transcription factor 1

Transcription factor-IN-1 (Compound 4e) 作为一种转录因子抑制剂,通过拮抗pentylenetetrazole (PTZ) 显示出其抗惊厥活性(ED50=34.5 mg kg).此外,该化合物在大鼠模型中还展现了抗抑郁活性.

CSRM617 hydrochloride 是转录因子ONECUT2(OC2，雄激素受体 AR 的主要调节剂) 的选择性小分子抑制剂，在 SPR 测定中Kd 为 7.43 uM，直接与 OC2-HOX 结构域结合。CSRM617 hydrochloride 通过裂解 Caspase-3 和 PARP 诱导细胞凋亡 (apoptosis)。CSRM617 hydrochloride 在小鼠的前列腺癌模型中具有良好的耐受性。

DB1976 是一种 DB270 的硒烯类似物，是一种高效且可渗透细胞的转录因子 PU.1 的抑制剂。在体外，DB1976 有效抑制 PU.1 结合 (IC50 为 10 nM)，可强烈抑制 PU.1 DNA 复合物 (具有高 DB1976-λB 亲和力，KD 为 12 nM)。DB1976 具有诱导细胞凋亡的作用。

CCG-257081 (MRTF SRF-IN-1) 是心肌素相关转录因子和血清反应因子 (MRTF SRF) 的抑制剂,通过抑制 Rho MRTF SRF 通路来发挥作用。CCG-257081 已在多个小鼠模型中显示出预防博莱霉素诱导的纤维化的功效。CCG-257081 可用于预防癌症和纤维化的研究。

Caffeic Acid Phenethyl Ester (Phenylethyl Caffeate) 是咖啡酸的苯乙醇酯，是蜂巢蜂胶的生物活性成分。它抑制核转录因子 NF-kappa B 的激活，具有抗肿瘤、细胞保护和免疫调节活性。它抑制 PDGF 诱导的血管平滑肌细胞增殖。

Bufalin 是蟾酥中的一种成分，是Na+ K+-ATPase 抑制剂，具有抗肿瘤活性，可与其基 α1、α2 和 α3 结合，Kd 值分别为 42.5、45 和 40 nM。

Ganoderic acid A 能够抑制 JAK-STAT3信号通路，也能抑制细胞增殖，存活率和 ROS。 它对人骨肉瘤 HOS 和MG-63细胞具有增殖抑制、凋亡和侵袭抑制作用。

Oroxylin A (Baicalein 6-methyl ether) 是一种有活性的黄酮，具有较强的抗癌作用。

NFAT Transcription Factor Regulator-1 是 IL-2 合成 的抑制剂，IC50 值为182 nM。

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。

DB1976 dihydrochloride (DB1976 2HCl) ，一种转录因子 PU.1 抑制剂，具有潜在抗炎活性，可在体内实验中减缓小鼠的炎症和纤维化，改善了葡萄糖稳态和血脂异常。DB1976 dihydrochloride 促进细胞凋亡，可用于研究代谢功能障碍和非酒精性脂肪性肝炎。

TFCP2L1-IN-1是一种TFCP2L1转录因子抑制剂，能够调节细胞的增殖和多能性。TFCP2L1（转录因子CP2样1）在维持小鼠和人类胚胎干细胞（ESC）的多能性中起关键作用。能够通过抑制STAT3 NANOG通路促进Sorafenib的抗肿瘤作用。

UMB-32 是一种有效的选择性BRD4抑制剂，结合 BRD4 的Kd 为 550 nM，IC50为 637 nM。UMB-32 还显示出对TAF1的效力，TAF1是一种含溴结构域的转录因子。

Ro24-7429 是一种有效的口服活性 HIV-1 反式激活蛋白 Tat 拮抗剂和一种矮小相关转录因子 1 的抑制剂。Ro24-7429 具有抗 HIV、抗纤维化和抗炎作用。

Negletein (7-O-Methylbaicalein) 一种神经保护剂，可增强神经生长因子的作用并诱导 PC12 细胞中的神经突生长。它通过抑制TNF-α和IL-1β表现出抗炎活性，其 IC50值分别为 16.4 和 10.8 μM。它还具有抗菌、抗缺氧和抗阿尔茨海默病活性。

Darinaparsin is a dimethylated arsenic linked to glutathione. It is cytotoxic to DU145, LNCaP, and PC3 prostate cancer cells (IC50s = 5-10 µM) and patient-derived primary prostate cancer cells (IC50s = 2.5-20 µM), as well as Jurkat T cell lymphoma and L540 Hodgkin lymphoma cells (IC50s = 2.7 and 1.3 µM, respectively). [1][2] It decreases the tumor-initiating subpopulation in DU145 and PC3 cells and halts the cell cycle in the G2 M phase. Darinaparsin decreases transcription of Gli-2, a transcription factor that mediates Sonic hedgehog signaling, when used at a concentration of 1.5 but not 3 µM. It decreases SHP1 phosphatase activity and increases ERK phosphorylation. [2] Darinaparsin reduces tumor growth in DU145 and PC3 prostate cancer mouse xenograft models when administered at a dose of 100 mg kg every other day.[1]

