KY19382

SKU: orb1218409

Description

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.

Key Properties

• CAS Number: 2226664-93-1
• MW: 360.2
• Purity: >98% (HPLC)
• Formula: C₁₇H₁₁Cl₂N₃O₂
• SMILES: CO/N=C\1/C2=CC=CC=C2N=C1C3=C(NC4=CC(=C(C=C43)Cl)Cl)O
• Target: GSK-3
• Solubility: DMSO:5 mg/mL (13.88 mM; Need ultrasonic)

Bioactivity

• 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. 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.
  Read more...
• In Vitro:
  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.
  Read more...

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

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

Quick Database Links

Gene Symbol

GSK-3