Carmofur is a potent inhibitor of rat recombinant acid ceramidase with an IC50 value of 29nM [1]. Carmofur binds to the main protease (Mpro) of SARS-CoV-2, where the carbonyl group is covalently bound to catalytic Cys145 thus inhibiting the activity of Mpro[2]. Carmofur has been widely used to inhibit tumor progression and to block multidrug-resistant Streptococcus pneumoniae infection[3].
In vitro, Carmofur treatment for 24 hours significantly inhibited the proliferation of SJGBM2, CHLA200, and CHLA266 cells with IC50 values of 50µM, 13µM and 15µM, respectively[4]. Carmofur treatment for 12h significantly induced cell death in irradiated U87-10gy cells, accompanied by an increase in ceramide levels[5]. Treatment of U251T cells with 20µM Carmofur for 48 hours significantly promoted cell cycle alterations, induced apoptosis and decreased E2F8 mRNA expression in U251T cells [6].
In vivo, Carmofur treatment via oral administration at a dose of 10mg/kg (twice a day) for 3 days ameliorated the inflammatory responses and promoted the resolution of pulmonary injury in lipopolysaccharide (LPS)-treated mice[7]. Daily intraperitoneal injection of 750µg (dissolved in 100µl corn oil) of Carmofur for 10 days attenuated parasitemia and decreased reticulocyte frequency in mice during Plasmodium yoelii infection [8].
References:
[1] Realini N, Solorzano C, Pagliuca C, et al. Discovery of highly potent acid ceramidase inhibitors with in vitro tumor chemosensitizing activity[J]. Scientific reports, 2013, 3(1): 1035.
[2] Islam M M, Mirza S P. Versatile use of Carmofur: A comprehensive review of its chemistry and pharmacology[J]. Drug Development Research, 2022, 83(7): 1505-1518.
[3] Lyu W, Zhang Y, Zhang Z, et al. Carmofur Exhibits Antimicrobial Activity Against Streptococcus pneumoniae[J]. Antibiotics, 2025, 14(3): 231.
[4] Doan N B, Nguyen H S, Montoure A, et al. Acid ceramidase is a novel drug target for pediatric brain tumors[J]. Oncotarget, 2017, 8(15): 24753.
[5] Doan N B, Nguyen H S, Al-Gizawiy M M, et al. Acid ceramidase confers radioresistance to glioblastoma cells[J]. Oncology Reports, 2017, 38(4): 1932-1940.
[6] Hawkins C C, Jones A B, Gordon E R, et al. Carmofur prevents cell cycle progression by reducing E2F8 transcription in temozolomide-resistant glioblastoma cells[J]. Cell death discovery, 2023, 9(1): 451.
[7] Wu K, Xiu Y, Zhou P, et al. A new use for an old drug: carmofur attenuates lipopolysaccharide (LPS)-induced acute lung injury via inhibition of FAAH and NAAA activities[J]. Frontiers in pharmacology, 2019, 10: 818.
[8] Günther A, Hose M, Abberger H, et al. The acid ceramidase/ceramide axis controls parasitemia in Plasmodium yoelii-infected mice by regulating erythropoiesis[J]. Elife, 2022, 11: e77975.
Carmofur是一种强效的大鼠重组酸性神经酰胺酶抑制剂，IC50值为29nM[1]。Carmofur与SARS-CoV-2的主要蛋白酶（Mpro）结合，Carmofur的羰基与酶催化位点的Cys145共价结合，从而抑制Mpro的活性[2]。Carmofur已被广泛用于抑制肿瘤进展以及阻断多重耐药肺炎链球菌感染[3]。
在体外，Carmofur处理24小时显著抑制了SJGBM2、CHLA200和CHLA266细胞的增殖，IC50值分别为50µM、13µM和15µM[4]。Carmofur处理12小时显著诱导了辐照后U87-10gy细胞的死亡，伴随神经酰胺水平的升高[5]。使用20µM的Carmofur处理U251T细胞48小时，显著促进了细胞周期改变，诱导了细胞凋亡，并降低了细胞中E2F8 mRNA的表达[6]。
在体内，每日口服两次10mg/kg剂量的Carmofur，连续3天，减轻了脂多糖（LPS）处理小鼠的炎症反应并促进了肺损伤的消退[7]。每日腹腔注射750µg的Carmofur（溶于100µl玉米油），连续10天，减轻了Plasmodium yoelii感染小鼠的寄生虫血症并降低了网织红细胞频率[8]。