The J. David Gladstone Institutes

University of California

Ithaca College

Buck Institute for Research on Aging

Mount Sinai School of Medicine

Deutsches Krebsforschungszentrum

Napa Therapeutics Limited

Eric M Verdin

Scott Michael Ulrich

John Newman

Melanie Ott

Brian J North

Wolfgang Fischle

Franck O Dequiedt

Albert Jordan

Bjoern Schwer

Robert A Volkmann

Warner C Greene

Ming-Ming Zhou

Li Gan

Xu Chen

Aneel K Aggarwal

Min Xie

Vincent Castronovo

Steven E Kauder

Manfred Jung

Alexander P Doerr

Hye-Sook Kwon

Lin-feng Chen

Rosalba Perrone

Steve Felstead

Vincenzo Calvanese

Hyungwook Lim

Frederick R Nelson

Margaret Jackson

Elena Silva

David Waltregny

Jotham W Coe

Disclosed are heteroaryl amide inhibitors of CD38 and methods of making and using the same in disease and disorder treatment.

Heteroaryl amide inhibitors of CD38

In various embodiments a compound comprising the enantiomerically enriched S-isomer S-BHB-S-1,3-butanediol is provided along with methods of use thereof.

S-enantiomers of beta-hydroxybutyrate and butanediol and methods for using same

Aspects of the present disclosure include fatty acid &#x3b2;-hydroxyester compounds (e.g., fatty acid esters of &#x3b2;-hydroxybutyrate), fatty acid esters of butanediol, and pharmaceutically acceptable salts thereof. Also provided are pharmaceutical compositions having one or more fatty acid &#x3b2;-hydroxyester compounds and/or one or more fatty acid esters of butanediol. Methods for treating a subject by administering one or more esters to the subject are also provided. Kits containing one or more of the subject esters are also described.

Medium chain fatty acid esters of beta-hydroxybutyrate and butanediol and compositions and methods for using same

Medium chain fatty acid esters of &#x3b2;-hydroxybutyrate and butanediol and compositions and methods for using same

The present disclosure provides for recombinant nucleic acids, and cells and virions comprising the recombinant nucleic acids, that can be used to identify, isolate, and/or purify cells latently infected with immunodeficiency virus. A subject recombinant nucleic acid includes (a) a first nucleotide sequence encoding a first reporter polypeptide that produces a first detectable signal, where the first nucleotide sequence is operably linked to an immunodeficiency virus promoter and is translated as an early gene; and (b) a second nucleotide sequence encoding a second reporter polypeptide that produces a second detectable signal that is distinguishable from the first detectable signal, where the second nucleotide sequence is operably linked to a non-immunodeficiency virus promoter. In some aspects, the first and second nucleotide sequences are both positioned between a shared 5' long terminal repeat (LTR) and a shared 3&#x2032; LTR. Also provided are related methods.

Dual-color HIV reporter system for the detection of latently-infected cells

The present disclosure provides methods of reducing the level of acetylated Tau in a neuron or a glial cell in an individual, the methods involving administering to the individual a prodrug that is converted in the individual to salicylate. The present disclosure provides methods of treating a tauopathy in an individual, the methods involving administering to the individual a prodrug that is converted in the individual to salicylate.

Methods for treating tauopathy

The present disclosure provides methods and compositions for reactivating latent immunodeficiency virus in an immunodeficiency virus-infected cell. The methods generally involve contacting an immunodeficiency virus-infected cell with a synergistically effective amount of an inhibitor of cytosine methylation and an NF-&#x3ba;B activator. The present disclosure provides methods and compositions for reducing the reservoir of latent immunodeficiency virus in an individual, and for treating an immunodeficiency virus infection in an individual.

Methods for the reactivation of latent HIV using cytosine methylation inhibitors and NF-KB activators

The present disclosure provides a method of increasing an immune response in an individual, the method involving administering to an individual in need thereof an inhibitor of SIRT1. The present disclosure provides a method of reducing an immune response, e.g., to treat chronic immune hyperactivity, the method generally involving administering to an individual in need thereof an activator of SIRT1. The present disclosure provides a method of modulating activation and differentiation of CD4T cells.

Use of SIRT1 activators or inhibitors to modulate an immune response

This invention discloses the first cellular acetylated substrate protein of SIRT3, Acetyl-CoA synthetase 2 (AceCS2), which is a mitochondrial matrix protein. AceCS2 is reversibly acetylated at lysine 642 (Lys642) in the active site of the enzyme. The mitochondrial sirtuin SIRT3 interacts with AceCS2 and deacetylates Lys642 both in vitro and in vivo. Deacetylation of AceCS2 by SIRT3 activates the acetyl-CoA synthetase activity of AceCS2. Thus, a mammalian sirtuin directly controls the activity of a metabolic enzyme via reversible lysine acetylation. Modulators of the acetylation status or the activity of AceCS2 are useful for the treatment of pathological conditions, such as type II diabetes, hypercholesterolemia, hyperlipidemia, and obesity.

Regulation of protein activity by reversible acetylation

The present invention provides methods of detecting cells showing smooth muscle differentiation. The present invention further provides methods of detecting tumor cells. The present invention further provides compositions and methods for treating smooth muscle cell disorders.

Methods of treating smooth muscle cell disorders

The present invention provides methods for identifying agents that modulate a level or an activity of tubulin deacetylase polypeptide, as well as agents identified by the methods. The invention further provides methods of modulating tubulin deacetylase activity in a cell. The invention further provides methods of modulating cellular proliferation by modulating the activity of tubulin deacetylase.

Methods of modulating tubulin deacetylast activity

The present invention provides nucleic acid molecules that encode histone deacetylase, as well as recombinant vectors and host cells that include the subject nucleic acid molecules. Also provided are histone deacetylase polypeptide compositions. The histone deacteylase nucleic acid molecules are useful in a variety of diagnostic and therapeutic applications, which are also provided.

Histone deacetylase and methods of use thereof

The present invention provides the structural determination of a bromodomain determined by NMR spectroscopy. The present invention also provides binding partners for the bromodomain. The present invention further provides the structural determination of the Tat-P/CAF binding complex determined by NMR spectroscopy. In addition, the present invention provides methodology for related drug discovery using high throughput drug screening or structure based rational drug design using the three-dimensional data.

ZA loops of bromodomains

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San Francisco, CA, United States of America

Eric M Verdin