To effectively treat activin-driven diseases, there is a need for ligand-specific antagonists that minimize the off-target effects of existing soluble receptor-based approaches. Guided by the solution structure of activin, we propose to optimize small molecule antagonists that specifically prevent binding of activin to its receptor. We will then test candidate small molecules using in vitro screening bioassays and in vivo normal and disease models. The specific activin-driven disease that we will tackle is breast cancer and associated cancer-related cachexia. Soluble type II activin receptors have been developed to reverse cachexia, but because the ActRII family binds to multiple ligands, these agents have many off-target effects. Thus, we hypothesize that a small molecule antagonist designed to specifically block the interaction between activin and its receptor will be a more effective candidate drug for treating activin-driven breast cancer and cancer-related cachexia.
|Effective start/end date||9/1/14 → 8/31/16|
- Northwestern Memorial Hospital (Exhibit B.15//9/1/14)
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