Sigma-Aldrich Gliocidin，≥98%（HPLC），粉末，IMPDH 2抑制剂

产品概述

≥98%（HPLC），粉末，IMPDH 2抑制剂

应用领域

Gliocidin可用于研究其通过抑制细胞增殖和调节代谢途径对胶质母细胞瘤的作用。PMID 39567689它也可用于通过间接抑制肌苷一磷酸脱氢酶2（IMPDH 2）靶向从头嘌呤合成途径来诱导胶质母细胞瘤中的肿瘤细胞死亡。

生化/生理作用

Gliocidin is a potent and low-toxic BBB-permeable prodrug that targets glioblastoma by depleting guanylates via IMPDH2 inhibition; enhances effects with temozolomide. Gliocidin, a nanomolar-potent prodrug (IC50 ~9.17 nM under Nam-depleted conditions), inhibits IMPDH2, disrupting guanine nucleotide synthesis, which is crucial for tumor DNA and RNA production. Activated via the NAD+ salvage pathway into gliocidin-adenine dinucleotide (9-AD), it selectively depletes guanylate in tumor cells, leading to cell death. Gliocidin demonstrates effective blood-brain barrier penetration (brain/plasma ratio ~7.75) and significantly reduces glioblastoma growth in vivo at 50 mg/kg intraperitoneally, twice daily, without observed toxicity. Sensitivity to nicotinamide levels (IC50 increases to 35.7 μM with 1 mM Nam) underscores its pathway dependence. Combined with temozolomide (50 mg/kg/day), gliocidin′s efficacy improves through NMNAT1 upregulation, enhancing 9-AD formation and maintaining a strong safety profile. Gliocidin is known to modulate mTOR complex 1 (mTORC1) signaling and impact purine metabolism.PMID 39567689

技术规格