JBIR-22, an inhibitor for protein-protein interaction of the homodimer of proteasome assembly factor 3.
Proteasome assembling chaperone (PAC) 3 acts as a homodimer and plays an important role in proteasome formation. We screened JBIR-22 (1) as an inhibitor for protein-protein interaction (PPI) of PAC3 homodimer from our natural product library using a protein fragment complementation assay (PCA) with monomeric Kusabira-Green fluorescent protein (mKG) in vitro and found that 1 exhibited potent inhibitory activity against PAC3 homodimerization. Compound 1 showed long-term cytotoxicity against the human cervical carcinoma cell line, HeLa. This is the first report of a PPI inhibitor for proteasome assembly factors.
Izumikawa
Miho
M
Biomedicinal Information Research Center (BIRC), Japan Biological Informatics Consortium (JBIC), 2-4-7 Aomi, Koto-ku, Tokyo 135-0064, Japan.
Hashimoto
Junko
J
Hirokawa
Takatsugu
T
Sugimoto
Satoshi
S
Kato
Taira
T
Takagi
Motoki
M
Shin-Ya
Kazuo
K
D004354:Drug Screening Assays, Antitumor; D005260:Female; D006367:HeLa Cells; D006801:Humans; D015394:Molecular Structure; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects* / Q000378:metabolism; D011506:Proteins / Q000032:analysis* / Q000187:drug effects / Q000378:metabolism; D011760:Pyrrolidinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
C549607:JBIR-22; D011506:Proteins; D011760:Pyrrolidinones; D013764:Tetrahydronaphthalenes; C024509:equisetin; D046988:Proteasome Endopeptidase Complex