1-Naphthohydroxamic acid

Names

[ Name ]:
1-Naphthohydroxamic acid

[Synonym ]:
1-NAPHTHALENECARBOXAMIDE,N-HYDROXY
a-Naphthohydroxamic acid
N-hydroxynaphthalene-1-carboxamide
1-Naphthalenecarboxamide, N-hydroxy-
N-Hydroxy-1-naphthamide
1-naphthohydroxamic acid

Biological Activity

[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].

[Related Catalog]:

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> HDAC

Signaling Pathways >> Epigenetics >> HDAC

[Target]

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.

[References]

[1]. Krennhrubec K, et al. Design and evaluation of 'Linkerless' hydroxamic acids as selective HDAC8 inhibitors. Bioorg Med Chem Lett. 2007 May 15;17(10):2874-8.

[2]. Oehme I, et al. Histone deacetylase 8 in neuroblastoma tumorigenesis. Clin Cancer Res. 2009 Jan 1;15(1):91-9.

Chemical & Physical Properties

[ Density]:
1.3±0.1 g/cm3

[ Molecular Formula ]:
C₁₁H₉NO₂

[ Molecular Weight ]:
187.195

[ Exact Mass ]:
187.063324

[ PSA ]:
49.33000

[ LogP ]:
1.49

[ Appearance of Characters ]:
white to tan

[ Index of Refraction ]:
1.678

[ Storage condition ]:
2-8°C

[ Water Solubility ]:
DMSO: ≥5mg/mL

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: QJ1894500

CHEMICAL NAME :: 1-Naphthalenecarboxamide, N-hydroxy-

CAS REGISTRY NUMBER :: 6953-61-3

BEILSTEIN REFERENCE NO. :: 2094470

LAST UPDATED :: 199612

DATA ITEMS CITED :: 1

MOLECULAR FORMULA :: C11-H9-N-O2

MOLECULAR WEIGHT :: 187.21

WISWESSER LINE NOTATION :: L66J BVMQ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

MUTATION DATA

TYPE OF TEST :: Mutation in microorganisms

TEST SYSTEM :: Bacteria - Salmonella typhimurium

DOSE/DURATION :: 2500 nmol/plate

REFERENCE :: MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 135,139,1984

Safety Information

[ Risk Phrases ]:
52

[ RIDADR ]:
NONH for all modes of transport

[ RTECS ]:
QJ1894500

[ HS Code ]:
2924299090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2924299090

[ Summary ]:
2924299090. other cyclic amides (including cyclic carbamates) and their derivatives; salts thereof. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:30.0%