The present invention relates to a peptide and its use as a medicament, in particular in the treatment of metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), cardiovascular disease (CVD) or cholestatic liver disease.

The present invention relates to solid pharmaceutical compositions comprising N-[1-(5-cyano-pyridin-2−ylmethyl)-1H-pyrazol-3-yl]-2-[4-(1-trifluoromethyl-cyclopropyl)-phenyl]-acetamide or pharmaceutically acceptable salt thereof. The invention further relates to methods for manufacturing said compositions and their uses for the treatment or prevention of diseases and disorders linked to T-type calcium channels such as epilepsy.

The present invention is directed to co-therapy and methods for the treatment and prevention of glucose-related disorders such as Type 2 diabetes mellitus and Syndrome X. The present invention is further directed to pharmaceutical compositions for the co-therapy and methods described herein.

The present invention is related to a ribonucleic acid comprising a double stranded structure whereby the double-stranded structure comprises a first strand and a second strand, whereby the first strand comprises a first stretch of contiguous nucleotides and whereby said first stretch is at least partially complementary to a target nucleic acid, and the second strand comprises a second stretch of contiguous nucleotides whereby said second stretch is at least partially identical to a target nucleic acid, and whereby the double stranded structure is blunt ended.

The present invention relates to particularly stable and soluble scFv antibodies and Fab fragments specific for TNF, which comprise specific light chain and heavy chain sequences that are optimized for stability, solubility, in vitro and in vivo binding of TNF, and low immunogenicity. The antibodies are designed for the diagnosis and/or treatment of TNF-mediated disorders. The nucleic acids, vectors and host cells for expression of the recombinant antibodies of the invention, methods for isolating them and the use of the antibodies in medicine are also described.

The present invention provides compounds for inhibiting matriptase 2, or a mutant thereof, and compositions and methods of use thereof.

Compounds described herein may be used for the treatment of neurodegenerative diseases linked to protein misfolding, including prion diseases, Alzheimer's disease, Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), and also other neurodegenerative, degenerative, metabolic and ischemic conditions. Indeed, NAD metabolism impairment is also a critical feature in brain ischemia/reperfusion injury, Wallerian degeneration, kidney failure, multiple sclerosis, aging, and metabolic disorders such as diabetes mellitus. Therapies that elevate or stabilize NAD levels may thus have broad potential for treating many severely debilitating neurological and metabolic conditions. Evidence is provided herein with compounds from 8 lead series for NAD restoring properties and for therapeutic efficacy in cellular and/or animal models of prion disease, PD and ALS.

The invention provides solid forms of 2-((4-((S)-2-(5-chloropyridin-2-yl)-2-methylbenzo[d][1,3]dioxol-4-yl)piperidin-1-yl)methyl)-1-(((S)-oxetan-2-yl)methyl)-1H-benzo[d]imidazole-6-carboxylic acid, 1,3-dihydroxy-2-(hydroxymethyl)propan-2-amine salt for example, a hydrate (e.g. a monohydrate) crystalline form (e.g. Form 2 or Form 3) or an amorphous form; as well as pharmaceutical compositions, and the uses thereof in treating diseases, conditions or disorders modulated by GLP-1R in a mammal, such as a human.

This disclosure is directed, at least in part, to SSTR5 antagonists useful for the treatment of conditions or disorders involving the gut-brain axis. In some embodiments, the SSTR5 antagonists are gut-restricted compounds. In some embodiments, the condition or disorder is a metabolic disorder, such as diabetes, obesity, nonalcoholic steatohepatitis (NASH), or a nutritional disorder such as short bowel syndrome.

The invention provides 2-(substituted phenylhetero) aromatic formate FTO inhibitors, a preparation method thereof, and applications thereof. Specifically, disclosed in the present invention are a 2-(substituted phenylhetero) aromatic formate compound represented by the following formula (I), and a pharmaceutically acceptable salt, a hydrate or a solvate thereof, which can be used as an FTO targeting inhibitor for treating diseases associated with FTO targets, including obesity, metabolic syndrome (MS), type 2 diabetes (T2D), Alzheimer's diseases, and cancers such as breast cancers, small-cell lung cancers, human bone marrow rhabdomyosarcoma, pancreatic cancer, malignant glioblastoma and the like. ##STR00001##