Georgetown University

University of Michigan

The United States of America, As Represented by the Secretary, Department of Health and Human Services

Jiangsu Ascentage Biomed Development Inc.

Healthquest Pharma Inc.

Dajun Yang

Shaomeng Wang

Liang Xin Xu

Istvan J Enyedy

C Richter King

Terrence R Burke, Jr

Zaneta Nikolovska-Coleska

Yang Gao

Jianyong Chen

Feng-Di Lung

Peter P Roller

Zhu-jun Yao

Alan P Kozikowski

Johannes H Voigt

Liu Liu

Donna McEachern

Chao-Yie Yang

Longchuan Bai

Haiying Sun

Marc E Lippman

Yu Jing

Yunlong Zhou

Ming Guo

Lingling Jiao

Guoping Wang

Guozhi Tang

Yifan Zhai

Jinlin Hou

Xu Qian

Renxiao Wang

Zengjian Hu

Xiaoyong Zhang

Ya-Qui Long

Ya-Qiu Long

Disclosed are a bisdiazabicyclo compound for treating and/or preventing hepatitis virus-related diseases or disorders, a method for treating and/or preventing hepatitis virus-related diseases or disorders by using the bisdiazabicyclo compound, and a use of the bisdiazabicyclo compound in the preparation of a drug for treating and/or preventing hepatitis virus-related diseases or disorders, and/or eliminating or mitigating hepatitis virus-related diseases or disorders.

Bisdiazabicyclo compound for treatment and/or prevention of hepatitis virus-related diseases or disorders

Disclosed herein are certain indoloquinolone compounds, methods of preparation thereof, pharmaceutical compositions thereof, and uses thereof, such as their uses as ALK inhibitors.

Indoloquinolone compounds as anaplastic lymphoma kinase (ALK) inhibitors

The invention relates to small molecules which function as inhibitors of anti-apoptotic Bcl-2 family member proteins (e.g., Bcl-2 and Bcl-xL). The invention also relates to the use of these compounds for inducing apoptotic cell death and sensitizing cells to the induction of apoptotic cell death.

Small molecule inhibitors of anti-apoptotic BCL-2 family members and the uses thereof

The present invention relates to naturally occurring and chemically synthesized small molecule antagonists of Bcl-2 family proteins. In particular, the present invention provides gossypol compounds (e.g., isomers, enantiomers, racemic compounds, metabolites, derivatives, pharmaceutically acceptable salts, in combination with acids or bases, and the like) and methods of using these compounds as antagonists of the anti-apoptotic effects of Bcl-2 family member proteins (e.g., Bcl-2, Bcl-X, and the like). The present invention also provides compositions comprising gossypol compounds and optionally one or more additional therapeutic agents (e.g., anticancer/chemotherapeutic agents). The present invention also provides methods for treating diseases and pathologies (e.g., neoplastic diseases) comprising administering a composition comprising gossypol compounds and optionally one or more additional therapeutic agents (e.g., anticancer/chemotherapeutic agents) and/or techniques (e.g., radiation therapies, surgical interventions, and the like) to a subject or in vitro cells, tissues, and organs.

Small molecule antagonists of Bcl-2 family proteins

The present invention relates to naturally occurring and chemically synthesized small molecule antagonists of XIAP family proteins. In particular, the present invention provides embelin and other XIAP inhibitors and methods of using these compounds as antagonists of the anti-apoptotic effects of XIAP family member proteins. The present invention also provides methods for treating diseases and pathologies (e.g., neoplastic diseases).

