Naphthol AS-E

Names

[ CAS No. ]:
92-78-4

[ Name ]:
Naphthol AS-E

[Synonym ]:
MFCD00021639
Amanil Naphthol AS-E
Cibanaphthol RC
3-hydroxy-naphthalene-2-carboxylic acid 4-chloro-anilide
3-Hydroxy-[2]naphthoesaeure-(4-chlor-anilid)
naphthol AS-E
EINECS 202-189-7
Naphtoelan E
Naphtazol E
Naphtanilide E
4'-Chloro-3-hydroxy-2-naphthanilide
Sanatol E
3-hydroxy-[2]naphthoic acid-(4-chloro-anilide)
Daito Grounder E

Biological Activity

[Description]:

Naphthol AS-E is a potent and cell-permeable inhibitor of KIX-KID interaction. Naphthol AS-E directly binds to the KIX domain of CBP (Kd:8.6 µM), blocks the interaction between the KIX domain and the KID domain of CREB with IC50 of 2.26 µM. Naphthol AS-E can be used for cancer research.

[Related Catalog]:

Research Areas >> Cancer

Signaling Pathways >> Epigenetics >> Histone Acetyltransferase

Signaling Pathways >> Epigenetics >> Epigenetic Reader Domain

[Target]

KIX-KID:2.26 μM (IC50)

[In Vitro]

CREB (cyclic AMP-response element-binding protein) is a downstream transcription factor of a multitude of signaling pathways emanating from receptor tyrosine kinases or G-protein coupled receptors. CREB can not be activated until it is phosphorylated at Ser133 and its subsequent binding to CREB-binding protein (CBP) through the kinase-inducible domain (KID) in CREB and KID-interacting (KIX) domain in CBP. In a cell-based CREB Renilla luciferase reporter assay, Naphthol AS-E inhibits CREB-mediated gene transcription with an IC50 of 2.29 µM. In HEK293T-based complementation assay, Naphthol AS-E dose-dependently inhibited Renilla luciferase activity with an IC50 of 2.9 µM by directly binding to CBP's KIX domain (Kd ~8.6 µM using a recombinant KIX). Naphthol AS-E exhibits low µM activity in inhibiting the proliferation of all these cancer cells, which is consistent with its cellular CREB inhibition potency. The average GI50 values for A549, MCF-7, MDA-MB-231 and MDA-MB-468 are approximately 2.9µM, 2.81µM, 2.35µM and 1.46µM, respectively. Naphthol AS-E (2.5 µM-10 µM; 48 hours) decreases the expression of anti-apoptotic protein Bcl-2. The expression of VEGF is also decreased.

[References]

[1]. Fuchun Xie, et al. Synthesis and Evaluation of an O-Aminated Naphthol AS-E as a Prodrug of CREB-mediated Gene Transcription Inhibition. Lett Org Chem. 2013 Jun;10(5):380-384.

[2]. Bingbing X Li, et al. Discovery of a small-molecule inhibitor of the KIX-KID interaction. Chembiochem. 2009 Nov 23;10(17):2721-4.

Chemical & Physical Properties

[ Density]:
1.399 g/cm3

[ Boiling Point ]:
416.5ºC at 760 mmHg

[ Melting Point ]:
255°C

[ Molecular Formula ]:
C₁₇H₁₂ClNO₂

[ Molecular Weight ]:
297.73600

[ Flash Point ]:
205.7ºC

[ Exact Mass ]:
297.05600

[ PSA ]:
49.33000

[ LogP ]:
4.52410

[ Index of Refraction ]:
1.735

MSDS

Click to get detail MSDS

Safety Information

[ Hazard Codes ]:
Xn

[ Risk Phrases ]:
R42/43:May cause sensitization by inhalation and skin contact .

[ Safety Phrases ]:
S7-S36-S24/25

[ WGK Germany ]:
3

[ RTECS ]:
MR0176000

[ HS Code ]:
29053980

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%