Development of anti-angiogenic tyrosine kinases inhibitors: molecular structures and binding modes

Cancer Chemotherapy and Pharmacology
Jingya ZhangGuisen Zhao

Abstract

Since the hypothesis that solid tumors cause angiogenesis by secreting pro-angiogenic factors was introduced, research on angiogenesis has proceeded continuously. Development of inhibitors targeting the angiogenic tyrosine kinases, to block downstream signal transduction pathways, has become an important approach to cancer therapy. Our goal was to study the development and mechanism of anti-angiogenic tyrosine kinases inhibitors. We researched data on discovery of the inhibitors and their binding modes using the PubMed, Web of Science, Food and Drug Administration (FDA), and Clinical Trials Web sites. In the last decade, many small molecule inhibitors targeting angiogenesis have been designed and synthesized with many now entering the clinic or gaining FDA approval. Advances in understanding regulatory mechanisms of angiogenesis have enabled development of these drugs. The development of inhibitors up to Phase 3 clinical trials and, for many, FDA approval has helped leading to the discovery of additional compounds. The structures, activities, and binding modes of these inhibitors are discussed in this review. Though the angiogenesis inhibitors have different chemical structures, they share similar binding modes. Their interacti...Continue Reading

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