1-萘羟肟酸

生物活性靶点体外研究体内研究 1-萘羟肟酸试剂级价格

1-萘羟肟酸

CAS号:6953-61-3
英文名:1-NAPHTHOHYDROXAMIC ACID
中文名:1-萘羟肟酸
CBNumber:CB2462406
分子式:C11H9NO2
分子量:187.19
MOL File:6953-61-3.mol

1-萘羟肟酸化学性质

熔点 :176-178 °C
密度 :1.291±0.06 g/cm3(Predicted)
储存条件 :2-8°C
溶解度 :DMSO: ≥5mg/mL
形态 :White solid
酸度系数(pKa) :8.91±0.30(Predicted)
颜色 :white to tan

安全信息

危险类别码 :52
WGK Germany :3
RTECS号 :QJ1894500
海关编码 :2928009090

1-萘羟肟酸性质、用途与生产工艺

生物活性 1-Naphthohydroxamic acid (Compound 2) 是一种有效的，选择性的 HDAC8 抑制剂，IC50 为 14 μM。1-Naphthohydroxamic acid 对 HDAC8 的选择性高于 I 类 HDAC1 和 II 类 HDAC6 (IC50 >100 μM)。1-Naphthohydroxamic acid 不会增加整体组蛋白 H4 的乙酰化，也不会降低总细胞内 HDAC 的活性。1-Naphthohydroxamic acid 可诱导微管蛋白乙酰化。

靶点

HDAC8

14 μM (IC ₅₀ )

HDAC1

>100 μM (IC ₅₀ )

HDAC6

>100 μM (IC ₅₀ )

体外研究

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 IC ₅₀ 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.

体内研究

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.