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VER-155008

CAS No. : 1134156-31-2

產品活性：VER-155008 is an inhibitor of Hsp70, with IC₅₀s of 0.5 μM, 2.6 μM, and 2.6 μM for Hsp70, Hsc70 and Grp7, respectively, and with a K_d of 0.3 μM for Hsp70.

研究領域：Cell Cycle/DNA Damage  |  Metabolic Enzyme/Protease  |  Autophagy

作用靶點：HSP  |  Autophagy

In Vitro: VER-155008 is an inhibitor of Hsc70 and Hsp70, with IC₅₀s of 0.5 μM, 2.6 μM, and 2.6 μM for Hsp70, Hsc70 and Grp7, respectively, a with a K_d of 0.3 μM for Hsp70, but shows no activities against Hsp90, with an IC₅₀ of >200 μM. VER-155008 inhibits the proliferation of a variety of human colon and breast tumor cell lines, such as BT474, MB-468, HCT116 and HT29 cells, with GI₅₀s of 10.4 μM, 14.4 μM, 5.3 μM, and 12.8 μM, respectively. VER-155008 (5-40 μM) induces client protein degradation in HCT116 and BT474 carcinoma cells. VER-155008 also induces apoptosis in human tumor cell lines. VER-155008 (0.05-5 μM) reverses Aβ-induced axonal degeneration in cultured neurons. VER-155008 (10 μM or 25 μM) inhibits Hsp70 and suppresses the proliferation of LNCaP95 cells. VER-155008 also reduces full-length androgen receptor (AR-FL) and androgen receptor splice variant 7 (AR-V7) protein expression.

In Vivo: VER-155008 (25 mg/kg, i.v.) exhibits plasma clearance in naive female BALB/c mice. VER-155008 (40 mg/kg, i.v.) also shows rapid plasma clearance, and reduces the tumor levels in the HCT116 tumor bearing nude BALB/c mice. VER-155008 (10 μmol/kg/day, i.p.) rescues memory deficits, and reduces axonal swelling associated with amyloid plaques in 5XFAD mice. VER-155008 (89.9 μmol/kg/day, i.p.) penetrates into the brain after administration in 5XFAD mice. VER-155008 also decreases amyloid plaques and PHF-tau associated with amyloid plaques in 5XFAD mice.

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