European Journal of Medicinal Chemistry (2019)
Update date:2022-08-15
Topics:
Cao, Hengyi
Zhu, Guangya
Sun, Lin
Chen, Ge
Ma, Xinxin
Luo, Xiao
Zhu, Jidong
Isocitrate dehydrogenase 1 (IDH1), which catalyzes the conversion of isocitrate to α-ketoglutarate, is one of key enzymes in the tricarboxylic acid cycle (TCA). Hotspot mutation at Arg132 in IDH1 that alters the function of IDH1 by further converting the α-ketoglutarate(α-KG) to 2-hydroxyglutarate (2-HG) have been identified in a variety of cancers. Because the IDH1 mutations occur in a significant portion of gliomas and glioblastomas, it is important that IDH1 inhibitors have to be brain penetrant to treat IDH1-mutant brain tumors. Here we report the efforts to design and synthesize a novel serial of mutant IDH1 inhibitors with improved activity and the blood-brain barrier (BBB) penetration. We show that compound 5 exhibits good brain exposure and potent 2-HG inhibition in a HT1080-derived mouse xenograft model, which makes it a potential preclinical candidate to treat IDH1-mutant brain tumors.
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Doi:10.3184/030823408X340816
(2008)Doi:10.1002/ejoc.201200237
(2012)Doi:10.1016/j.tet.2008.10.003
(2009)Doi:10.1016/j.tet.2008.10.043
(2009)Doi:10.1016/0039-128X(86)90025-5
(1986)Doi:10.1016/S0040-4020(01)83450-5
(1987)