount of an active compound combination comprising (a) (1) at least one haloalkylnicotinic acid derivative of the formula (I) in which AA and R1A are as defined in the description, or (2) at least one phthalic acid diamide of the formula (II) in which XB, R1B, R2B, R3B, L1B, L2B and L3B are as defined in the description, or (3) at least one anthranilamide of the formula (III) in which A1C, A2C, XC, R1C, R2C, R3C, R4C, R5C, R7C, R8C and R9C are as defined in the description, and (b) at least one crop plant compatibility-improving compound from the group of compounds given in the description, in particular cloquintocet-mexyl, isoxadifen-ethyl and mefenpyr-diethyl for controlling insects and/or arachnids, and a method for controlling insects and/or arachnids using the compositions.

Abstract: The present invention relates to compounds with activity as BACE1 and NF?B modulators, and methods for treating, preventing, or ameliorating neurodegenerative diseases, such as Alzheimer's disease. The present invention is also directed to the treatment of diseases related to dysfunction of cell proliferation, the immune system and/or inflammation using such compounds or pharmaceutical compositions containing such candidate compounds.

Abstract: Treating Sonic Hedgehog-Associated Medulloblastoma comprises inhibiting the synthesis or biologic activity of leukotrienes that drive Nestin expression in cancerous or precancerous granule neuron precursors and that further drive growth and proliferation of medulloblastoma cells through Nestin-mediated aberrant Sonic Hedgehog signaling.

Abstract: In one aspect, the present invention relates to a method of identifying compounds useful in modifying the activity of Aldolase.

Abstract: Patients inflicted with various clustering chronic diseases require treatment with multiple drugs having distinct mechanisms of action. Accordingly, patients with multiple conditions suffer from cumulative side effects of multiple drugs as well as drug-drug interactions. Embodiments, agents, compounds or drugs of the present invention, such as sesquiterpenes, e.g., Zerumbone, replace an equal or larger number of approved drugs during patient treatment. Examples of disorders prevented or ameliorated by administration of the formulations of this invention include but are not limited to inflammatory diseases that may be, oncological, genetic, ischemic, infectious, neurological, hematological, ophthalmological, rheumatoid, orthopedic, neurological, hematological, kidney, vascular, dermatological, gynecological, or obstetric.

Abstract: Diagnostic and therapeutic methods pertaining to diseases and disorders of the breast, uterus and ovary are encompassed herein. More particularly, diagnostic methods for early detection of progenitor cells of breast, uterine, and ovarian cancers are described herein. The identification of markers for these cancer predisposing progenitor cells, which co-express the progesterone receptor (PR) and p63, provides tools and methods of use thereof that facilitate early detection of increased frequency of PR/p63 double positive (PR/p63+) progenitor cells in asymptomatic patients and thus, early detection of increased cancer risk in such patients and assessment, diagnostic stratification, and evaluation of therapeutic intervention in symptomatic patients.

Abstract: Provided is a pharmaceutical composition comprising, as an active ingredient, a quinoline or quinazoline derivative of formula (I), a pharmaceutically acceptable salt, an isomer, a hydrate, and a solvate thereof, which is effective in the prevention and treatment of a cancer, inflammation, autoimmune diseases or neurodegenerative disorders which are induced by the overexpression of inhibitor of apoptosis proteins (IAPs).

Abstract: The present invention relates to the use of avermectin derivative as a drug for the treatment of parasitic infections. The avermectin derivative is represented by the formula (I) wherein: (i) R1 is chosen from the group constituted of —CH(CH3)2, —CH(CH3)CH2CH3, or cyclohexyle, (ii) X represents —CH2CH2—, or —CH?CH—, (iii) R2 is chosen from the group constituted of or —OH group, (iv) R3 is OH or NOH, (v) represents a single bond when R3 is OH, or a double bond when R3 is NOH, as an inhibitor of a membrane-bound protein which transports exogenous compounds out of target cells.

