208260-29-1
中文名称
ZM 336372
英文名称
ZM 336372
CAS
208260-29-1
分子式
C23H23N3O3
分子量
389.45
MOL 文件
208260-29-1.mol
更新日期
2024/05/07 11:47:10
208260-29-1 结构式
基本信息
中文别名
C-RAF抑制剂(ZM 336372)3-(二甲基氨基)-N-[3-[(4-羟基苯甲酰基)氨基]-4-甲基苯基]苯甲酰胺
英文别名
CS-44ZM 336372
Zinc00581684
ZM 336372, >=98%
ZM 336372
ZM-336372
ZM 336372 USP/EP/BP
ZM 336372
ZM-336372
ZINC00581684
ZM 336372 - CAS 208260-29-1 - Calbiochem
N-[5-(3-DIMETHYLAMINOBENZAMIDO)-2-METHYLPHENYL]-4-HYDROXYBENZAMIDE
3-(diMethylaMino)-N-(3-(4-hydroxybenzaMido)-4-Methylphenyl)benzaMide
所属类别
生物化工：Raf 抑制剂物理化学性质
沸点484.4±45.0 °C(Predicted)
密度1.298
储存条件-20°C
溶解度DMSO：>5mg/mL（加热）
酸度系数(pKa)8.31±0.15(Predicted)
形态粉末
颜色白色至米色
敏感性感光
稳定性从购买之日起 2 年内保持稳定。 DMSO 溶液可在 -20°C 下保存长达 1 个月。
常见问题列表
生物活性
ZM 336372是一种有效的，选择性的c-Raf抑制剂，IC50为70 nM，比作用于B-RAF选择性高10倍，对PKA/B/C， AMPK， p70S6等没有抑制作用。体外研究
ZM 336372 shows 10-fold selectivity over B-Raf. ZM 336372 weakly inhibits SAPK2a/p38α and SAPK2b/p38β with IC50 of 2 μM, and is selective over 17 other protein kinases including PKA, PKC, AMPK, p42 MAPK, MKK1, SAPK1/JNK, and CDK1 even at the concentration of up to 50 μM. ZM 336372 does not prevent constitutive as well as growth factor or phorbol ester induced activation of MKKl or p42 MAPK/ERK2. Moreover, ZM 336372 dose not reverse the phenotype of Ras- or Raf-transformed cell lines. ZM 336372 treatment induces >100 activation of c-Raf and the B-Raf isoform, but it does not trigger any activation of MKKI or p42 MAPK/ERKP or induce any increase in the GTP-loading of Ras, suggesting that a feedback control loop exists by which Raf isoforms suppress their own activation, such that inhibition is always counterbalanced by reactivation. ZM 336372-induced activation of c-Raf is not prevented by inhibition of the MAPK cascade, protein kinase C or phosphatidylinositide 3-kinase. ZM 336372 (1 μM) abolishes the upregulation of eNOS after treatment with hydrogen peroxide. ZM 336372 treatment in carcinoid tumor cells results in progressive phosphorylation of Raf-1, mitogen-activated protein kinase 1/2, and extracellular signal-regulated kinase 1/2, and causes a significant reduction of bioactive hormone levels as well as the transcription factor, human achaete-scute homologue-1. Furthermore, ZM 336372 treatment leads to a marked suppression of cellular proliferation and induction of the cell cycle inhibitors p21 and p18. ZM 336372 inhibits the proliferation of pheochromocytoma cells, and suppresses NE vasoactive peptide production. ZM 336372 treatment in HepG2 induces the suppression of proliferation in a dose-dependent manner, suppression of hormone secretion, and up-regulation of cell cycle inhibitors. ZM 336372 also induces apoptosis in pancreatic adenocarcinoma cell lines by inhibiting glycogen synthase kinase-3β through phosphorylation of GSK-3β at Ser 9.生物活性
ZM 336372 (Zinc00581684) 是一种有效的，选择性的c-Raf抑制剂，IC50为70 nM，比作用于B-RAF选择性高10倍，对PKA/B/C， AMPK， p70S6等没有抑制作用。靶点
| Target | Value |
| C-Raf | 70 nM |
体外研究
ZM 336372作用于C-Raf 的选择性是作用于B-Raf的10倍。ZM 336372微弱抑制SAPK2a/p38α和SAPK2b/p38β，IC50 为2 μM，即使在高达50 μM浓度下，对C-Raf的选择性也高于包括PKA，PKC，AMPK，p42 MAPK，MKK1，SAPK1/JNK，和CDK1等17种其他蛋白激酶。ZM 336372不会阻止生长因子或佛波酯诱导的MKKl或p42 MAPK/ERK2激活。此外，ZM 336372不会逆转Ras- 或Raf-转化细胞系的表现型。ZM 336372治疗诱导>100的c-Raf 和B-Raf亚型激活，但是它不会引起MKKI或p42 MAPK/ERKP激活，也不会诱导负载GTP的Ras增加，表明反馈控制环路通过Raf亚型抑制它们自身激活而存在，因此抑制作用总是被再活化而抵消。ZM 336372诱导的c-Raf活化不被MAPK级联激活，蛋白激酶C或磷脂酰肌醇3-激酶的抑制所阻断。ZM 336372 (1 μM)消除过氧化氢处理后eNOS的上调。 ZM 336372治疗，在良性肿瘤细胞中导致Raf-1，促分裂原活化蛋白激酶1/2，和细胞外信号调节激酶1/2连续磷酸化，并引起生物活性的激素水平，转录因子，和人无刚毛鳞甲同系物-1显著减少。此外，ZM 336372治疗显著抑制细胞增殖，并诱导细胞周期抑制剂p21和p18。 ZM 336372抑制嗜铬细胞瘤细胞的增殖，并抑制NE血管活性肽产生。 ZM 336372治疗，在HepG2中诱导剂量依赖性增殖抑制，激素分泌抑制，并上调细胞周期抑制剂。 在胰腺癌细胞系中，ZM 336372也会通过Ser 9上GSK-3β的磷酸化作用抑制糖原合成酶激酶-3β，从而诱导细胞凋亡。