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 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.
1. A prodrug represented by a formula selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
2. The prodrug of claim 1 , represented by the formula
3. A pharmaceutical composition, comprising a prodrug of claim 1 , or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.
4. A method of treating a disorder in which fibroblast activation protein (FAP) is upregulated, comprising administering to a subject in need thereof a therapeutically effective amount of a prodrug of claim 1 , or a pharmaceutically acceptable salt thereof.
5. The method of claim 4 , wherein the disorder is selected from the group consisting of cancer, fibrosis, and inflammation.
6. The method of claim 4 , wherein the disorder is cancer.
7. The method of claim 4 , wherein the disorder is fibrosis.
8. The method of claim 4 , wherein the disorder is inflammation.