The Johns Hopkins University

Wukun Liu

Jun O Liu

Wei Shi

Yingjun Li

Ruojing Li

Sarah Head

Jingxin Wang

Zufeng Guo

Manisha Das

Sam Hong

Kalyan Kumar Pasunooti

Hanjing Peng

Jun Liu

Itraconazole, a widely used antifungal drug, has been found to possess potent anti-angiogenic and anti-hedgehog activities, exhibiting promising antitumor activity in several human clinical studies. The wider use of itraconazole in the treatment of cancer, however, has been limited by its potent inhibition of the drug metabolic enzyme CYP3A4 which causes drug-drug interactions. In an effort to eliminate the CYP3A4 inhibition of itraconazole while retaining its anti-angiogenic activity, we synthesized a series of itraconazole derivatives. The newly synthesized analogs of itraconazole were evaluated for their cytotoxicity against human umbilical vein endothelial cells (HUVEC) and their inhibitory activity against CYP3A4 enzyme.

Itraconazole analogs and use thereof

Provided herein are Itraconazole analogs. Also provided herein are methods of inhibition of Hedgehog pathway, vascular endothelial growth factor receptor 2 (VEGFR2) glycosylation, angiogenesis and treatment of disease with Itraconazole analogs.

A Rapafucin library containing compounds of the general structure, (A) and (E), and a synthesis of these compounds are provided. 

Synthesis and composition of rapafucin libraries

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Baltimore, MD, United States of America

Wukun Liu