This invention provides amine-linked C.sup.3-glutarimide Degronimers and Degrons for therapeutic applications as described further herein, and methods of use and compositions thereof as well as methods for their preparation.

This invention provides Degronimers that have carbon-linked E3 Ubiquitin Ligase targeting moieties (Degrons), which can be linked to a targeting ligand for a protein that has been selected for in vivo degradation, and methods of use and compositions thereof as well as methods for their preparation.

This invention provides Degronimers that have carbon-linked E3 Ubiquitin Ligase targeting moieties (Degrons), which can be linked to a targeting ligand for a protein that has been selected for in vivo degradation, and methods of use and compositions thereof as well as methods for their preparation.

A method of synthesizing a clopidogrel metabolite is provided. A piperidone intermediate is formed from a mandelate. An asymmetric ketone reduction of the piperidone intermediate is performed. A mercapto installation is performed on the piperidone intermediate to form a clopidogrel metabolite that includes a 4-carbon chiral center having an (R) configuration.

A method of synthesizing a clopidogrel metabolite is provided. A piperidone intermediate is formed from a mandelate. An asymmetric ketone reduction of the piperidone intermediate is performed. A mercapto installation is performed on the piperidone intermediate to form a clopidogrel metabolite that includes a 4-carbon chiral center having an (R) configuration.

A method of synthesizing a clopidogrel metabolite is provided. A piperidone intermediate is formed from a mandelate. An asymmetric ketone reduction of the piperidone intermediate is performed. A mercapto installation is performed on the piperidone intermediate to form a clopidogrel metabolite that includes a 4-carbon chiral center having an (R) configuration.

A method of synthesizing a clopidogrel metabolite is provided. A piperidone intermediate is formed from a mandelate. An asymmetric ketone reduction of the piperidone intermediate is performed. A mercapto installation is performed on the piperidone intermediate to form a clopidogrel metabolite that includes a 4-carbon chiral center having an (R) configuration.

Methods and compositions for drug discovery, analysis and treatment of a proliferative disorder characterized by abnormal cells in a mammalian subject are provided according to aspects of the present invention which include administering a pharmaceutically effective amount of a combination of: a cytotoxic agent, a SET agonist and a SET ribosome antagonist. Methods and compositions according aspect of the present invention incorporate agents effective to regulate and/or affect selective translation in a cell characterized by abnormal proliferation, such as a cancer cell, thereby promoting death of the cell.

Methods and compositions for drug discovery, analysis and treatment of a proliferative disorder characterized by abnormal cells in a mammalian subject are provided according to aspects of the present invention which include administering a pharmaceutically effective amount of a combination of: a cytotoxic agent, a SET agonist and a SET ribosome antagonist. Methods and compositions according aspect of the present invention incorporate agents effective to regulate and/or affect selective translation in a cell characterized by abnormal proliferation, such as a cancer cell, thereby promoting death of the cell.

The present invention is directed to a combination therapy involving a type II anti-CD20 antibody and a selective Bcl-2 inhibitor for the treatment of a patient suffering from cancer, particularly, a CD20-expressing cancer.