1-Naphthohydroxamic acid

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

1-NaphthoHydroxamic Acid (Compound 2) 是一种有效的选择性 HDAC8 抑制剂，IC50 为 14 μM，它对 HDAC8 的选择性比 I 类 HDAC1 和 II 类 HDAC6 更高 (IC50 >100 μM)。

1-Naphthohydroxamic acid (Compound 2) is a potent and selective HDAC8 inhibitor with an IC50 of 14 μM, and it is more selectively for HDAC8 than class I HDAC1 and class II HDAC6 (IC50 >100 μM). 1-Naphthohydroxamic acid does not increase global histone H4 acetylation and also does not reduce total intracellular HDAC activity, But it can induce tubulin acetylation. 1-Naphthohydroxamic acid (compound 2; 20-40 μM; 0-144 ?hours; BE(2)-C, SK-N-BE(2) and SH-SY5Y cells) treatment reduces cell numbers in a concentration-dependent manner. 1-Naphthohydroxamic acid reduces the formation of clones in soft-agar concentration dependently.. When either cell type (HeLa and HEK293 cells) is treated with 1-Naphthohydroxamic acid (compound 2; 0.8 μM, 4 μM, 20 μM or 100 μM), only tubulin becomes hyperacetylated[1]. 1-Naphthohydroxamic acid (compound 2) at concentrations in the range of its in vitro IC50 against HDAC8 results in reduced cell density and outgrowth of neurite-like structures that stained positive for neurofilament.1-Naphthohydroxamic acid has the maximum tolerable doses at 50?mg/kg per day. At these concentrations, neither body weight nor blood parameters are critically changed[3]. Dose-limiting toxicities (DLTs) of 1-Naphthohydroxamic acid (compound 2; 0-40 mg/kg; intraperitoneal injection; daily; for 10 day; NMRI Foxn1 nude mice) include weight loss and signs of liver toxicity, as evidenced by elevated plasma liver enzymes and detection of necrotic areas on histological liver examination. Pharmacokinetic studies after intraperitoneal administration of the inhibitors identified the half-life of 1-Naphthohydroxamic acid to be ~15?min, with a plasma peak concentration of ~30?μM.

1-Naphthohydroxamic acid (compound 2; 20-40 μM; 0-144 ?hours; BE(2)-C, SK-N-BE(2) and SH-SY5Y cells) treatment reduces cell numbers in a concentration-dependent manner.1-Naphthohydroxamic acid (compound 2) at concentrations in the range of its in vitro IC50 against HDAC8 results in reduced cell density and outgrowth of neurite-like structures that stained positive for neurofilament.1-Naphthohydroxamic acid reduces the formation of clones in soft-agar concentration dependently.When either cell type (HeLa and HEK293 cells) is treated with 1-Naphthohydroxamic acid (compound 2; 0.8 μM, 4 μM, 20 μM or 100 μM), only tubulin becomes hyperacetylated. Cell Proliferation Assay Cell Line:BE(2)-C, SK-N-BE(2) and SH-SY5Y cells Concentration:20 μM, 40 μM Incubation Time:0?hours, 24?hours, 48?hours, 72?hours, 96?hours, and 144 ?hours Result:Reduced cell numbers in a concentration-dependent manner.

Dose-limiting toxicities (DLTs) of 1-Naphthohydroxamic acid (compound 2; 0-40 mg/kg; intraperitoneal injection; daily; for 10 day; NMRI Foxn1 nude mice) include weight loss and signs of liver toxicity, as evidenced by elevated plasma liver enzymes and detection of necrotic areas on histological liver examination. 1-Naphthohydroxamic acid has the maximum tolerable doses at 50?mg/kg per day. At these concentrations, neither body weight nor blood parameters are critically changed. Pharmacokinetic studies after intraperitoneal administration of the inhibitors identified the half-life of 1-Naphthohydroxamic acid to be ~15?min, with a plasma peak concentration of ~30?μM. Animal Model:NMRI Foxn1 nude mice Dosage:0 mg/kg, 50 mg/kg, 100mg/kg, 200 mg/kg, 300 mg/kg 400 mg/kg Administration:Intraperitoneal injection; daily; for 10 days Result:Dose-limiting toxicities (DLTs) included weight loss and signs of liver toxicity, as evidenced by elevated plasma liver enzymes and detection of necrotic areas on histological liver examination.

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Cell Cycle/DNA Damage

HDAC

HDAC8|HDAC1|HDAC6

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6953-61-3

187.19

C11H9NO2

>98% (HPLC)

DMSO:125 mg/mL (667.77 mM; Need ultrasonic)

ONC(=O)C1=CC=CC2=CC=CC=C12

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(-20℃)

With Ice Pack

≥ 2 years