202475-60-3
基本信息
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%
Janex 1
WHI-P131
WHI-P131, >98%
JAK3 INHIBITOR I
JANEX-1
WHI-P131
WHI-P131(Janex 1)
A JAK3 inhibitor WHI-P131
WHIP-131
JANEX-1)
WHIP131
JANEX1
4-(6,7-dimethoxyquinazolin-4-ylamino)phenol
物理化学性质
| 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 |
| 酸度系数(pKa) | 10.06±0.26(Predicted) |
| 形态 | solid |
| 颜色 | yellow |
| 稳定性 | Stable for 2 years from date of purchase as supplied. Protect from moisture. Solutions in DMSO may be stored at -20°C for up to 2 months. |
安全数据
| 危险性符号(GHS) |  GHS07 |
| 警示词 | 警告 |
| 危险性描述 | H302-H315-H319-H335 |
| 防范说明 | P261-P305+P351+P338 |
| 危险品标志 | Xi |
| 危险类别码 | 36/37/38 |
| 安全说明 | 26-36 |
| WGK Germany | 3 |
常见问题列表
| Target | Value |
|
JAK3
(Cell-free assay) | 78 μM |
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.
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).