POMHEX 是一个消旋混合物，是具有细胞渗透性的 HEX 的 POM 前体药物，是ENO2 的特异性抑制剂。POMHEX 对ENO1 缺失的细胞表现出低纳摩尔级别活性，并对 ENO1 缺失的肿瘤模型表现出良好的抗癌效果。POMHEX 是有效的糖酵解抑制剂。
POMHEX, a racemic mixture and a cell-permeable pivaloyloxymethyl (POM) prodrug of HEX, is a potent, ENO2-specific inhibitor of enolase. POMHEX exhibits low-nanomolar potency against ENO1-deleted cells in vitro and is capable of eradicating ENO1-deleted xenografted tumours in vivo. POMHEX is a potent glycolysis inhibitor[1].
POMHEX (78 nM, 8h) minimally impacts ENO1-WT glioma cells but profoundly affected ENO1-deleted cells[1].POMHEX (0-720 nM) selectively induces energy stress, inhibits proliferation and triggers apoptosis in ENO1-deleted glioma cells[1].
POMHEX (i.v., ip) injections are consistently tolerated without haemolytic anaemia at doses of up to 10 mg per kg (body weight) per day. POMHEX (i.v., 35 mg/kg) results in lethargy that prompted veterinarians to perform euthanasia[1].POMHEX is rapidly hydrolysed to HemiPOMHEX in mouse plasma ex vivo, with a half-lifeof approximately 30 s, the half-life in human blood ex vivo was about 9min[1].
[1]. Yu-Hsi Lin, et al. An enolase inhibitor for the targeted treatment of ENO1-deleted cancers. Nat Metab. 2020 Nov 23.
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