The instant invention provides workflows for the design and characterization of mechanism-based sirtuin modulating compounds, including new or improved sirtuin activating compounds. Workflows for the design of mechanism-based sirtuin activating compounds are provided, based on conditions that must be satisfied by activators if they are to exploit the common catalytic mechanism of all sirtuin enzymes and hence increase catalytic efficiency for any sirtuin and any substrate.

Methods for detecting abdominal aortic aneurysm (AAA) or predisposition to AAA in a apoE subject, methods for monitoring the efficacy of treatment of AAA in a subject, and methods for evaluating the severity of AAA or risk of AAA in a subject involve measuring the amount of tetrahydrobiopterin (H4B) present in the test sample and comparing it to the amount of H4B present in a standard or previous test sample. A decreased amount of H4B present in the test sample compared to the standard is indicative of AAA or predisposition to AAA. Treatment can be administered to the subject prior to a second time point, and an increased amount of H4B present in the second test sample compared to the first test sample is indicative of effective treatment of AAA. Candidates can be identified for further testing or monitoring for AAA, and/or for treatment for AAA.

The present invention provides compounds and methods for assaying redox state of metabolically active cells and methods for assaying enzyme activity and/or metabolite level by coupling to redox defining co-factor NAD(P)/NAD(P)H measurement.

The invention relates to a genetically encoded fluorescent sensor for nicotinamide adenine dinucleotide, as well as methods of preparation and uses thereof. In one aspect, this invention relates to a sensor for detecting nicotinamide adenine dinucleotide, particularly, a recombinant fluorescent fusion protein sensor for detecting nicotinamide adenine dinucleotide. In one specific aspect, this invention relates to a recombinant fluorescent fusion protein sensor for detecting reduced nicotinamide adenine dinucleotide (NADH); in another specific aspect, this invention relates to a recombinant fluorescent fusion protein sensor for detecting oxidized nicotinamide adenine dinucleotide (NAD.sup.+); in yet another aspect, the invention relates to a recombinant fluorescent fusion protein sensor for detecting the ratio of reduced to oxidized nicotinamide adenine dinucleotide. This invention also relates to the method of preparing the sensors, and uses of the sensors in detecting NADH, NAD.sup.+, NADH/NAD.sup.+ ratio, screening drugs and measuring NADH metabolism.

The invention relates to the in vitro and in cellulo detection of the cofactors nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). Provided is a sensor molecule for fluorescence or luminescence-based detection of a nicotinamide adenine dinucleotide analyte, in particular for detecting the concentrations of NAD+, NADP and/or the ratios of the concentrations of NAD/NAD H and NADP/NADPH, the sensor comprising (i) a binding protein (BP) for the nicotinamide adenine dinucleotide analyte, the BP being derived from sepiapterin reductase (SPR; EC 1.1.1.153) (ii) a SPR ligand (SPR-L) capable of intramolecular binding to said BP in the presence of the oxidized form of said analyte; and (iii) at least one fluorophore.

The present invention relates to an in vitro method for detecting cAMP or cGMP comprising a) contacting a mixture with a complex of a tracer and a dequencher, wherein the tracer is a fluorophore covalently linked to a cAMP quencher, and b) measuring the change in fluorescence. Furthermore, the present invention relates to the use of said method for determining the cAMP or cGMP concentration in the mixture, for determining the activity of a receptor wherein the signal transduction of the receptor comprises cAMP or cGMP and for screening of a ligand for such a receptor.

Methods and formulations for treating onocological disorders in humans using Coenzyme Q10 are described.

Disclosed herein are ATP biosensor fusion proteins and their use for assaying ATP levels in cells.

A modified luciferase protein which is a sensor for molecules including cAMP is provided. The modified luciferase protein includes one or more heterologous amino acid sequences, at least one of which directly or indirectly interacts with cAMP.

Antibodies (e.g., sdAbs) binding to PCSK9 are described. Nucleic acids encoding such Abs, host cells expressing such Abs and pharmaceutical composition comprising same are described. The use of these PCSK9-binding Abs for lowering low-density lipoprotein-cholesterol (LDL-C) levels and for the treatment of cardiovascular disorders, is also described.