The Pursuit of Transformational Medicines
The DiMarchi laboratory has made contributions to advance discovery and development of specific drugs, such as Humulin®, Humatrope®, rGlucagon®, Humalog®, Evista® and Forteo®. The primary focus of current research is the integration of macromolecules and conventional small molecules to achieve transformational pharmacology. Glucagon, Glucagon-like Peptide-1 (GLP-1), and Glucose-dependent Insulinotropic Polypeptide (GIP) are regulatory hormones responsible for maintaining control of metabolism, most notably glucose homeostasis. A series of novel peptides which exhibit high potency and balanced activity across these three receptors have demonstrated superior, sustained efficacy in lowering body weight and glucose in animal models. These pre-clinical results established the basis for several ongoing human studies with specific mixed agonists. Additionally, a set of peptide-estrogen conjugates possessing full GLP-1 agonism with linker chemistries that enable differential estrogen release consistently proved to be more efficacious and safer in lowering body weight than the comparable controls.