Bach Biosciences, LLC

Tufts College

David George Sanford

William W Bachovchin

Hung-sen Lai

Wengen Wu

Sarah E Poplawski

Hung-Sen Lai

Disclosed are prodrugs of cytotoxic anthracyclines (such as doxorubicin) and other therapeutic agents that are selectively cleaved and activated by fibroblast activating protein (FAP). The prodrugs are useful for targeted delivery of cytotoxic and other agents to FAP-expressing tissues, including cancer (e.g., solid tumors). Also provided are pharmaceutical compounds comprising the prodrugs, as well as methods of using the prodrugs to treat a disorder characterized by FAP upregulation, e.g., cancer, fibrosis, and inflammation.

Fap-activated therapeutic agents, and uses related thereto

FAP-activated therapeutic agents, and uses related thereto

Disclosed are prodrugs of anthracyclines (such as doxorubicin) and derivatives thereof that are selectively cleaved and activated by fibroblast activating protein (FAP). The prodrugs are useful for targeted delivery of 'warhead' anthracycline or anthracycline derivative to FAP-expressing tissues, including cancer (e.g., solid tumors). Also provided are pharmaceutical compounds comprising the prodrugs, as well as methods of using the prodrugs to treat a disorder characterized by FAP upregulation, e.g., cancer undesirable fibrosis and undesirable inflammation.

Disclosed are prodrugs of anthracyclines (such as doxorubicin) and derivatives thereof that are selectively cleaved and activated by fibroblast activating protein (FAP). The prodrugs are useful for targeted delivery of 'warhead' anthracycline or anthracycline derivative to FAP-expressing tissues, including cancer (e.g., solid tumors). Also provided are pharmaceutical compounds comprising the prodrugs, as well as methods of using the prodrugs to treat a disorder characterized by FAP upregulation, e.g., cancer, undesirable fibrosis, and undesirable inflammation.

Disclosed are prodrugs of therapeutic or imaging agents, which prodrugs are selectively cleaved by fibroblast activating protein (FAP) to release the agents. Upon cleavage by FAP of the FAP substrate, the prodrug releases the agent in its active form or in a form that is readily metabolized to its active form. Pharmaceutical compositions comprising the prodrugs, as well as methods of using the prodrugs to treat a disorder characterized by FAP upregulation are also disclosed.

Disclosed are prodrugs of anthracyclines (such as doxorubicin) and derivatives thereof that are selectively cleaved and activated by fibroblast activating protein (FAP). The prodrugs are useful for targeted delivery of 'warhead' anthracycline or anthracycline derivative to FAP-expressing tissues, including cancer (e.g., solid tumors). Also provided are pharmaceutical compositions comprising the prodrugs, as well as methods of using the prodrugs to treat a disorder characterized by FAP upregulation, e.g., cancer, undesirable fibrosis, and undesirable inflammation.

The present invention relates to compositions of peptide and polypeptide analogs that are resistant to proteolysis, pharmaceutical uses thereof, and methods of preparation thereof.

Stable analogs of peptide and polypeptide therapeutics

Polypeptide analogs of the invention that include a) a base amino acid sequence at least 80% identical to one of a GLP-1 fragment; and b) amino acid residues attached to the carboxy terminus of the base amino acid sequence, where the analogs have GLP-1-like activity of longer duration than native GLP-1 and/or the GLP-1 receptor has a greater affinity for the analogs than native GLP-1. Other polypeptide analogs of the invention include a) a base amino acid sequence at least 50% identical to a GLP-1 fragment in which the amino acid residue in the base amino acid sequence corresponding to the P'residue of GLP-1 is an amino acid analog having a tetrasubstituted Ccarbon; and b) amino acid residues attached to the carboxy terminus of the base amino acid sequence, where the analogs have the properties indicated above. The invention also includes methods of treatment where these analogs are administered.

Growing community of inventors

Reading, MA, United States of America

David George Sanford