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Discovery of Indenopyrazoles as a New Class of Hypoxia Inducible Factor (HIF)-1 Inhibitors.

ABSTRACT: The indenopyrazole framework was investigated as a new class of HIF-1? inhibitors. Indenopyrazole 2l was found to most strongly inhibit the hypoxia-induced HIF-1? transcriptional activity (IC50 = 0.014 ?M) among all of the known compounds having relatively simple structures, unlike manassantins. Indenopyrazole 2l suppressed HIF-1? transcriptional activity without affecting both HIF-1? protein accumulation and HIF-1?/HIF-1? heterodimerization in nuclei under the hypoxic conditions, suggesting that 2l probably affected the transcriptional pathway induced by the HIF-1?/HIF-1? heterodimer.

SUBMITTER: Minegishi H

PROVIDER: S-EPMC4027554 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Discovery of Indenopyrazoles as a New Class of Hypoxia Inducible Factor (HIF)-1 Inhibitors.

Minegishi Hidemitsu H Fukashiro Shinji S Ban Hyun Seung HS Nakamura Hiroyuki H

ACS medicinal chemistry letters 20130127 2

The indenopyrazole framework was investigated as a new class of HIF-1α inhibitors. Indenopyrazole 2l was found to most strongly inhibit the hypoxia-induced HIF-1α transcriptional activity (IC50 = 0.014 μM) among all of the known compounds having relatively simple structures, unlike manassantins. Indenopyrazole 2l suppressed HIF-1α transcriptional activity without affecting both HIF-1α protein accumulation and HIF-1α/HIF-1β heterodimerization in nuclei under the hypoxic conditions, suggesting tha ...[more]

PMID: 24900662

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