title: 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-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 that 2l probably affected the transcriptional pathway induced by the HIF-1α/HIF-1β heterodimer.
authors.affiliation: Department of Chemistry, Faculty of Science, Gakushuin University , Mejiro, Toshima-ku, Tokyo 171-8588, Japan.
authors.forename: Hidemitsu
authors.initials: H
authors.lastname: Minegishi
authors.affiliation: Department of Chemistry, Faculty of Science, Gakushuin University , Mejiro, Toshima-ku, Tokyo 171-8588, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Fukashiro
authors.affiliation: Department of Chemistry, Faculty of Science, Gakushuin University , Mejiro, Toshima-ku, Tokyo 171-8588, Japan.
authors.forename: Hyun Seung
authors.initials: HS
authors.lastname: Ban
authors.affiliation: Department of Chemistry, Faculty of Science, Gakushuin University , Mejiro, Toshima-ku, Tokyo 171-8588, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakamura
keywords: HIF-1; indenopyrazole; inhibitor; transcriptional activity