mrc 1

Nemorosone is a polycyclic polyprenylated acylphloroglucinol (PPAP) originally isolated from C. rosea that has antiproliferative properties.1 Nemorosone inhibits growth of NB69, Kelly, SK-N-AS, and LAN-1 neuroblastoma cells (IC50s = 3.1-6.3 μM), including several drug-resistant clones, but not MRC-5 human embryonic fibroblasts (IC50 = >40 μM).2 It increases DNA fragmentation in LAN-1 cells in a dose-dependent manner, and decreases N-Myc protein levels and phosphorylation of ERK1 2 by MEK1 2. Nemorosone also inhibits growth of Capan-1, AsPC-1, and MIA-PaCa-2 pancreatic cancer cells (IC50s = 4.5-5.0 μM following a 72-hour treatment) but not human dermal and foreskin fibroblasts (IC50s = >35 μM).1 It induces apoptosis, abolishes the mitochondrial membrane potential, and increases cytosolic calcium concentration in pancreatic cancer cells in a dose-dependent manner. Nemorosone activates the caspase cascade in a dose-dependent manner and inhibits cell cycle progression, increasing the proportion of cells in the G0 G1 phase, in both neuroblastoma and pancreatic cancer cells.1,2 Nemorosone (50 mg kg, i.p., per day) also reduces tumor growth in an MIA-PaCa-2 mouse xenograft model.3References1. Holtrup, F., Bauer, A., Fellenberg, K., et al. Microarray analysis of nemorosone-induced cytotoxic effects on pancreatic cancer cells reveals activation of the unfolded protein response (UPR). Br. J. Pharmacol. 162(5), 1045-1059 (2011).2. Díaz-Carballo, D., Malak, S., Bardenheuer, W., et al. Cytotoxic activity of nemorosone in neuroblastoma cells. J. Cell. Mol. Med. 12(6B), 2598-2608 (2008).3. Wold, R.J., Hilger, R.A., Hoheisel, J.D., et al. In vivo activity and pharmacokinetics of nemorosone on pancreatic cancer xenografts. PLoS One 8(9), e74555 (2013). Nemorosone is a polycyclic polyprenylated acylphloroglucinol (PPAP) originally isolated from C. rosea that has antiproliferative properties.1 Nemorosone inhibits growth of NB69, Kelly, SK-N-AS, and LAN-1 neuroblastoma cells (IC50s = 3.1-6.3 μM), including several drug-resistant clones, but not MRC-5 human embryonic fibroblasts (IC50 = >40 μM).2 It increases DNA fragmentation in LAN-1 cells in a dose-dependent manner, and decreases N-Myc protein levels and phosphorylation of ERK1 2 by MEK1 2. Nemorosone also inhibits growth of Capan-1, AsPC-1, and MIA-PaCa-2 pancreatic cancer cells (IC50s = 4.5-5.0 μM following a 72-hour treatment) but not human dermal and foreskin fibroblasts (IC50s = >35 μM).1 It induces apoptosis, abolishes the mitochondrial membrane potential, and increases cytosolic calcium concentration in pancreatic cancer cells in a dose-dependent manner. Nemorosone activates the caspase cascade in a dose-dependent manner and inhibits cell cycle progression, increasing the proportion of cells in the G0 G1 phase, in both neuroblastoma and pancreatic cancer cells.1,2 Nemorosone (50 mg kg, i.p., per day) also reduces tumor growth in an MIA-PaCa-2 mouse xenograft model.3 References1. Holtrup, F., Bauer, A., Fellenberg, K., et al. Microarray analysis of nemorosone-induced cytotoxic effects on pancreatic cancer cells reveals activation of the unfolded protein response (UPR). Br. J. Pharmacol. 162(5), 1045-1059 (2011).2. Díaz-Carballo, D., Malak, S., Bardenheuer, W., et al. Cytotoxic activity of nemorosone in neuroblastoma cells. J. Cell. Mol. Med. 12(6B), 2598-2608 (2008).3. Wold, R.J., Hilger, R.A., Hoheisel, J.D., et al. In vivo activity and pharmacokinetics of nemorosone on pancreatic cancer xenografts. PLoS One 8(9), e74555 (2013).

