Discovery of Indenopyrazoles as a New Class of Hypoxia Inducible Factor (HIF)-1 Inhibitors.
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Minegishi H, Fukashiro S, Ban HS, Nakamura H
Discovery of Indenopyrazoles as a New Class of Hypoxia Inducible Factor (HIF)-1 Inhibitors.
ACS Med Chem Lett. 2013 Jan 27;4(2):297-301. doi: 10.1021/ml3004632. eCollection 2013 Feb 14.
- PubMed ID
- 24900662 [ View in PubMed]
- Abstract
The indenopyrazole framework was investigated as a new class of HIF-1alpha inhibitors. Indenopyrazole 2l was found to most strongly inhibit the hypoxia-induced HIF-1alpha transcriptional activity (IC50 = 0.014 muM) among all of the known compounds having relatively simple structures, unlike manassantins. Indenopyrazole 2l suppressed HIF-1alpha transcriptional activity without affecting both HIF-1alpha protein accumulation and HIF-1alpha/HIF-1beta heterodimerization in nuclei under the hypoxic conditions, suggesting that 2l probably affected the transcriptional pathway induced by the HIF-1alpha/HIF-1beta heterodimer.