Inhibitor demetylazy histonów H3K4, ester etylowy proleku KDM5-C49, który selektywnie reguluje w górę H3K4me3 i hamuje wzrost raka zależny od KDM5.
KDM5-C70 (KDOAM-21) odpowiada prekursorowi estru etylowego selektywnego αKG kompetytywnego inhibitora demetylazy histonowej KDM5 KDM5-C49 (KDOAM-21; KDM5A/B/C/D Ki = 2/1/6.1/3.4 nM vs. KDM4C/6B/3A/2A Ki = 0.51/4.55/2.59/4.4 μM; KDM5A/B/C/D IC50 = 1.1/0.8/3.2/2.7 μM w teście FDH z [αKG] = 1 mM i [E]/[S] = 0.5/15 μM; KDM5A/B/C IC50 = 25/30/59 nM przez alphaLISA z [αKG] = 25 μM i [E]/[S] = 10/100 nM). Leczenie KDM5-C70 selektywnie zwiększa komórkową trimetylację histonu H3 na Lys4 (H3K4me3), ale nie na Lys9/7/36 (5 μM, 3d) i hamuje wzrost raka zależny od KDM5 (o 85%/MCF7/11d, 97%/BT474/24d i 70%/ZR-75-1/24d; 5 μM).
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Journal of medicinal chemistry, 61(7), 3193-3208 (2018-03-15)
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Nasz zespół naukowców ma doświadczenie we wszystkich obszarach badań, w tym w naukach przyrodniczych, materiałoznawstwie, syntezie chemicznej, chromatografii, analityce i wielu innych dziedzinach.