Abstract: In certain embodiments, the disclosure relates to methods of treating or preventing posttraumatic stress disorder comprising administering a pharmaceutical composition comprising effective amount of an angiotensin-converting enzyme inhibitor to a subject in need thereof. In certain embodiments, the angiotensin-converting enzyme inhibitor is administered in combination with an angiotensin receptor blocker.

Abstract: Provided is a method of treating or preventing age-related macular degeneration (AMD) in a patient subject to, or symptomatic of the disease, wherein the method comprises restoring normal lysosomal pH (pHL), or acidifying an abnormally elevated pHL, thus decreasing or preventing a damaging accumulation of lipofuscin or waste products in the retinal pigment epithelium (RPE) cells of the eye of the patient. Further, this method is achieved by modulating the action of the P2X7 and/or P2Y12 receptors of the RPE cells, specifically decreasing the acidity (pHL) of the RPE lysosomes by administering selected receptor antagonists affecting the action of the P2X7 and/or P2Y12 receptors of the RPE. Methods for selecting and quantifying the effectiveness of drugs to restore pHL and determine outer segment clearance rates is also provided using a high through-put screening protocol.

Abstract: The compounds of formula (I) are derived from perhydroquinoline and perhydroisoquinoline and are useful as active pharmaceutical ingredients for the prophylaxis or treatment of diseases caused by 11-beta-hydroxysteroid dehydrogenase type 1 (11-beta-HSD1) enzyme-associated disorders, such as glaucoma, elevated ocular pressure, metabolic disorders, obesity, metabolic syndrome, dyslipidemia, hypertension, diabetes, atherosclerosis, Cushing's syndrome, psoriasis, rheumatoid arthritis, cognitive disorders, Alzheimer's disease or neurodegeneration.

Abstract: To provide novel carboxamides which exhibit an excellent pesticidal activity as pesticides. Carboxamides represented by the following Formula (I) and use thereof as pesticides and an animal parasite control agent: wherein each substituent is as defined in the specification.

Abstract: The present invention provides biaryl oxyacetic acid compounds which may be useful for treating inflammatory disorders, including disorders affecting the respiratory system and skin.

Abstract: The object of the present invention is to find a pharmaceutical composition and a method for treating cancer that show an excellent antitumor effect. Combinational use of 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide and analogues thereof can result in an excellent antitumor effect when combined with a substance having a c-kit kinase-inhibiting activity.

Abstract: The invention relates to compounds of formula (I) wherein the substituents are as defined in the specification, in free form or in the form of a pharmaceutically acceptable salt, solvate, ester, N-oxide thereof; processes for the preparation thereof; to pharmaceuticals containing such compounds, in particular for the use in one or more Protein tyrosine kinase mediated diseases.

Abstract: Compositions comprising extracts or isolated or purified compounds from plants of the genus Corydalis provide prevention and treatment of hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, hepatic steatosis, and metabolic syndrome. Corydalis compounds and their derivatives of natural and synthetic origins lower total cholesterol, LDL-cholesterol, and triglycerides and increase hepatic LDL receptor expression and activate AMP-activated protein kinase. Specific stereoisomers of Corydalis compounds with lipid lowering activity include 14R-(+)-corypalmine, 14R,13S-(+)-corydaline, 14R-(+)-tetrahydropalmatin, (+)-corlumidin, d-(+)-bicuculline, and (+)-egenine.

Abstract: Compounds, pharmaceutical compositions, and methods of using such compounds to treat or prevent diseases or disorders associated with or mediated by JAMM proteins are disclosed. The compounds and compositions inhibit the enzymatic activity of a JAMM domain, including the JAMM domain of the CSN5 subunit of the COP9-signalsome (CSN), the JAMM domain of the Rpn11/Poh1/Psmd14 subunit of the 26S proteasome, the JAMM domain of AMSH, the JAMM domain of AMSH-LP, the JAMM domain of BRCC36, among other JAMM domains.

Abstract: The present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt or ester thereof, wherein R1 to R8, A1 to A3 have the are as described herein and compositions including the compounds.

Abstract: This invention relates to novel quinoline compounds which affect gap junction activity. Also provided are methods of using such compounds and compositions containing the compounds to treat gap junction disorders.