Cytovia, Inc.

Han-Zhong Zhang

Sui Xiong Cai

John A Drewe

Shailaja Kasibhatla

Jared Kuemmerle

John F W Keana

Nilantha Sudath Sirisoma

Eckard Weber

Hong Zhang

P Sanjeeva Reddy

William E Kemnitzer

Ben Y Tseng

Kristin P Ollis

Songchun Jiang

Yan Wang

Katayoun Jessen

Federico Gaeta

Wu Yang

Nicole Marion English

Serguei Maliartchouk

Sungchun Jiang

Disclosed are 3-aryl-6-aryl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles and related compounds thereof, represented by the Formula I: wherein Ar, Ar, and X are defined herein. The present invention relates to the discovery that compounds having Formula I are activators of caspases and inducers of apoptosis. Therefore, the activators of caspases and inducers of apoptosis of this invention may be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

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The present invention is directed to novel derivatives of gambogic acid and analogs thereof. The present invention also relates to the discovery that novel derivatives of gambogic acid are activators of caspases and inducers of apoptosis. Therefore, the activators of caspases and inducers of apoptosis of this invention can be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

Derivatives of gambogic acid and analogs as activators of caspases and inducers of apoptosis

The present invention relates to screening methods useful for drug discovery of apoptosis inducing compounds. In particular, the screening methodology relates to using Apoptosis Inducing Proteins (AIPs) as a target for the discovery of apoptosis activators useful as anticancer agents. The screening methods of the present invention can employ homogenous or heterogeneous binding assays using purified or partially purified AIPs; or whole cell assays using cells with altered levels of one or more AIPs. The invention also contemplates use of gambogic acid or GA-related compounds which bind AIPs and can accordingly be used to raise antibodies useful for drug discovery. Alternatively, labeled GA is used for competitive binding assays for drug discovery. Such assays afford high throughput screening of chemical libraries for apoptosis activators.

Methods of treating diseases responsive to induction of apoptosis and screening assays

Disclosed are protease inhibitors for coronaviruses and SARS-CoV, or picornaviruses, and the use of these protease inhibitors for preventing, reducing, ameliorating and treating a disease or condition caused by coronaviruses and SARS-CoV, or picornaviruses. Also disclosed are methods of reducing or preventing the spread of coronavirus, or picornaviruses, and preventing or reducing the replication of coronavirus, or picornaviruses, with the compounds of the present invention.

Protease inhibitors for coronaviruses and SARS-CoV and the use thereof

The present invention is directed to substituted 3-aryl-5-aryl-[1,2,4]-oxadiazoles and analogs thereof, represented by the Formula I: wherein Ar, Ar, A, B and D are defined herein. The present invention also relates to the discovery that compounds having Formula I are activators of caspases and inducers of apoptosis. Therefore, the activators of caspases and inducers of apoptosis of this invention may be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

Method of using substituted 3-aryl-5-aryl-[1,2,4]-oxadiazoles and analogs as activators of caspases and inducers of apoptosis and the use thereof

Disclosed are 3,5-disubstituted-[1,2,4]-oxadiazoles and analogs thereof, represented by the Formula I: wherein Ar, R, A, B and D are defined herein. The present invention relates to the discovery that compounds having Formula I are activators of caspases and inducers of apoptosis. Therefore, the activators of caspases and inducers of apoptosis of this invention may be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

3,5-disubstituted-[1,2,4]-oxadiazoles and analogs as activators of caspases and inducers of apoptosis and the use thereof

The present invention relates to novel fluorescent dyes, novel fluorogenic and fluorescent reporter molecules and new enzyme assay processes that can be used to detect the activity of caspases and other enzymes involved in apoptosis in whole cells, cell lines and tissue samples derived from any living organism or organ. The reporter molecules and assay processes can be used in drug screening procedures to identify compounds which act as inhibitors or inducers of the caspase cascade in whole cells or tissues. The reagents and assays described herein are also useful for determining the chemosensitivity of human cancer cells to treatment with chemotherapeutic drugs. The present invention also relates to novel fluorogenic and fluorescent reporter molecules and new enzyme assay processes that can be used to detect the activity of type 2 methionine aminopeptidase, dipeptidyl peptidase IV, calpain, aminopeptidase, HIV protease, adenovirus protease, HSV-1 protease, HCMV protease and HCV protease.

Fluorogenic or fluorescent reporter molecules and their applications for whole-cell fluorescence screening assays for caspases and other enzymes and the use thereof

The present invention is directed to derivatives of gambogic acid and analogs thereof. Exemplary gambogic acid derivatives of the present invention include, among others, derivatives substituted in the C10 and C28 positions of gambogic acid. The present invention also relates to the discovery that certain preferred compounds of the present invention are activators of caspases and inducers of apoptosis. Therefore, the activators of caspases and inducers of apoptosis of this invention can be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

3,5-Disubstituted-[1,2,4]-oxadiazoles and analogs as activators of caspases and inducers of apoptosis and the use thereof

The present invention is directed to substituted 1-benzoyl-3-cyano-pyrrolo[1,2-&#x3b1;]quinolines and analogs thereof, represented by the general Formula I: wherein R&#x2013;R, L, Q, dash line and Ar are defined herein. The present invention also relates to the discovery that compounds having Formula I are activators of caspases and inducers of apoptosis. Therefore, the activators of caspases and inducers of apoptosis of this invention can be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

Substituted 1-benzoyl-3-cyano-pyrrolo [1,2-a] quinolines and analogs as activators of caspases and inducers of apoptosis

The present invention is directed to substituted N'-(arylcarbonyl)-benzhydrazides, N&#x2032;-(arylcarbonyl)-benzylidene-hydrazides and analogs thereof, represented by the Formulae I and II: wherein Ar, Ar, and R&#x2013;Rare defined herein. The present invention also relates to the discovery that compounds having Formulae I and II are activators of caspases and inducers of apoptosis. Therefore, the activators of caspases and inducers of apoptosis of this invention may be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

Substituted N'-(arylcarbonyl)-benzhydrazides, N&#x2032;-(arylcarbonyl)-benzylidene-hydrazides and analogs as activators of caspases and inducers of apoptosis and the use thereof

The present invention is directed to substituted 3-aryl-5-aryl-[1,2,4]-oxadiazoles and analogs thereof, represented by the Formula I:wherein Ar, Ar, A, B and D are defined herein. The present invention also relates to the discovery that compounds having Formula I are activators of caspases and inducers of apoptosis. Therefore, the activators of caspases and inducers of apoptosis of this invention may be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

Substituted 3-aryl-5-aryl-[1,2,4]-oxadiazoles and analogs as activators of caspases and inducers of apoptosis and the use thereof

The present invention relates to novel fluorescent dyes, novel fluorogenic and fluorescent reporter molecules and new enzyme assay processes that can be used to detect the activity of caspases and other enzymes involved in apoptosis in whole cells, cell lines and tissue samples derived from any living organism or organ. The reporter molecules and assay processes can be used in drug screening procedures to identify compounds which act as inhibitors or inducers of the caspase cascade in whole cells or tissues. The reagents and assays described herein are also useful for determining the chemosensitivity of human cancer cells to treatment with chemotherapeutic drugs. The present invention also relates to novel fluorogenic and fluorescent reporter molecules and new enzyme assay processes that can be used to detect the activity of type 2 methionine aminopeptidase, HIV protease, adenovirus protease, HSV-1 protease, HCMV protease and HCV protease.

Fluorescence dyes and their applications for whole-cell fluorescence screening assays for caspases, peptidases, proteases and other enzymes and the use thereof

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San Diego, CA, United States of America

Han-Zhong Zhang