Bile acids are essential for solubilization and transport of dietary lipids, are the major products of cholesterol catabolism, and are physiological ligands for farnesoid X receptor (FXR), a nuclear receptor that regulates genes involved in lipid metabolism.1They are also inherently cytotoxic, as physiological imbalance contributes to increased oxidative stress.2,3Bile acid-controlled signaling pathways are promising novel targets to treat such metabolic diseases as obesity, type II diabetes, hyperlipidemia, and atherosclerosis.Guggulsterone, derived from resin of the guggul tree, is a competitive antagonist of FXR bothin vitroandin vivo.4Thecisstereoisomer of guggulsterone, (E)-guggulsterone, decreases chenodeoxycholic acid (CDCA)-induced FXR activation with an IC50value of 15 μM.5,6By inhibiting CDCA-induced transactivation of FXR, guggulsterone lowers low-density lipoprotein cholesterol and triglyceride levels in rodents fed a high cholesterol diet.4 1.Makishima, M., Okamoto, A.Y., Repa, J.J., et al.Identification of a nuclear receptor for bile acidsScience2841362-1365(1999) 2.Barbier, O., Torra, I.P., Sirvent, A., et al.FXR induces the UGT2B4 enzyme in hepatocytes: A potential mechanism of negative feedback control of FXR activityGastroenterology1241926-1940(2003) 3.Tan, K.P., Yang, M., and Ito, S.Activation of nuclear factor (erythroid-2 like) factor 2 by toxic bile acids provokes adaptive defense responses to enhance cell survival at the emergence of oxidative stressMol. Pharmacol.72(5)1380-1390(2007) 4.Urizar, N.L., Liverman, A.B., Dodds, D.T., et al.A natural product that lowers cholesterol as an anatagonist ligand for FXRScience296(5573)1703-1706(2002) 5.Cui, J., Huang, L., Zhao, A., et al.Guggulsterone is a farnesoid X receptor antagonist in coactivator association assays but acts to enhance transcription of bile salt export pumpThe Journal of Biological Chemisty278(12)10214-10220(2003) 6.Wu, J., Xia, C., Meier, J., et al.The hypolipidemic natural product guggulsterone acts as an antagonist of the bile acid receptorMolecular Endocrinology16(7)1590-1597(2002)

Lysine-specific demethylase inhibitor (1C) (LSD inhibitor (1C)) is an inhibitor of LSD1, a repressive demethylase selective for histone H3 lysine 4 (H3K4).1,2LSD inhibitor (1C) inhibits LSD1 activity by 85.9% when used at a concentration of 10 μM.1It increases the level of H3K4 methylation, including H3K4me1 and H3K4me2 but not H3K9me2 levels, in HCT116 human colon carcinoma cells.2LSD inhibitor (1C) also induces re-expression of the Wnt signaling pathway proteins secreted frizzle-related protein 1 (SFRP1), SFRP4, and SFRP5, as well as the transcription factor GATA5, which are aberrantly silenced in HCT116 cells.

N-3-hydroxydecanoyl-DL-Homoserine lactone is a bacterial quorum-sensing molecule.1It activates SdiA (EC50= 0.6 μM), a transcription factor that detects N-acyl homoserine lactones (AHLs), in the 14028 pJNS25 strain ofS. enterica.2 1.Fekete, A., Frommberger, M., Rothballer, M., et al.Identification of bacterial N-acylhomoserine lactones (AHLs) with a combination of ultra-performance liquid chromatography (UPLC), ultra-high-resolution mass spectrometry, and in-situ biosensorsAnal. Bioanal. Chem.387455-467(2007) 2.Janssens, J.C.A., Metzger, K., Daniels, R., et al.Synthesis of N-acyl homoserine lactone analogues reveals strong activators of SdiA, the Salmonella enterica serovar Typhimurium LuxR homologueAppl. Environ. Microb.73(2)535-544(2007)

N-3-oxo-pentanoyl-L-Homoserine lactone is a chain-shortened derivative of the bacterial quorum sensing signaling molecule N-3-oxo-octanoyl-L-homoserine lactone .1It inhibits binding of the autoinducer N-3-oxo-hexanoyl homoserine lactone toE. colicontaining the transcription factor LuxR when used at a concentration of 230 nM.2It acts as an autoinducer to activate theV. fischeriluminescence system inE. coliwhen used at concentrations ranging from 20 to 200 nM. 1.Chhabra, S.R., Stead, P., Bainton, N.J., et al.Autoregulation of carbapenem biosynthesis in Erwinia carotovora by analogues of N-(3-oxohexanoyl)-L-homoserine lactoneJ. Antibiot. (Tokyo)46(3)441-454(1993) 2.Schaefer, A.L., Hanzelka, B.L., Eberhard, A., et al.Quorum sensing in Vibrio fischeri: Probing autoinducer-LuxR interactions with autoinducer analogsJ. Bacteriol.178(10)2897-2901(1996)

SGC2085 HCl 是一种有效的选择性辅激活剂相关的精氨酸甲基转移酶 1 (CARM1) 抑制剂，IC50 为 50 nM，选择性比其他 PRMT 高出数倍。 CARM1 是结直肠癌中 Wnt β-catenin 转录和肿瘤转化的重要正调节因子，也是雌激素刺激的乳腺癌生长的关键因素，其耗竭导致体内髓性白血病细胞增殖减少。

HXR9 is a cell-permeable peptide that acts as a competitive antagonist of the HOX PBX interaction. It effectively inhibits the binding between HOX proteins and the transcription factor PBX, specifically in paralogue groups 1 to 8. HXR9 selectively impairs cell proliferation and induces apoptosis in cells with a high expression of the HOXA PBX3 genes, for instance, MLL-rearranged leukemic cells.

T-5224 是选择性的转录因子c-Fos activator protein (AP)-1抑制剂，具有抗炎作用，能够特异性抑制 c-Fos c-Jun 的 DNA 结合活性，但对其他转录因子的结合活性无影响。它抑制 IL-1β 诱导的 Mmp-3、Mmp-13、Adamts-5 转录上调。

Mithramycin A (Plicamycin) 是一种dna 结合的抗肿瘤抗生素，选择性特异性蛋白1 (Sp1)抑制剂，通过降低Sp1蛋白抑制多种肿瘤的生长。特异性蛋白1 (Sp1)是一种锌指转录因子，调节多种细胞功能，促进肿瘤进展。