replication protein a

TDRL-551 是一种新型有效的复制蛋白A (RPA) 抑制剂 (IC50=18 µM)，具有潜在的抗癌活性。TDRL-551 对 RPA-DNA 相互作用有抑制作用，提高以铂为基础的肺癌和卵巢癌化疗的疗效。

Daunorubicin hydrochloride (Rubidomycin hydrochloride) 是一种蒽环类氨基糖苷类化合物，一种拓扑异构酶 II (Topo II) 抑制剂。Daunorubicin hydrochloride 可以抑制 DNA 和 RNA 的合成，具有抗肿瘤活性。

2'-O-Methylcytidine 是 2'-代核苷，可抑制 HCV 复制。 它在体外抑制 NS5B 催化的 RNA 合成，其抑制方式是与底物核苷三磷酸竞争。

N-Acetyl-L-cysteine ethyl ester (NACET) 是氨基酸-l-半胱氨酸的衍生物。N-Acetyl-L-cysteine ethyl ester 已被证明具有广泛的生化和生理作用，包括抑制蛋白质合成、抑制DNA 复制和诱导细胞凋亡。它还被证明具有抗炎、抗氧化和抗癌活性

Tubercidin (Sparsomycin A) 是从Streptomyces tubercidicus 得到的抗生素，抑制粪链球菌生长的IC50值为 0.02 μM。它是腺苷磷酸化酶的弱抑制剂，并干扰腺苷和 AMP 的磷酸化。它有抗病毒作用。

Dasabuvir (ABT-333) 是丙型肝炎病毒非结构蛋白 5B 的非核苷抑制剂，是一种 RNA 依赖性 RNA 聚合酶，具有抗 HCV 的潜在活性。

Nucleozin 靶向流感 A 核蛋白，这是一种病毒复制所必需的多功能 RNA 结合蛋白。

PF-3450074 (PF-74)是 HIV-1 衣壳蛋白的特异性抑制剂，可广谱抑制 HIV 分离株。它在 HIV-1 感染的早期阶段起作用，通过与 CPSF6 和 NUP153 的结合直接竞争来抑制病毒复制，并阻断病毒生命周期的脱膜，组装和逆转录步骤。

Beclabuvir (BMS-791325) 是一种高效的 NS5A 复制复合物抑制剂，抑制 HCV 基因型 1，2，4，5 表达的 NS5B 蛋白活性，可用于研究 HCV 感染。

BRD5631 是一种自噬 (autophagy) 增强剂，通过与 mTOR 无关的通路来增强自噬。BRD5631 能够影响先前与自噬相关的几种细胞疾病表型，包括蛋白聚集、细胞存活、细菌复制和炎性因子的产生。BRD5631可以作为一种有价值的工具，用于研究自噬在细胞稳态和疾病中的作用。

Cdc7-IN-5 是一种有效的 Cdc7 激酶抑制剂。Cdc7 是一种丝氨酸苏氨酸蛋白激酶酶，在细胞周期中对 DNA 复制的启动至关重要。

IR415 选择性地与 HBx 相互作用 (Kd=2 nM) 并阻断 HBV 介导的 RNAi 抑制，逆转 HBx 蛋白对 Dicer 核糖核酸内切酶活性的抑制作用。IR415 具有抗 HBV 的活性。

S119-8 是一种广谱甲型和乙型流感病毒抑制剂，抑制多种乙型流感病毒和耐奥司他韦的甲型流感病毒。

Pentamethylmelamine，作为hexamethylmelamine的主要代谢产物，具有抗肿瘤活性。该化合物通过烷基化DNA和其他大分子，并形成DNA内链和DNA-蛋白质交联，从而阻止DNA复制。

