University of Michigan

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

Georgetown University

Haiying Sun

Shaomeng Wang

Zaneta Nikolovska-Coleska

Jianfeng Lu

Su Qiu

Yuefeng Peng

Qian Cai

Liang Xin Xu

Chao-Yie Yang

Jianyong Chen

Dongguang Qin

Alan P Kozikowski

Liu Liu

Donna McEachern

Dajun Yang

Zengjian Hu

Naoyuki G Saito

Phillip Dennis

John Brognard

Rong Sheng

Donna Mceachern

Inhibitors of IAP proteins and compositions containing the same are disclosed. Methods of using the IAP protein inhibitors in the treatment of diseases and conditions wherein inhibition of IAP proteins provides a benefit, like cancers, also are disclosed.

Bivalent inhibitors of IAP proteins and therapeutic methods using the same

The invention relates to diazo bicyclic Smac mimetics that are tethered through a covalent linker to give a bivalent species. Bivalent diazo bicyclic Smac mimetics function as inhibitors of Inhibitor of Apoptosis Proteins (IAPs). The invention also relates to the use of bivalent diazo bicyclic Smac mimetics for inducing or sensitizing cells to the induction of apoptotic cell death. Thus, compounds of the invention are useful in the treatment, amelioration, or prevention of hyperproliferative diseases such as cancer.

Bivalent diazo bicyclic Smac mimetics and the uses thereof

The invention relates to diazo bicyclic mimetics of Smac which function as inhibitors of Inhibitor of Apoptosis Proteins. The invention also relates to the use of these mimetics for inducing apoptotic cell death and for sensitizing cells to inducers of apoptosis.

Diazo bicyclic Smac mimetics and the uses thereof

The invention relates to heteroaryl-substituted bicyclic mimetics of Smac which function as inhibitors of Inhibitor of Apoptosis Proteins. The invention also relates to the use of these mimetics for inducing apoptotic cell death and for sensitizing cells to inducers of apoptosis.

Heteroaryl-substituted bicyclic Smac mimetics and the uses thereof

The invention relates to bivalent mimetics of Smac which function as inhibitors of Inhibitor of Apoptosis Proteins. The invention also relates to the use of these mimetics for inducing apoptotic cell death and for sensitizing cells to inducers of apoptosis.

Bivalent SMAC mimetics and the uses thereof

Bivalent Smac mimetics and the uses thereof

The invention relates to conformationally constrained mimetics of Smac which function as inhibitors of Inhibitor of Apoptosis Proteins. The invention also relates to the use of these mimetics for inducing apoptotic cell death and for sensitizing cells to inducers of apoptosis.

Conformationally constrained Smac mimetics and the uses thereof

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

Disclosed are inhibitors of the serine/threonine kinase Akt, pharmaceutical compositions comprising such inhibitors, and a method of preventing or treating a disease or condition in an animal by the use of such inhibitors. The Akt inhibitors have the formula (I) wherein X and Y are independently selected from the group consisting of O, CF, CH, and CHF; wherein A is independently selected from the group consisting of P(O)OH, CH000H, and CH(COOH); Ris selected from the group consisting of H, OH, isosteres of OH, C-Calkyloxy, C-Caryloxy, C-Ccycloalkyloxy, C-Ccycloalkyl C-Calkoxy, C-Calkenyloxy, C-Ccycloalkenyloxy, C-Caralkyloxy, C-Calkylaryloxy, C-Caralkenyloxy, and C-Calkenylaryloxy; R-Rare independently selected from the group consisting of H, OH, isosteres of OH; and Rand Rare independently selected from the group consisting of C-Calkyl, C-Caryl, C-Ccycloalkyl, C-Calkenyl, C-Ccycloalkenyl, C-Caralkyl, C-Calkylaryl, C-Caralkenyl, and C-Calkenylaryl; with the provisos that (i) when X is O, Y is O or CH, and Ris H, at least one of Rand R-Ris not OH; (ii) when A is CHCOOH or CH(COOH), X and Y cannot be simultaneously O; and (iii) all of R-Rare not simultaneously H. The inhibitors can be in the form of a salt also 

Akt inhibitors, pharmaceutical compositions, and uses thereof

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Ann Arbor, MI, United States of America

Haiying Sun