Cell Signaling Modulation

Enabling Cell Signal Modulation

Enzo’s therapeutic platform provides a basis for the development of pharmaceutical agents that modulate protein-protein interactions. Our scientists and collaborators have unlocked the secrets of a major cell signaling pathway and developed a means to modify biologic activity in several metabolic systems through the use of small molecule drug candidates.

Screening System

We have used metabolic systems to determine the structures of key regulatory proteins and to identify active sites as potential targets for Enzo’s proprietary drug discovery system. Our technology is capable of generating active compounds that range from orally delivered small molecules to peptides and antibodies. We have performed pioneering work on the structure and function of the LDL receptor-related protein “LRP” and its ligands, and we have developed a screening technology to identify active compounds and synthetic proprietary molecules capable of producing biological effects in cell-based systems and animal models. Specifically, our drug discovery platform enables us to:

• generate biological and genetic information concerning LRP;
• determine the structure of LRP-ligand docking sites;
• identify the functionally important residues;
• build a fine structure map of LRP and employ it as the basis for virtual screening;
• establish in vitro biological assays capable of identifying active compounds;
• design and synthesize proprietary molecules that are active in animal models of disease.

Active Drug Candidate Compounds

Through this novel, proprietary functional screening system we have identified small molecules capable of modulating ligand-receptor interactions. Preclinical animal studies have identified lead compounds that:

• indicate a new path for the treatment of osteoporosis and/or osteonecrosis by producing significant increases in total and femoral bone density through new bone formation and significant reduction in alveolar bone loss.
• demonstrate significant glucose lowering activities in standard animal models of diabetes and have the potential to reduce fasting and postprandial glucose levels in these animals.

Other important applications of Enzo’s LRP-centered platform include cancer, skin and hair growth.

Diabetes

Based on our LRP cell signaling modulation technology platform we have identified and are developing a number of active drug candidate compounds that indicate effectiveness for the treatment of type 2 diabetes.

Using genetic animal models and structural and computational biology we have been able to define some of the complex cellular machinery controlling glucose homeostasis, and we have synthesized novel entities that interact at key targets along the biochemical pathway.

Our first-in-class, proprietary orally-active molecules were shown to significantly lower blood glucose in standard animal models of diabetes.

Enzo continues to explore this very exciting line of research and to direct efforts toward the development of these potential therapies with novel mechanisms of action for the treatment of diabetes.

Preclinical Studies for Bone Disorders

Using Enzo’s newest technology platform, LRP cell signaling modulation, we have identified several compounds with potential for treating bone disorders.

One of several candidate drugs, when injected subcutaneously, was shown to induce new bone formation in mouse calvaria, the flat bones that comprise the top of the skull. When delivered orally the compound prevented alveolar bone loss in an endotoxin-induced periodontitis rat model.

These proprietary candidate compounds were identified through an innovative approach that combines structural biology, computational screening, mutational analyses and biological in vitro assays, followed by in vivo animal model systems.

We continue to synthesize and develop these and other novel compounds that show activity in animal models that assess bone density and we are moving them through the drug development continuum.