There is a need for new therapeutics that prevent cardiovascular diseases with minimal effects on normal blood clotting. Integrin α2β1 is a good therapeutic target since it can lead to cardiovascular diseases including stroke or myocardial infarction when overexpressed, but does not severely impair normal bleeding when under-expressed.
Integrin α2β1 has been implicated in several other disease states including cancer metastasis, wound healing, viral infections (such as rotaviruses), and glomerular injury. Therefore, novel inhibitors of integrin α2β1 could have potential benefits in preventing cardiovascular disease, as well as in several other therapeutic applications.
Drs. DeGrado and Bennett led the development of novel small molecule inhibitors of integrin α2β1, based on a prolyl-2,3-diaminopropionic acid (DAP) scaffold. These compounds have been shown to inhibit human platelet adhesion and arterial thrombosis in a mouse model with IC50 values in the nanomolar range.
William F. DeGrado, Joel S. Bennett
- Inhibition of integrin α2β1
- IC50 values in nanomolar range
- Cardiovascular diseases
- Cancer metastasis
- Wound healing
- Viral infections
- Glomerular injury
Stage of Development:
Primary human cells and mouse model
Keywords: Integrin, Thrombosis, Hemostasis, Cancer Metastasis, Wound Healing, Viral Infection, Small Molecule
Docket # U4878 and R3789