中文名称:

3-[3-[2-(1-哌啶基)乙氧基]苯基]-5-(1H-1,2,4-三唑-5-基)-1H-吲唑盐酸盐

中文同义词:

3-[3-[2-(1-哌啶基)乙氧基]苯基]-5-(1H-1,2,4-三唑-5-基)-1H-吲唑盐酸盐;JNK抑制剂(CC-401 HYDROCHLORIDE);CC-401盐酸盐;化合物CC-401 HYDROCHLORIDE

英文名称:

CC401 HCl

英文同义词:

CC-401 (hydrochloride);3-[3-[2-(1-Piperidinyl)ethoxy]phenyl]-5-(1H-1,2,4-triazol-5-yl)-1H-indazole hydrochloride (1:1);CC 401 HYDROCHLORIDE; CC401 HYDROCHLORIDE; CC401 HCL;CC-401 dihydrochloride >=95% (HPLC)

CAS号:

1438391-30-0

分子式:

C22H25ClN6O

分子量:

424.9265

EINECS号:

相关类别:

细胞生物学试剂;API

Mol文件:

1438391-30-0.mol

形态

White powder.

生物活性

CC-401是有效的JNK抑制剂，其对JNK的选择性是对其他相关性激酶的选择性的至少40倍。

靶点

JNK 25-50 nM (Ki)

JNK 25-50 nM (Ki)

体外研究

CC-401 has at least 40-fold selectivity for JNK compared with other related kinases, including p38, extracellular signal-regulated kinase (ERK), inhibitor of κB kinase (IKK2), protein kinase C, Lck, zeta-associated protein of 70 kDa (ZAP70). In cell-based assays, 1 to 5 μM CC-401 provides specific JNK inhibition. CC-401, a small molecule that is a specific inhibitor of all three JNK isoforms. CC-401 competitively binds the ATP binding site in JNK, resulting in inhibition of the phosphorylation of the N-terminal activation domain of the transcription factor c-Jun. The specificity of this inhibitor is tested in vitro using osmotic stress of the HK-2 human tubular epithelial cell line. CC-401 inhibits sorbitol-induced phosphorylation of c-Jun in a dosage-dependent manner. However, CC-401 does not prevent sorbitol-induced phosphorylation of JNK, p38, or ERK.

体内研究

The staining of p-JNK is moderately induced in bevazicumab and Oxaliplatin treatments as compared to control, and in the CC-401-treated samples p-cJun content is significantly lower, consistent with effective JNK inhibition. DNA damage is modestly elevated in combined treatments with CC-401. CC-401 treatment from days 7 to 24 slows the progression of proteinuria, which is significantly reduced compared to the no-treatment and vehicle groups at days 14 and 21. However, there is still an increase in the degree of proteinuria at day 21 in CC-401-treated rats compared to proteinuria at day 5. The vehicle and no-treatment groups developed renal impairment at day 24 as shown by an increase in serum creatinine. This is prevented by CC-401 treatment.