KY19382

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

KY19382 是一种有效的口服活性 CXXC5-DVL 和 GSK3β 双重抑制剂（IC50 分别为 19 和 10 nM）。

KY19382 is a potent and orally active dual inhibitor of CXXC5-DVL and GSK3β( IC50s of 19 and 10 nM, respectively). It?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.

KY19382 (0.01 and 0.1 μM; 48 h) promotes ATDC5 cells proliferation.KY19382 (0.1 μM; 3 d) up-regulates the mRNA levels of chondrogenic differentiation markers in ATDC5 and C28/I2 cells.KY19382 (0.01 and 0.1 μM; 24 h) inactivates GSK3α/β in ATDC5 cells.KY19382 (0.1 μM; 4 h) interrupts the CXXC5-DVL interaction in ATDC5 cells.KY19382 (0.001-10 μM; 18 h) enhances the TOPFlash activity in HEK293 reporter cells.KY19382 (0.1 μM; 48 h) elevates nuclear translocation of β-catenin in ATDC5 cells.Cell Proliferation Assay 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 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.

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.KY19382 (0.1 mg/kg; i.p. once daily for 10 weeks) significantly increases the length of tibiae in mice.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 ng?h/ml.KY19382 (A3051) (25 mg/kg; p.o. once daily for 16 weeks) shows reduction in adipocyte size and anti-inflammatory effects.A3051 (25 mg/kg; p.o. once daily for 5 days) reduces fasting glucose in mice.A3051 (25 mg/kg; p.o. once daily for 3 weeks) reduces the hepatosteatosis in mice. Animal Model:C57BL/6 male mice (7-weeks-old or 3-weeks-old) 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 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.

2H-Indol-2-one, 5,6-dichloro-3-[1,3-dihydro-3-(methoxyimino)-2H-indol-2-ylidene]-1,3-dihydro-Ky19382 | A3051

PI3K/Akt/mTOR signaling

GSK-3

CXXC5-DVL|GSK-3β

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2226664-93-1

360.2

C17H11Cl2N3O2

>98% (HPLC)

DMSO:5 mg/mL (13.88 mM; Need ultrasonic)

CO/N=C\1/C2=CC=CC=C2N=C1C3=C(NC4=CC(=C(C=C43)Cl)Cl)O

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(-20℃)

With Ice Pack

≥ 2 years