1. Cell Cycle/DNA Damage
    Epigenetics
  2. HDAC
  3. 1-Naphthohydroxamic acid

1-Naphthohydroxamic acid 

目录号: HY-130538 纯度: >98.0%
产品使用指南

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。

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1-Naphthohydroxamic acid Chemical Structure

1-Naphthohydroxamic acid Chemical Structure

CAS No. : 6953-61-3

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Description

1-Naphthohydroxamic acid (Compound 2) is a potent and selective HDAC8 inhibitor with an IC50 of 14 μM. 1-Naphthohydroxamic acid 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[1][2].1-Naphthohydroxamic acid can induce tubulin acetylation[3].

IC50 & Target[1]

HDAC8

14 μM (IC50)

HDAC1

>100 μM (IC50)

HDAC6

>100 μM (IC50)

In Vitro

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[2].
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[2].
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].

Cell Proliferation Assay[2]

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.
In Vivo

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[3].
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[3].

Animal Model: NMRI Foxn1 nude mice[3]
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.
Molecular Weight

187.19

Formula

C₁₁H₉NO₂

CAS No.

6953-61-3

SMILES

O=C(C1=C2C=CC=CC2=CC=C1)NO

Shipping

Room temperature in continental US; may vary elsewhere.

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Solvent & Solubility
In Vitro: 

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

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 5.3422 mL 26.7108 mL 53.4217 mL
5 mM 1.0684 mL 5.3422 mL 10.6843 mL
10 mM 0.5342 mL 2.6711 mL 5.3422 mL
*

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储备液的保存方式和期限:-80°C, 6 months; -20°C, 1 month。 -80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。

References
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Keywords:

1-Naphthohydroxamic acidHDACHistone deacetylasesHDAC8tubulinhyperacetylateddeacetylateanti-proliferationcloneacetylationInhibitorinhibitorinhibit

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