KY19382 是一种有效的和具有口服活性的CXXC5-DVL和GSK3β的双重抑制剂，IC50值分别为 19 和 10 nM。KY19382 通过对 CXXC5-DVL 相互作用和 GSK3β 活性的抑制作用激活 Wnt/β-catenin 信号传导。KY19382 可用于高脂饮食 (HFD) 诱发的代谢性疾病的研究。
| 生物活性 | KY19382 is a potent and orally active dual inhibitor ofCXXC5-DVLandGSK3β, withIC50s of 19 and 10 nM, respectively. KY19382 activates Wnt/β-catenin signaling through inhibitory effects on both CXXC5-DVL interaction and GSK3β activity. KY19382 can be used for the research of high fat diet (HFD) induced metabolic diseases[1][2]. |
| IC50& Target[1] | CXXC5-DVL 19 nM (IC50) | GSK3β 10 nM (IC50) |
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体外研究
(In Vitro) | KY19382 (0.01 and 0.1 μM; 48 h) promotes ATDC5 cells proliferation[1].
KY19382 (0.1 μM; 3 d) up-regulates the mRNA levels of chondrogenic differentiation markers in ATDC5 and C28/I2 cells[1].
KY19382 (0.01 and 0.1 μM; 24 h) inactivates GSK3α/β in ATDC5 cells[1].
KY19382 (0.1 μM; 4 h) interrupts the CXXC5-DVL interaction in ATDC5 cells[1].
KY19382 (0.001-10 μM; 18 h) enhances the TOPFlash activity in HEK293 reporter cells[1].
KY19382 (0.1 μM; 48 h) elevates nuclear translocation of β-catenin in ATDC5 cells[1].
Cell Proliferation Assay[1] | Cell Line: | ATDC5 cells | | Concentration: | 0, 0.01, 0.1 μM | | Incubation Time: | 48 hours | | Result: | Enhanced the number of BrdU-positive ATDC5 cells. |
Cell Proliferation Assay[1] | Cell Line: | ATDC5 cells | | Concentration: | 0, 0.01, 0.1 μM | | Incubation Time: | 24 hours | | Result: | Increased the level of β-catenin in a dose-dependent manner. |
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体内研究
(In Vivo) | KY19382 (0.1 mg/kg; i.p. once daily for 2 weeks) delays growth plate senescence in older mice and promotes growth plate maturation in rapidly growing young mice[1].
KY19382 (0.1 mg/kg; i.p. once daily for 10 weeks) significantly increases the length of tibiae in mice[1].
KY19382 (5 mg/kg; i.p.) displays a relatively favorable bioavailability (F=16.74%), showing half-life of 16.20 h and an exposure level of 6,555.79 ngoh/ml[1].
KY19382 (A3051) (25 mg/kg; p.o. once daily for 16 weeks) shows reduction in adipocyte size and anti-inflammatory effects[2].
A3051 (25 mg/kg; p.o. once daily for 5 days) reduces fasting glucose in mice[2].
A3051 (25 mg/kg; p.o. once daily for 3 weeks) reduces the hepatosteatosis in mice[2].
| Animal Model: | C57BL/6 male mice (7-weeks-old or 3-weeks-old)[1] | | Dosage: | 0.1 mg/kg | | Administration: | I.p. once daily for 2 weeks | | Result: | Increased nuclear β-catenin in the growth plate chondrocytes dramatically.
Elevated the height of each growth plate zone and BrdU-positive cells.
Did not affect the cartilage resorption of rapidly growing young mice. |
| Animal Model: | SD male rats[1] | | Dosage: | 1 mg/kg for i.v. and 5 mg/kg for i.p. (Pharmacokinetic Analysis) | | Administration: | I.v. and i.p. administration | | Result: | I.v.: t1/2=3.33 h; AUC=7832.81 ng·h/mL; CL=0.12 L/h/kg.
I.p.: t1/2=16.20 h; F=16.74%; Cmax=463.37 ng/mL. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 5 mg/mL(13.88 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.7763 mL | 13.8816 mL | 27.7631 mL | | 5 mM | 0.5553 mL | 2.7763 mL | 5.5526 mL | | 10 mM | 0.2776 mL | 1.3882 mL | 2.7763 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 |
