1-(2,4-二氯苄基)-1H-吲唑-3-碳酰肼

概述生物活性靶点体外研究体内研究 1-(2,4-二氯苄基)-1H-吲唑-3-碳酰肼试剂级价格

CAS号:252025-52-8
英文名:Adjudin
中文名:1-(2,4-二氯苄基)-1H-吲唑-3-碳酰肼
CBNumber:CB51331593
分子式:C15H12Cl2N4O
分子量:335.19
MOL File:252025-52-8.mol

1-(2,4-二氯苄基)-1H-吲唑-3-碳酰肼化学性质

密度 :1.51±0.1 g/cm3(Predicted)
储存条件 :Store at -20°C
溶解度 :DMSO:34.56(Max Conc. mg/mL);103.11(Max Conc. mM)
DMF:30.0(Max Conc. mg/mL);89.5(Max Conc. mM)
DMF:PBS (pH 7.2) (1:20):0.05(Max Conc. mg/mL);0.15(Max Conc. mM)
形态 :A crystalline solid
酸度系数(pKa) :11.88±0.30(Predicted)
颜色 :White to off-white

1-(2,4-二氯苄基)-1H-吲唑-3-碳酰肼性质、用途与生产工艺

概述 Adjudin【男用口服避孕药（1-(2，4-二氯苄基)-1H-吲唑-3-碳酰肼）】系Lonidamine衍生物。以往在大鼠、家兔及猎犬研究证明Adjudin【男用口服避孕药（1-(2，4-二氯苄基)-1H-吲唑-3-碳酰肼）】是以种潜在的男性口服避孕药，它通过干扰睾丸支持细胞和生精细胞的粘附连接，由此引起成熟前生精上皮精子细胞释放，导致雄性不育。然而，Adjudin【男用口服避孕药（1-(2，4-二氯苄基)-1H-吲唑-3-碳酰肼）】是否干扰人精子的受精能力及其可能的作用机制，至今尚未研究。
生物活性 Adjudin (AF-2364) 是一种有效的男性避孕药，也是一种有效的 Cl⁻ channels 的阻滞剂。Adjudin 通过抑制 NF-κB p65核易位和DNA结合活性以及 ERK MAPK磷酸化而具有抗炎特性。
靶点
Target Value
Cl⁻ channel
()
NF-κB
()
ERK
()
体外研究

Adjudin is a potent blocker of Cl ^- channels: disrupting Cl ^- ion transport function results in a decline in sperm capacitation and fertilizing ability in humans in vitro. Adjudin (ADD) is a mitochondria inhibitor. Adjudin is a molecule that mediates adherens junction disruption at the Sertoli-germ cell interface. To investigate the effect of Adjudin on cancer cells, more than ten different types of human or mice cancer cell lines are treated with increasing concentrations of Adjudin and the cell proliferation is measured by the modified MTT assay. Adjudin inhibits cell proliferation in a dose dependent manner in SGC-7901 (human gastric adenocarcinoma cell), MDA-MB-231 (human breast adenocarcinoma cell), Smmc-7721 (human hepatoma cell) and MIA Paca-2 (human pancreatic adenocarcinoma cell) cells. The IC ₅₀ of Adjudin is determined to be 58.0 µM, 13.8 µM, 72.3 µM and 52.7 µM against SGC-7901, MDA-MB-231, Smmc-7721 and MIA Paca-2 cells, respectively, after treatment for 24 h. Similar results are obtained in other human and mice cancer cell lines. The IC ₅₀ of Adjudin in A549 cells and PC3 cells is 63.1 µM and 93.0 µM, respectively. For WI-38 and BPH-1 cells, the IC ₅₀ of Adjudin can be observed at more than 300 µM and 200 µM, respectively, which is about 5 times and 2 times more than that for the cancer cell lines A549 and PC3.
体内研究

To determine whether Adjudin can inhibit lung and prostate cancer growth in vivo, the effect of Adjudin is tested in a subcutaneous model of lung and prostate cancer. Human lung carcinoma cells A549 and prostate carcinoma cells PC3 are injected into athymic nude mice subdermally at the lower back site respectively. Mice are then randomized into two treatment groups with similar mean tumor sizes: Adjudin and vehicle (control). Approximately 2 weeks after tumor inoculation Adjudin is injected intraperitoneally once every three days in lung carcinoma cells and every other day in prostate carcinoma cells at 100 mg/kg. Adjudin treatment can be well tolerated in rodent. And Adjudin-treated mice show significant tumor growth inhibition compared with the control group (P<0.0001 in the human lung carcinoma cells A549 and P=0.006 in the prostate carcinoma cells PC3).