Small molecule antagonists of XIAP family proteins

The present invention provides phenylalanine derivatives that inhibit SH2 domain binding with a phosphoprotein. These derivatives include compounds of the formula: W&#x2014;Y-(AA)-Z wherein n is 0 to 15; Y is a phenylalanyl radical having a phenyl ring, an amine end, and a carboxyl end, the phenyl ring having one or more substituents, e.g., hydroxyl, carboxyl, formyl, carboxyalkyl, carboxyalkyloxy, dicarboxyalkyl, dicarboxyalkyloxy, dicarboxyhaloalkyl, dicarboxyhaloalkyloxy, and phosphonoalkyl, or phosphonohaloalkyl; W is a moiety attached to the nitrogen of Y and is, e.g., alkylcarbonyl, oxalyl, alkylaminooxalyl, arylaminooxalyl, arylalkylaminooxalyl, or alkoxyoxalyl; AA is an amino acid, the amine end of which is attached to the carboxyl end of Y; and Z is an arylalkylamino or arylheterocyclyl alkylamino; or a salt thereof; with the proviso that W is not arylalkylamino when the phenyl ring of phenylalanyl contains a phosphonoalkyl or phosphonohaloalkyl substituent at a position para to the alkylamido group and the ortho and meta positions are unsubstituted. The present invention further provides precursors suitable for preparing the phenylalanine derivatives and a method for the preparation of the precursors. The present invention further provides conjugates comprising a precursor and a conjugant that are covalently linked. These conjugates have biological and/or pharmacological properties. 

Phenylanine derivatives

A novel method for erbB-2 kinase inhibition by compounds identifies through computational modeling and data processing and/or rational and de novo drug design is provided the compounds bind erbB-2 kinase molecules and which can be used as erbB-2 kinase agonists or antagonists. These compounds are useful especially in the treatment of cancer, particularly breast cancer, and can be used alone or in combination with other chemotherapeutic agents, particularly with hercetin, a humanized anti-HER-2 antibody, or with radiation therapy. A specific compound which is exemplified is 'compound B17'=methyl-(p-nitrophenyl)-2-propynoate.

ErbB-2 selective small molecule kinase inhibitors

The present invention relates to small molecule antagonists of Bcl-2 family proteins such as Bcl-2 and/or Bcl-X. In particular, the present invention provides non-peptide cell permeable small molecules (e.g., tricyclo-dibenzo-diazocine-dioxides) that bind to a pocket in Bcl-2/Bcl-Xthat block the anti-apoptotic function of these proteins in cancer cells and tumor tissues exhibiting Bcl-2 protein overexpression. In preferred embodiments, the small molecules of the present invention are active at the BH3 binding pocket of Bcl-2 family proteins (e.g., Bcl-2, Bcl-X, and Mcl-1). The compositions and methods of the present invention are useful therapeutics for cancerous diseases either alone or in combination with chemotherapeutic or other drugs.

Small molecule inhibitors targeted at Bcl-2

Redox-stable, non-phosphorylated cyclic peptide inhibitors of SH2 domain binding to target protein, conjugates thereof, compositions and methods of synthesis and use

Disclosed herein are phenylalanine derivative compounds of the following formulaW&#x2014;Y&#x2014;(AA)&#x2014;Zwherein Y is a phenylalanyl radical, AA is an amino acid, n is an integer of 1 to 15, and substituent variables W and Z are as described herein. The compounds can be used to inhibit SH2 binding with phosphoproteins, and to inhibit proliferation of tumor cells.

Phenylalanine derivatives

A compound of formula:in which L is sulfur, sulfoxide, oxygen or methylene, and a compound of formula:in which (i) aais Adi and aais Glu or (ii) each of aaand aais Adi, L is sulfur, sulfoxide, oxygen or methylene, which compounds (and their conjugates) bind to an SH2 domain in a protein comprising an SH2 domain, are non-phosphorylated, are redox-stable in vivo, are characterized by an ICin vivo of less than about 4.0 &#x3bc;M with respect to the SH2 domain in Grb2, and, upon binding to the SH2 domain of Grb2, have a turn conformation. A conjugate comprising a compound as described above and a carrier agent, a composition comprising (i) a compound or a conjugate as described above and (ii) a carrier, a method of inhibiting binding of an SH2 domain in a protein comprising an SH2 domain to a target protein in an animal, wherein the SH2 domain is contacted with a target protein-binding inhibiting effective amount of a compound or a conjugate as described above, and a method of synthesizing such conjugates.

Heregulin antagonists and methods for their use

Growing community of inventors

Rockville, MD, United States of America

Dajun Yang