JANEX-1

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JANEX-1

本产品不向个人销售，仅用作科学研究，不用于任何人体实验及非科研性质的动物实验。

CAS NO:	202475-60-3
规格:	≥98%

包装与价格：

包装	价格(元)
5mg	电议
10mg	电议
25mg	电议
50mg	电议
100mg	电议
250mg	电议
500mg	电议

产品介绍

JANEX-1 (aslo known as WHI-P131) is a novel, potent and selective inhibitor of the Janus kinase 3 (JAK3) that selectively inhibits JAK3 with an IC50 of 78 μM and does not inhibit JAK1 and JAK2. It triggers apoptosis in human acute lymphoblastic leukemia (ALL) cells. Following i.v. administration, the terminal elimination half-life of WHI-P131 was 73.2 min in rats, 103.4 min in mice, and 45.0 min in monkeys. The i.v. administered WHI-P131 showed a very wide tissue distribution in mice. Following i.p. administration, WHI-P131 was rapidly absorbed in both rats and mice, and the time to reach the maximum plasma concentration (tmax) was 24.8 min in rats and 10.0 min in mice.

理化性质和储存条件

Molecular Weight (MW)	297.31
Formula	C16H15N3O3
CAS No.	202475-60-3
Storage	-20℃ for 3 years in powder form
Storage	-80℃ for 2 years in solvent
Solubility (In vitro)	DMSO: ≥ 5 mg/mL
	Water: <1 mg/mL
	Ethanol:<1 mg/mL
Chemical Name	4-[(6,7-dimethoxy-4-quinazolinyl)amino]-phenol
Synonyms	WHI-P131; WHI P-131; WHI P131; JANEX-1; JANEX 1; JANEX1

实验参考方法

In Vitro	In vitro activity: JANEX-1 (WHI-P131) shows potent JAK3-inhibitory activity (IC50 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 EC50s 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. Kinase Assay: JANEX-1 inhibits JAK3 but not JAK1 or JAK2. The ZAP/SYK family tyrosine kinase SYK, TEC family tyrosine kinase Bruton’s tyrosine kinase (BTK), SRC family tyrosine kinase LYN, and receptor family tyrosine kinase insulin receptor kinase (IRK) are not inhibited by JANEX-1. JANEX-1 suppresses IL-1β and IFN-γ-induced phosphorylation of STAT-1, STAT-3, and STAT-5 proteins. JANEX-1 has a potent inhibitory effect on cytokine-induced β-cell damage. Cell Assay: The following cell lines are used in various biological assays: NALM-6 (pre-B-ALL), LC1;19 (pre-B-ALL), DAUDI (B-ALL), RAMOS (B-ALL), MOLT-3 (T-cell ALL), HL60 (acute myelogenous leukemia), BT-20 (breast cancer), M24-MET (melanoma), SQ20B (squamous cell carcinoma), and PC3 (prostate cancer). These cell lines are maintained in culture. Cells are seeded in six-well tissue culture plates at a density of 50×104 cells/well in a treatment medium containing various concentrations of JANEX-1 (0.1, 0.2, 0.3, 0.4 and 0.5 nM) and incubated for 24-48 h at 37°C in a humidified 5% CO2 atmosphere. Cells are examined for apoptotic changes after treatment with JANEX-1 by the in situ TdT-mediated dUTP end-labeling assay using the ApopTag apoptosis detection kit.
In Vivo	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 (ED50) 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 (tmax) 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 Cmax 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 μMoh versus 18.1±1.2 μMoh).
Animal model	Female NOD mice
Formulation & Dosage	Dissolved in DMSO in PBS; 20, 50 and 100 mg/kg/day; i.p.
References	Clin Immunol. 2003, 106(3):213-25.; Exp Cell Res. 2009, 315(12):2064-71.