BRC4wt是一种从人类BRCA2的BRC4重复区(1521-1536)衍生而来的乙酰化肽，并且是BRCA2与RAD51之间的蛋白质-蛋白质相互作用的抑制剂。当与阳离子穿膜肽(Arg)9结合时，BRC4wt缩短了体外DNA复制轨迹长度，并降低了由DNA拓扑异构酶I抑制剂坎普特西汀引起的DNA损伤的同源修复频率，同时也增强了聚(ADP-核糖)聚合酶(PARP)抑制剂奥拉帕尼在HeLa人类宫颈癌细胞和U2OS人类骨肉瘤细胞中诱导的细胞死亡，但在非癌症细胞hTERT RPE-1、MRC-5或MCF-10A中则不然。

HP661是一种针对线粒体复合物I（也称为NADH脱氢酶）的抑制剂，对复合物I具有选择性，以1 µM的浓度抑制其77.6%，而对复合物III抑制率为28.1%，对复合物II和IV则无抑制作用。HP661特异性降低具有高水平氧化磷酸化作用的人类肺癌细胞H460、NCI H441及对trametinib耐药的A549细胞的生存能力（IC50分别为10.6、29.7和15.1 nM），相较于氧化磷酸化水平低的NCI H358人类肺癌细胞（IC50 >10,000 nM）以及非癌性人类胰腺正常上皮细胞（HPNE）和MRC-5人类胎肺成纤维细胞（两者的IC50均>10,000 nM）。当以每天两次，每次30 mg/kg的剂量给药时，HP661在H460小鼠异种移植模型中减少肿瘤体积，并对trametinib引导的肿瘤生长减少产生加成效应。

Galectin-3 galectin-8-IN-1 (Compound 53) 是抑制Galectin-3和galectin-8C末端结构域的双重抑制剂，其Kd值分别为4.12 μM和6.04 μM。该化合物有效抑制MRC-5肺成纤维细胞的迁移，可用于癌症和组织纤维化的研究。

NPD-2975（化合物30）是一款口服活性的抗锥虫药物，用于治疗非洲人类锥虫病（HAT）。在MRC-5人肺成纤维细胞及T. b. brucei感染的小鼠模型中，NPD-2975毒性低。此化合物展现了良好的代谢稳定性，在体外对T. b. brucei IC500抑制浓度为70 nM。NPD-2975还可抑制CYP450酶，对CYP1A2和CYP2C19的IC50分别为0.16 μM和0.42 μM。

MtTMPK-IN-2 (compound 15)为一高效MtbTMPK抑制剂，IC50值达1.1 μM。该化合物对MtbH37Rv表现出抑制活性（MIC = 12.5 μM），同时对人成纤维细胞MRC-5显示出一定细胞毒性（EC50= 6.1 μM）。MtTMPK-IN-2适用于结核病研究。

Galectin-3 galectin-8-IN-2（Compound 57）是一种针对Galectin-3和galectin-8C末端结构域的双重抑制剂，其Kd值分别为12.8 μM和2.06 μM。该化合物能够抑制MRC-5肺成纤维细胞的迁移，适用于癌症和组织纤维化研究领域。

MtTMPK-IN-3（compound 25）是一种针对结核分枝杆菌胸苷酸激酶（MtbTMPK）的有效抑制剂，具有0.12 μM的IC50值。该化合物对MtbH37Rv展示出了抑制效果（MIC=12.5 μM），同时对人成纤维细胞MRC-5显示出一定的细胞毒性（EC50=12.5 μM）。MtTMPK-IN-3适用于结核病研究领域。

MtTMPK-IN-1 (compound 3) is a highly effective inhibitor of Mycobacterium tuberculosis thymidylate kinase (Mt TMPK), exhibiting an IC50 value of 2.5 μM. It displays moderate to weak activity against Mtb H37Rv while demonstrating low cytotoxicity in human fibroblast cells MRC-5. MtTMPK-IN-1 is a valuable tool for tuberculosis research [1].