Abstract: The present invention is directed to novel substituted fused aminopiperidines of structural formula (I) which are inhibitors of the dipeptidyl peptidase-4 enzyme and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-4 enzyme is involved, such as diabetes and particularly Type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-4 enzyme is involved.

Abstract: The present invention is directed to compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.

Abstract: One aspect of the invention generally relates to use of tissue enriched miRNAs as biomarker to estimate tissue damage in a fluid sample. In a second aspect, methods are provided for monitoring a subject who is exposed or might have been exposed to an agent that has a risk of causing tissue injury. In a third aspect, methods are provided for identifying an agent as having a risk of causing tissue injury to a vertebrate subject. In a fourth aspect, kits are provided for practicing the methods of above-listed aspects. The contents of this ABSTRACT are not intended to in anyway limit the scope of the inventions claimed herein.

Abstract: The present invention is directed to pyridyl amide compounds which are antagonists of T-type calcium channels, and which are useful in the treatment or prevention of disorders and diseases in which T-type calcium channels are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which T-type calcium channels are involved.

Abstract: The invention relates to a compound of a formula (I): or a pharmaceutically acceptable salt or ester thereof, useful as a therapeutic agent for various ACC-related disorders.

Abstract: Glucagon receptor antagonist compounds are disclosed. The compounds are useful for treating type 2 diabetes and related conditions. Pharmaceutical compositions and methods of treatment are also included.

Abstract: The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of hepatitis C virus (HCV) gene expression and/or activity. The present invention is also directed to compounds, compositions, and methods relating to traits, diseases and conditions that respond to the modulation of expression and/or activity of genes involved in hepatitis C virus (HCV) gene expression pathways or other cellular processes that mediate the maintenance or development of such traits, diseases and conditions. Specifically, the invention relates to double stranded nucleic acid molecules capable of mediating or that mediate RNA interference (RNAi) against hepatitis C virus (HCV) gene expression, including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules.

Abstract: Compounds having a biphenyl group substituted with a phenyl or heteroaromatic group, as shown in Formula I, including pharmaceutically acceptable salts of the compounds, are CETP inhibitors, and are useful for raising HDL-cholesterol, reducing LDL-cholesterol, and for treating or preventing atherosclerosis:

Abstract: The present invention is directed to 2-aminopyridine compounds which are inhibitors of the beta-secretase enzyme and that are useful in the treatment of diseases in which the beta-secretase enzyme is involved, such as Alzheimer's disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the treatment of such diseases in which the beta-secretase enzyme is involved.

Abstract: Triazole derivatives of structural formula I are selective inhibitors of the 11?-hydroxysteroid dehydrogenase-1. The compounds are useful for the treatment of diabetes, such as noninsulin-dependent diabetes (NIDDM), hyperglycemia, obesity, insulin resistance, dyslipidemia, hyperlipidemia, hypertension, Metabolic Syndrome, and other symptoms associated with NIDDM.

Abstract: This invention relates to compounds, compositions, and methods useful for modulating polycomb group protein EZH2 gene expression using short interfering nucleic acid (siNA) molecules. This invention also relates to compounds, compositions, and methods useful for modulating the expression and activity of other genes involved in pathways of polycomb group protein EZH2 gene expression and/or activity by RNA interference (RNAi) using small nucleic acid molecules. In particular, the instant invention features small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules and methods used to modulate the expression of polycomb group protein EZH2 genes, such as EZH2.

Abstract: This invention relates to compounds, compositions, and methods useful for modulating placental growth factor (e.g., PGF-1 or PlGF-1, PGF-2 or PlGF-2, and/or PGF-3 or PlGF-3) gene expression using short interfering nucleic acid (siNA) molecules. This invention also relates to compounds, compositions, and methods useful for modulating the expression and activity of other genes involved in pathways of placental growth factor gene expression and/or activity by RNA interference (RNAi) using small nucleic acid molecules. In particular, the instant invention features small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules and methods used to modulate the expression of placental growth factor genes.

Abstract: The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of stromal cell-derived factor-1 (SDF-1) gene expression and/or activity. The present invention is also directed to compounds, compositions, and methods relating to traits, diseases and conditions that respond to the modulation of expression and/or activity of genes involved in SDF-1 gene expression pathways or other cellular processes that mediate the maintenance or development of such traits, diseases and conditions. Specifically, the invention relates to small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules capable of mediating or that mediate RNA interference (RNAi) against SDF-1 gene expression.

Abstract: This invention relates to novel methods and formulations of nucleic acid pharmaceutical products, specifically formulations of nucleic acid vaccine products and nucleic acid gene therapy products. The formulations of the disclosure stabilize the conformation of DNA pharmaceutical products.

Abstract: Modified oxyntomodulin derivatives. Such derivatives can be used for the treatment of metabolic diseases such as diabetes and obesity.

Abstract: The present invention is directed to novel substituted aminotetrahydropyrans of structural formula I which are inhibitors of the dipeptidyl peptidase-IV enzyme and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly Type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.

Abstract: This invention relates to compounds, compositions, and methods useful for modulating interleukin and/or interleukin receptor gene expression using short interfering nucleic acid (siNA) molecules. This invention also relates to compounds, compositions, and methods useful for modulating the expression and activity of other genes involved in pathways of interleukin and/or interleukin receptor gene expression and/or activity by RNA interference (RNAi) using small nucleic acid molecules. In particular, the instant invention features small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules and methods used to modulate the expression of interleukin and/or interleukin receptor genes.

Abstract: The present invention relates to compounds and derivatives thereof, their synthesis, and their use as estrogen receptor modulators. The compounds of the instant invention are ligands for estrogen receptors and as such may be useful for treatment or prevention of a variety of conditions related to estrogen functioning including: bone loss, bone fractures, osteoporosis, metastatic bone disease, Paget's disease, periodontal disease, cartilage degeneration, endometriosis, uterine fibroid disease, hot flashes, increased levels of LDL cholesterol, cardiovascular disease, impairment of cognitive functioning, cerebral degenerative disorders, restenosis, gynecomastia, vascular smooth muscle cell proliferation, obesity, incontinence, inflammation, inflammatory bowel disease, sexual dysfunction, hypertension, retinal degeneration and cancer, in particular of the breast, uterus and prostate.

Abstract: Disclosed herein is a novel forward mutation assay based on 5-fluorouracil (5-FU) resistance which utilizes a strain of Salmonella typhimurium derived from the Ames strain TA100. More specifically, the invention provides a high throughput alternative to the standard Ames mutation assay for the evaluation of the genotoxicity activity of compounds during an early stage of the drug development process. The invention also identifies the upp locus as a mutational target that is capable of detecting a diverse spectrum of mutagenic events and further describes a S. typhimurium tester strain, designated FU100 (his+, rfa, ?uvrB, pkM101, 5-fluorouridine resistant) for use in the assay of the invention.

Abstract: The invention disclosed herein describes novel biomarkers useful for risk assessment, screening, prognosis and selection and monitoring of therapy for HDAC mediated cell proliferative disorders. In particular, the invention provides the identities of three particular proteins whose expression patterns are strongly predictive of a particular patient's treatment outcome, e.g., non-responsiveness to SAHA. The expression profile, or pattern, whether embodied in nucleic acid expression, protein expression, or other expression formats will find use in identifying and selecting patients afflicted with a particular HDAC mediated cancer who are likely to be non-responsive to SAHA-based therapy and thus candidates for other treatments.