Recently, the paper “Discovery of Novel Aryl Carboxamide Derivatives as Hypoxia-Inducible Factor 1α Signaling Inhibitors with Potent Activities of Anticancer Metastasis” was published in the internationally renowned academic journal Journal of Medicinal Chemistry, with the associate professor Liu Mingming from School of Pharmacy of Anhui Medical University (AHMU) as the first author, professor Liu Xinhua of AHMU and Professor Wang Yang of Fudan University as the co-corresponding authors (DOI: 10.1021 / acs.jmedchem.9b01313).
In this study, the researchers adopted the technique of fragment-based lead discovery to identify a thiazole carboxamide fragment of HIF-1 inhibitors, then conducted systematic activation-oriented structural modification and optimization, and discovered the most active HIF-1 inhibitor pyridine carbonamide Cpd-30m (IC50 = 0.32 μM). Preliminary mechanism research showed that the compound attenuated hypoxia-induced HIF-1α accumulation, inhibited migration and invasion of tumor cells as well as angiogenesis, and blocked breast cancer lung metastasis in the mice model, which generated new ideas for the research and development of new anti-metastasis drugs.
Journal of Medicinal Chemistry, the journal of American Chemical Society, is known as the top academic journal in the field of medicinal chemistry. This is the second time for the scholars from School of Pharmacy to publish an academic paper in this journal since April 2019, thus indicating the achievements of the medicinal chemistry team of School of Pharmacy in the design and synthesis of lead compounds.
Link to the paper: https://pubs.acs.org/doi/10.1021/acs.jmedchem.9b01313