T37874
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Feglymycin is a 13-amino acid peptide originally isolated from Streptomyces that has antibacterial and antiviral activities. It is active against Gram-positive bacteria (MICs = 32-64 μg/ml) and inhibits HIV viral replication in H9 cells (IC50 = ~5 μM). Feglymycin is also active against clinical isolates of HIV-1 from clades A-D, A/E, and G (EC50s = 0.5-6.7 μM). It interacts with gp120 and inhibits HIV-1 NL4.3 binding to human soluble CD4 (EC50 = 4.4 μM) and to CD4+ SupT1 T cells by 74.5% when used at a concentration of 10.5 μM. Feglymycin inhibits the E. coli peptidoglycan biosynthesis enzymes MurA and MurC (Kis = 3.4 and 0.3 μM, respectively) in a noncompetitive manner. |
T73986
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ONX-0914 (PR-957) TFA 为针对免疫蛋白酶体中的LMP7(低分子量多肽-7)的选择性抑制剂,LMP7为类糜蛋白酶亚单位。该化合物通过抑制细胞因子产生,减缓实验性关节炎进展,并已证实为分枝杆菌蛋白酶体的非竞争性不可逆抑制剂(Ki=5.2 μM)。此外,ONX-0914 TFA 能通过HSF-1介导的p-TEFb活化,激活潜伏的HIV-1。 |
T78987
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SA09-Cu是一种NDM-1的非竞争性抑制剂,具有9.6 nM的IC50。该化合物通过作用于氧化酶的Zn(II)-硫醇盐位点,能将NDM-1转化为无活性形态,从而抵御细菌细胞内的硫醇还原作用。SA09-Cu对于多种产生NDM-1的肠杆菌科碳青霉烯耐药菌株(CRE)表现出明显的抑制作用,有效恢复了美罗培南的活性,并有助于减缓碳青霉烯耐药性的进展。 |
T75870
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PR-39 TFA 是富含脯氨酸和精氨酸的天然抗菌肽,是一种非竞争性,可逆和变构的蛋白酶体 (proteasome) 抑制剂。PR-39 TFA 可逆地结合到蛋白酶体的 α7 亚基上,并通过泛素-蛋白酶体途径阻断 NF-κB 抑制剂 IκBα 的降解。PR-39 TFA 刺激小鼠的血管生成,抑制炎症反应并显着减小心肌梗死面积。 |
T74088
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Fludarabine triphosphate (F-ara-ATP) trisodium 是Fludarabine 的活性代谢物,是一种有效的、非竞争性的、特异性的DNA 引发酶 (DNA primase) 抑制剂,其IC50为 2.3 μM,Ki 为 6.1 μM。Fludarabine triphosphate trisodium 通过阻断 DNA 引发酶和引物 RNA 形成抑制 DNA 合成 (DNA synthesis)。Fludarabine triphosphate trisodium 可抑制核糖核苷酸还原酶和DNA 聚合酶,导致细胞凋亡 (apoptosis)。 |
T37374
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URB754 is a potent and noncompetitive inhibitor of monoacylglycerol lipase (MAGL), exhibiting an IC50 value of 200 nM for the recombinant rat brain enzyme. However, it does not inhibit human recombinant, rat brain, or mouse brain MAGL at concentrations up to 100 μM. There is evidence that the MAGL inhibitory activity of URB754 may be attributed to the impurity bis(methylthio)mercurane (IC50 = 11.9 nM for rat recombinant MAGL) that is found in commercial preparations. URB754 inhibits rat brain fatty acyl amide hydrolase (FAAH) with an IC50 value of 32 μM and binds weakly to the rat central cannabinoid (CB1) receptor with an IC50 value of 3.8 μM. It does not inhibit COX-1 or COX-2 at concentrations up to 100 μM. Inhibition of MAGL hydrolysis of 2-arachidonoyl glycerol (2-AG) is associated with enhanced stress-induced analgesia and may represent a novel drug target in pain and stress management. |
T79399
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GABA Receptor
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E2730是一种针对γ-氨基丁酸(GABA)转运蛋白1(GAT1)的非竞争性选择性抑制剂,它能口服有效且有抗癫痫的作用。这种化合物能够随着环境中GABA水平的增加而增强其抑制GAT1的活性,从而有选择性地抑制GABA的回收。在实验模型中,E2730 (剂量范围为5-50 mg/kg; 经口给药) 在大鼠杏仁核点燃模型和小鼠的多种癫痫模型中,包括角膜点燃 (5-50 mg/kg)、耐药的6Hz-44mA精神运动癫痫 (5-50 mg/kg)、脆性X综合征 (2.5-300 mg/kg) 及Dravet综合征模型 (10 mg/kg, 20 mg/kg),展现了显著的体内活性。 |