Angiogenesis preclinical studies

While the role of PHD inhibitors in the treatment of anemia is now validated, therapeutic validation is less certain in other HIF-associated pathologies such as wound healing, ulcerative colitis, therapeutic angiogenesis, and treatment of acute ischemic events such as myocardial ischemia and stroke. All of these indications are supported by a compelling array of in vitro and in vivo preclinical studies but their utility in the clinical setting remains to be evaluated and represents exciting possibilities for the future of small-molecule inhibitors of PHD enzymes. 

Antithrombotic prophylactic in Europe, for interstitial cystitis in the United States Animal models to treat osteoarthritis, preclinical studies as anticancer agent, inhibits metastasis and angiogenesis 1, 32-37... 

Antiangiogenic activity as a heparanase inhibitor, HCII-mediated anticoagulant Preclinical studies inhibitor of tumor metastasis, tumor growth, and angiogenesis 38, 39... 

A myriad of preclinical and first-in-man clinical studies suggest that cell therapy has a positive effect on cardiac and vascular repair. In fact, in most studies, the tested cell types were found to be effective, even in the absence of the evidence of robust cell engraftment. This unexpected outcome defines how little we actually understand at present about the underlying mechanism ) of cell-mediated repair, We attribute much repair to direct participation of the transplanted cells in angiogenesis or myogenesis, but in truth, despite promising clinical outcomes, relatively little clinical data exist to support this contention. 

Three other LNA-based compounds are at preclinical development studies. ENZ3042 is a specific inhibitor of survivin, which plays a vital regulatory role in both apoptosis and cell division. Survivin is overexpressed heavily in many cancers and in newly formed endothelial cells engaged in angiogenesis but almost absent in normal adult differentiated tissue. Clinically, survivin expression is associated with poor prognosis, increased cancer recurrence, and resistance to therapy. The compound therefore has the potential to improve the response to therapy in a wide variety of malignant solid tumors. 

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