Compositions, methods and kits for treating active or passive titin-induced cardiac muscle stiffness by administering an HDAC6 specific inhibitor or an HDAC6 activator.

Compositions, methods and kits for treating active or passive titin-induced cardiac muscle stiffness by administering an HDAC6 specific inhibitor or an HDAC6 activator.

The present invention relates to pharmaceutical compositions comprising fixed dose combinations of a DPP-4 inhibitor drug and/or a SGLT-2 inhibitor drug, and metformin XR, processes for the preparation thereof, and their use to treat certain diseases.

In some embodiments, the invention is directed to a method for diagnosing fibrosis and/or fibrosis related diseases and to a method for screening a pharmaceutically active compound for the treatment of fibrosis and/or fibrosis related diseases. The present invention further relates to compositions for use in the treatment, amelioration, and/or prevention of fibrosis. In certain embodiments, the compositions modulate the activity of a miRNA for the treatment, amelioration, and/or prevention of fibrosis. In certain embodiments, the compositions inhibit the activity of miR-21 for the treatment, amelioration, and/or prevention of fibrosis.

The present invention is directed to a compound of Formula (I) or a pharmaceutically acceptable salt thereof. Compounds of Formula (I) are CD38 inhibitors, which can be used to treat a disease or condition in a subject that benefits from an increase in NAD.sup.+ or to treat a mitochondrial disorder in a subject. Such disease or condition is a muscle structure disorder, a neuronal activation disorder, a muscle fatigue disorder, a muscle mass disorder, a metabolic disease, a cancer, a vascular disease, an ocular vascular disease, a muscular eye disease, or a renal disease. The present description discloses the synthesis and characterisation of exemplary compounds as well as pharmacological data thereof (e.g. pages 30 to 135; examples 1 to 61; table). Such an exemplary compound is e.g. N-((1r,4r)-4-(2-methoxyethoxy) cyclohexyl)-5-(thiazol-5-yl)-1H-indole-7-carboxamide (II).

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Methods for preventing or treating diastolic dysfunction in an individual comprising administering to an individual in need of said prevention or treatment a therapeutically effective amount of a mGluR5 negative allosteric modulator, compositions comprising a mGluR5 negative allosteric modulator for use in treatment of diastolic dysfunction and pharmaceutical compositions comprising same.

Methods for preventing or treating diastolic dysfunction in an individual comprising administering to an individual in need of said prevention or treatment a therapeutically effective amount of a (gamma) γ-secretase modulator or inhibitor, compositions comprising a (gamma) γ-secretase modulator or inhibitor for use in treatment of diastolic dysfunction and pharmaceutical compositions comprising same.

The present invention provides a compound having a PDHK inhibitory activity and useful for the treatment or prophylaxis of diabetes (type 1 diabetes, type 2 diabetes etc.), insulin resistance syndrome, metabolic syndrome, hyperglycemia, hyperlactacidemia, diabetic complications (diabetic neuropathy, diabetic retinopathy, diabetic nephropathy, cataract etc.), cardiac failure (acute cardiac failure, chronic cardiac failure), cardiomyopathy, myocardial ischemia, myocardial infarction, angina pectoris, dyslipidemia, atherosclerosis, peripheral artery disease, intermittent claudication, chronic obstructive pulmonary disease s, brain ischemia, cerebral apoplexy, mitochondrial disease, mitochondrial encephalomyopathy, cancer, pulmonary hypertension, Alzheimer disease, vascular dementia, glaucoma, diabetic retinopathy, retinopathy of prematurity, retinal vein occlusion, ischemic optic neuropathy or chronic kidney disease. The present invention relates to a compound of the formula [I-a], or a pharmaceutically acceptable salt thereof:

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wherein each symbol is as defined in the DESCRIPTION.

The present invention is directed to a method for treating diabetes. The method comprises administering to a subject in need thereof dapansutrile, or a pharmaceutically acceptable solvate thereof, in an effective amount. Oral administration is a preferred route of administration.

This disclosure provides, inter alia, systems and methods for testing products for ammonia oxidizing bacteria, quality control, and providing products with ammonia oxidizing bacteria. The systems and methods herein may be used, inter alia, to treat diseases associated with low nitrite levels, skin diseases, and diseases caused by pathogenic bacteria.