4-(4-羟基苯基)氨基-6,7-二甲氧基喹唑啉
中文名称:
4-(4-羟基苯基)氨基-6,7-二甲氧基喹唑啉
中文同义词:
4-(4-羟基苯基)氨基-6,7-二甲氧基喹唑啉;4-(4-羟基苯基)氨基-6,7-二甲氧基喹唑啉, >98%;JAK3抑制剂(JANEX-1)
英文名称:
JAK3 INHIBITOR I
英文同义词:
4-(4-HYDROXYPHENYL)AMINO-6,7-DIMETHOXYQUINAZOLINE;JAK3 INHIBITOR I;WHI-P131;Janex 1;A JAK3 inhibitor WHI-P131;4-(6,7-dimethoxyquinazolin-4-ylamino)phenol;WHI-P131(Janex 1);JANEX-1;WHI-P131
CAS号:
202475-60-3
分子式:
C16H15N3O3
分子量:
297.31
EINECS号:
相关类别:
小分子抑制剂;小分子抑制剂，天然产物;细胞生物学试剂;Inhibitors;Heterocycles, Inhibitors, Pharmaceuticals, Intermediates Fine Chemicals
Mol文件:
202475-60-3.mol
沸点
468.1±40.0 °C(Predicted)
密度
1.336±0.06 g/cm3(Predicted)
储存条件
Keep in dark place,Inert atmosphere,2-8°C
溶解度
DMSO: 18 mg/mL, soluble
形态
solid
酸度系数(pKa)
10.06±0.26(Predicted)
颜色
yellow
生物活性
JANEX-1 (WHI-P131)是JAK3小分子抑制剂，选择性抑制JAK3，IC50为78 μM。它不影响JAK1或JAK2，及其他蛋白酪氨酸激酶的活性（IC50 ≥ 350 µM）。
靶点
Target Value
JAK3
(Cell-free assay) 78 μM
Target
Value
JAK3
(Cell-free assay)
78 μM
体外研究
JANEX-1 (WHI-P131) shows potent JAK3-inhibitory activity (IC 50 of 78 μM), does not inhibit JAK1 and JAK2, the ZAP/SYK family tyrosine kinase SYK, the TEC family tyrosine kinase BTK, the SRC family tyrosine kinase LYN, or the receptor family tyrosine kinase insulin receptor kinase, even at concentrations as high as 350 μM. JANEX-1 induces apoptosis in JAK3-expressing human leukemia cell lines NALM-6 and LC1;19 but not in melanoma (M24-MET) or squamous carcinoma (SQ20B) cells. WHI-P131 inhibits the clonogenic growth of JAK3-positive leukemia cell lines DAUDI, RAMOS, LC1;19, NALM-6, MOLT-3, and HL-60 (but not JAK3-negative BT-20 breast cancer, M24-MET melanoma, or SQ20B squamous carcinoma cell lines) in a concentration-dependent fashion. WHI-P131 inhibits clonogenic growth in a concentration-dependent fashion with EC 50 s of 24.4 μM for NALM-6 cells and 18.8 μM for DAUDI cells. At 100 μM, WHI-P131 inhibits the in vitro colony formation by these leukemia cell lines by >99%. In contrast, JANEX-1 does not inhibit the clonogenic growth of JAK3-negative M24-MET melanoma or SQ20B squamous carcinoma cell lines.
体内研究
JANEX-1 is administered at doses ranging from 5 to 100 mg/kg. Evaluation of CPK activity revealed a dose-response curve with an effective dose 50 (ED 50 ) value of 7.44 mg/kg. Mice receiving JANEX-1 displayed significantly reduced CPK and LDH levels. In addition, the infarct size of JANEX-1-treated mice (30.16±2.79%) is significantly decreased when compared with I/R-operated mice (65.64±3.76%). JANEX-1 (WHI-P131) is absorbed rapidly, and the time to reach the maximum plasma JANEX-1 concentration (t max ) is 24.7±1.7 min. JANEX-1 is rapidly eliminated with an elimination half-life of 45.6±5.5 min. Although the predicted maximum plasma JANEX-1 concentration is 10.5 ± 0.8 μM, which is only half of the C max following i.v. administration of the same bolus dose, the i.p. bioavailability is 94.6% and the systemic exposure levels (i.e., AUC) are very similar to those observed after i.v. injection (17.1±2.2 μM•h versus 18.1±1.2 μM•h).
危险品标志
Xi
危险类别码
36/37/38
安全说明
26-36
WGK Germany
3
