JH-XVII-10 是一种有效的，具有选择性和口服活性的DYRK1A和DYRK1B抑制剂，IC50值分别为 3 nM 和 5 nM。JH-XVII-10 在颈部鳞状细胞癌 (HNSCC) 细胞系中显示出抗肿瘤功效。
产品描述
JH-XVII-10 is a potent, selective and orally active DYRK1A and DYRK1B inhibitor with IC 50 s of 3 nM and 5 nM for DYRK1A and DYRK1B, respectively. JH-XVII-10 shows antitumor efficacy in neck squamous cell carcinoma (HNSCC) cell lines [1].
体外活性
JH-XVII-10 (compound 10) (1 μM; CAL27 cells) shows active against JNK1 (IC 50 =1130 nM), JNK2 (IC 50 =1100 nM), JNK3 (IC 50 =>10 000 nM), FAK (IC 50 =90 nM), RSK1 (IC 50 =82 nM), RSK2 (IC 50 =80 nM), RSK3 (IC 50 =61 nM) [1]. JH-XVII-10 (10 μM; 72 h) decreases cell proliferation by ~45%, and ~40% for CAL27 and FaDu cells, respectively [1]. JH-XVII-10 (1, 10 μM; 24 h) induces apoptosis in CAL27 cells [1]. JH-XVII-10 (0.5, 1, 5, 10 μM; 24 h) shows inhibitory effects on pro-tumor signaling in CAL27 cells [1]. Cell Proliferation Assay [1] Cell Line: CAL27, FaDu, HEK293FT cells Concentration: 10 μM Incubation Time: 72 h Result: Decreased cell proliferation by ~45%, and ~40% for CAL27 and FaDu cells, respectively. Western Blot Analysis [1] Cell Line: CAL27 cells Concentration: 0.5, 1, 5, 10 μM Incubation Time: 24 h Result: Showed inhibitory effects on pro-tumor signaling. Apoptosis Analysis [1] Cell Line: CAL27 cells Concentration: 1, 10 μM Incubation Time: 24 h Result: Induced increases in the proapoptotic marker (cleaved PARP), and decreased the expression of antiapoptotic protein BCL-xL.
体内活性
JH-XVII-10 (2 mg/kg, i.v.; 10 mg/kg, p.o.) shows oral bioavailability (F=12%) [1]. Pharmacokinetic Parameters of JH-XVII-10 in C57Bl/6 male mice [1]. administration parameters rat dog i.v. T 1/2 (h) 1.4±0.3 5.70±1.2 AUC 0-∞ (ng*h/mL) 931.3±95.7 14,830.8±5475.4 CL (mL/min/kg) 17.6±2.0 149.9±62.5 V ss (L/kg) 1.7±0.2 828.7±134.2 p.o. C max (ng/mL) 1661.1±916.6 3979.4±483.5 T max (h) 0.9±0.8 1.3±0.5 T 1/2 (h) 1.4±0.2 4.9±0.6 AUC 0-∞ (ng*h/mL) 5044.9±1061 23,109.9±7752.2 F (%) 54.2 31.8 C57Bl/6 male mice; 2 mg/kg, i.v.; 10 mg/kg, p.o. [1] Animal Model: C57Bl/6 male mice [1] Dosage: Administration: 2 mg/kg, i.v.; 10 mg/kg, p.o. Result: Showed oral bioavailability (F=12%).
分子式
C21H16F4N8O
分子量
472.4
储存和溶解度
(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years