TDI-015051 是一种口服有效的 SARS-CoV-2 非结构蛋白 14 (SARS-CoV-2 NSP14) 抑制剂，IC50≤0.15 nM。在 Huh-7.5 细胞 (EC50=11.4 nM) 和表达 ACE2-TMPRSS2 的 A549 细胞 (EC50=64.7 nM) 中能够抑制 SARS-CoV-2 NSP14。此外，TDI-015051 对其他冠状病毒，如 α-hCoV-NL63、α-hCoV-229E 和 β-hCoV-MERS，也有抑制作用，IC50分别为 1.7、2.6 和 3.6 nM。通过与SAH稳定的cap口袋结合，TDI-015051 可抑制病毒 RNA 甲基化和病毒复制，并在小鼠模型中显示出抗感染活性。

RJS308 是一种环孢菌素 A (cyclosporin A) 的PROTAC降解剂，具有284 nM的DC50。RJS308 抑制HIV-1和HCV的复制，从而展现出抗病毒活性。(Pink: ligand for target proteinCypA ligand-2; Black: linker; Blue: ligand for E3ligaseVHL(S,R,S)-AHPC-Me)

YZ51, a novel potent inhibitor of ribonucleotide reductase (RR), inhibits hepatitis B virus replication by targeting ribonucleotide reductase M2 protein.

Disoxaril (BRN 3626820, WIN 51711) is an anti-picornavirus agent that inhibits enterovirus replication by binding to a hydrophobic bag within the VP1 coat protein, thereby stabilizing virions and preventing their uncoating. When used in combination with A

Paritaprevir free base (ABT-450) 是一种口服生物可利用的合成酰基磺酰胺抑制剂，可抑制丙型肝炎病毒 (HCV) 蛋白酶复合物，由非结构蛋白 3 和 4A (NS3 NS4A) 组成，对 HCV 基因型 1 具有潜在活性。 给药后，paritaprevir 可逆地结合 HCV NS3 NS4A 蛋白酶的活性中心和结合位点，并阻止 NS3 NS4A 蛋白酶介导的多蛋白成熟。这会破坏病毒蛋白的加工和病毒复制复合物的形成，从而抑制病毒在 HCV 基因型 1 感染的宿主细胞中的复制。 NS3 是一种丝氨酸蛋白酶，对于 HCV 多蛋白内多个位点的蛋白水解切割至关重要，并且在 HCV 核糖核酸 (RNA) 复制过程中起关键作用。 NS4A 是 NS3 的激活因子。 HCV 是属于黄病毒科的一种小的、有包膜的单链 RNA 病毒，感染与肝细胞癌 (HCC) 的发展有关。

FSL-1 TFA, a bacterial-derived toll-like receptor 2 6 (TLR2 6) agonist, enhances resistance to experimental HSV-2 infection[1]. FSL-1 TFA induces MMP-9 production through TLR2 and NF-κB AP-1 signaling pathways in monocytic THP-1 cells[2]. FSL-1 significantly reduces HSV-2 replication in human vaginal epithelial cells (EC)[1].FSL-1 induces significant resistance to experimental genital HSV-2 infection through elaboration of a specific cytokine response profile[1].FSL-1 (50 ng mL, 24 hours) induces MMP-9 expression at both mRNA and protein levels in human monocytic THP-1 cells[2].FSL-1 activates the MAP kinase NF-κB signaling pathway[2]. Cell Viability Assay[1] Cell Line: V11I, V12I or V19I immortalized human vaginal EC FSL-1 application significantly protectes against genital HSV-2 challenge in mice[1]. Animal Model: Female Swiss-Webster mice (weighing 20-25 g)[1] [1]. William A Rose 2nd, et al. FSL-1, a bacterial-derived toll-like receptor 2 6 agonist, enhances resistance to experimental HSV-2 infection. Virol J. 2009 Nov 10;6:195. [2]. Cathryn J Kurkjian,et al. The Toll-Like Receptor 2 6 Agonist, FSL-1 Lipopeptide, Therapeutically Mitigates Acute Radiation Syndrome. Sci Rep. 2017 Dec 11;7(1):17355.

