KY19382 (Synonyms: A3051)

KY19382 is a potent and orally active dual inhibitor of CXXC5-DVL and GSK3β, with IC50s 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].

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

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 ng•h/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]

[1]. Choi S, et, al. CXXC5 mediates growth plate senescence and is a target for enhancement of longitudinal bone growth. Life Sci Alliance. 2019 Apr 10; 2(2): e201800254. [2]. Choi KY, et, al. Compositions and methods for suppressing and/or treating metabolic diseases and/or a clinical condition thereof. WO2020079569.