Rutgers, the State University of New Jersey

Memorial Sloan Kettering Cancer Center

University of Bonn

The Rockefeller University

Innate Tumor Immunity, Inc.

Abbott Laboratories Corporation

Roger A Jones

Barbara L Gaffney

Thomas Tuschl

Gunther Hartmann

Dinshaw J Patel

Manuel Ascano, Jr

Winfried Barchet

Pu Gao

Thomas Zillinger

Shomir Ghosh

Gary D Glick

Edward James Olhava

William R Roush

Yang Wu

Yizhou Liu

Liang Deng

Weiyi Wang

Joseph E Celebuski

Elizabeth D Veliath

Reza Fathip

Xiaohu Zhang

This disclosure features chemical entities (e.g., a compound that modulates (e.g., agonizes) Stimulator of Interferon Genes (STING), or a pharmaceutically acceptable salt, and/or hydrate, and/or cocrystal, and/or drug combination of the compound) that are useful, e.g., for treating a condition, disease or disorder in which a decrease or increase in STING activity (e.g., a decrease, e.g., a condition, disease or disorder associated with repressed or impaired STING signaling) contributes to the pathology and/or symptoms and/or progression of the condition, disease or disorder (e.g., cancer) in a subject (e.g., a human). This disclosure also features compositions as well as other methods of using and making the same.

Compounds and compositions for treating conditions associated with sting activity

The present disclosure provides, among other things, compounds comprising cyclic dinucleotides containing a 2',5' linkage useful in the design of research tools, as research tools, and as therapeutic modalities such as enzyme modulators.

Compositions and methods for altering second messenger signaling

This disclosure features chemical entities (e.g., a compound that modulates (e.g., agonizes) Stimulator of Interferon Genes (STING), or a pharmaceutically acceptable salt, and/or hydrate, and/or coccrystal, and/or drug combination of the compound) that are useful, e.g., for treating a condition, disease or disorder in which a decrease or increase in STING activity (e.g., a decrease, e.g., a condition, disease or disorder associated with repressed or impaired STING signaling) contributes to the pathology and/or symptoms and/or progression of the condition, disease or disorder (e.g., cancer) in a subject (e.g., a human). This disclosure also features compositions as well as other methods of using and making the same. 

Cyclic dinucleotides for treating conditions associated with STING activity such as cancer

This disclosure features dinucleotide compounds that modulate Stimulator of Interferon Genes (STING) activity, for use for example in the treatment of cancer. This disclosure also features compositions as well as other methods of using and making the same (Formula (A)). A and B are each independently selected from the group consisting of Formulae (i), (ii), (iii), and (iv). 

Cyclic dinucleotides for treating conditions associated with sting activity such as cancer

The invention relates to compositions, methods, kits, and assays related to the use and/or exploitation of isomers of cGAMP as well as the structure of the enzyme cGAS.

The present invention provides STING crystals. The present invention also provides STING modulators that interact with sites present in and/or defined by such crystals. The present invention also provides methods of making and using such crystals and modulators. Other aspects and/or features of the present invention will be apparent to those skilled in the art, reading the present specification.

STING crystals and modulators

The present disclosure provides, among other things, novel cyclic-GMP-AMP (cGAMP) analogs, mimics, mimetics and variants, and compositions and kits thereof; methods of using the compounds as described herein for treating cancer, and immune disease, disorders, or conditions; methods of using the compounds as described herein for modulating cGAS and STING; and methods of designing or characterizing a cGAS modulator.

Provided herein are compounds of formula Ia: and salts thereof. Also provided are pharmaceutical compositions comprising a compound of formula Ia, processes for preparing compounds of formula Ia, intermediates useful for preparing compounds of formula Ia and therapeutic methods using compounds of formula Ia.

Cyclic dinucleosides

The invention provides new biotinylated compounds and methods for their use.

Biotinylated compounds

The invention provides analogs cyclic diguanosine monophosphate (c-di-GMP) having different substituents at the guanine C8 position.

Synthesis and characterization of C8 analogs of c-di-GMP

A universal linker for solid-phase nucleic acid synthesis that is cleaved under conditions orthogonal to those used during the synthesis and deprotection of nucleic acids such as dsDNA or RNA fragments is disclosed. The invention includes compounds of the formula: ##STR1## wherein R.sub.1 is selected from the group consisting of OH, OR.sub.2 and an amino functionalized support and n is an integer ranging from about 1 to about 1000 or more preferably from about 1 to about 100 or greater and R.sub.2 is an alkyl (C.sub.1-20) or greater.

Universal allyl linker for solid-phase nucleic acid synthesis

The following species of N6-activated guanosine derivatives are disclosed:

6-O-substituted guanosine derivatives

Oligonucleotide phosphorylating reagents wherein the silyl moiety has three bulky substituents, such as phenyl or t-butyl, and the silyl moiety is attached to the carbon of an ethanol group whose hydroxyl is an activated phosphate group. The preferred compound is 2-triphenylsilylethyl-2-cyanoethyl-N,N diisopropylaminophosphoramidite. The method of using this reagent to phosphorylate the 5'-OH of nucleosides and oligonucleotides is also disclosed. Nucleosides and nucleotides whose 5'-OH has been phosphorylated by the above reagent are also disclosed. The phosphorylated intermediate bearing the silyl group may be separated from failure product on the basis of bulky substituents on the silyl protecting group, which can be later removed by fluoride ion.

Growing community of inventors

Martinsville, NJ, United States of America

Roger A Jones