O-11 is an analog of the fully saturated, 14-carbon fatty acid myristic acid, in which the methylene group at position 11 is replaced with oxygen. It is highly effective and selective at killingTrypanosoma brucei, the protozoan parasite responsible for African sleeping sickness, exhibiting an LD50of less than 1 μM in a cell culture assay.1,2The toxic effects of O-11 appear to be caused by its ability to inhibit the incorporation of a single myristate into the GPI anchor of the variant surface glycoprotein (VSG), a protein critical for evading the host immune response.1O-11 exhibits essentially no anti-fungal activity when assayed usingC. neoformans, but does have a minor inhibitory effect on HIV-1 replication in T-lymphocytes.3 1.Doering, T.L., Raper, J., Buxbaum, L.U., et al.An analog of myristic acid with selective toxicity for African trypanosomesScience2521851-1854(1991) 2.Doering, T.L., Lu, T., Werbovetz, K.A., et al.Toxicity of myristic acid analogs toward African trypanosomesProceedings of the National Academy of Sciences of the United States of America919735-9739(1994) 3.Langner, C.A., Lodge, J.K., Travis, S.J., et al.4-Oxatetradecanoic acid is fungicidal for Cryptococcus neoformans and inhibits replication of human immunodeficiency virus IThe Journal of Biological Chemisty267(24)17159-17169(1992)

Boromycin is a boron-containing macrolide antibiotic that has been found in Streptomyces. Boromycin inhibits growth of B. subtilis (MIC = 0.05 μg ml) and induces efflux of potassium ions from B. subtilis without affecting Na+ K+-ATPase activity. It decreases the synthesis of protein, RNA, and DNA in B. subtilis when used at a concentration of 0.05 μg ml. It inhibits the growth of B. halodurans (MIC = 10 ng ml) and inhibits the futalosine pathway of menaquinone synthesis in B. halodurans. Boromycin (3.4 nM) reverses bleomycin-induced cell cycle arrest at the G2 phase in Jurkat cells. It inhibits replication of the HIV-1 strains LAV-1 and RF and the HIV-2 strain LAV-2 in MT-4 cells (IC50s = 0.008, 0.11, and 0.007 μM, respectively). It also inhibits replication of a clinical isolate of HIV-1, strain KK-1, in MT-4 cells and peripheral blood mononuclear cells (PBMCs; IC50s = 0.14 and <0.1 μM, respectively).

High affinity JNK inhibitor (Ki values are 25-50 nM). Inhibits JNK via competitive binding of the ATP-binding site of active, phosphorylated JNK. Exhibits > 40-fold selectivity for JNK over p38, ERK, IKK2, protein kinase C, Lck and ZAP70. Hepatoprotective. Also inhibits HCMV replication. Uehara et al (2004) c-Jun N-terminal kinase mediates hepatic injury after rat liver transplantation. Transplantation. 78 324 PMID:15316358 |Uehara et al (2005) JNK mediates hepatic ischemia reperfusion injury. J.Hepatol. 42 850 PMID:15885356 |Ma et al (2007) A pathogenic role for c-Jun amino-terminal kinase signaling in renal fibrosis and tubular cell apoptosis. J.Am.Soc.Nephrol. 18 472 PMID:17202416 |Ma et al (2009) Blockade of the c-Jun amino terminal kinase prevents crescent formation and halts established anti-GBM glomerulonephritis in the rat. Lab.Invest. 89 470 PMID:19188913 |Zhang et al (2015) The c-Jun N-terminal kinase inhibitor SP600125 inhibits human cytomegalovirus replication. J.Med.Virol. 87 2135 PMID:26058558 |Vasilevskaya et al (2015) Inhibition of JNK sensitizes hypoxic colon cancer cells to DNA-damaging agents. Clin.Cancer.Res. 21 4143 PMID:26023085

Tat-beclin 1, a peptide derived from the autophagy protein beclin 1, is a powerful inducer of autophagy. It interacts with GAPR-1 (GLIPR2), a negative regulator of autophagy. Tat-beclin 1 effectively reduces the buildup of polyglutamine expansion protein aggregates and inhibits the replication of various pathogens, such as HIV-1, in laboratory experiments. In addition, it has demonstrated the ability to decrease mortality in mice infected with chikungunya (CHIKV) or West Nile virus (WNV).