CGP 52411

Names

[ Name ]:
CGP 52411

[Synonym ]:
5,6-bis-phenylamino-isoindole-1,3-dione
DAPH-1
4,5-dianilinophthalimide
DAPH
5,6-bis-phenylamino-isoindole-1,3-dione,DAPH

Biological Activity

[Description]:

CGP52411 (DAPH) is a high selective, potent, orally active and ATP-competitive EGFR inhibitor with an IC50 of 0.3 μM. CGP52411 blocks the toxic influx of Ca2+ ions into neuronal cells, and dramatic inhibits and reverses the formation of β-amyloid (Aβ42) fibril aggregates associated with Alzheimer's disease[1][2].

[Related Catalog]:

Research Areas >> Cancer

Signaling Pathways >> JAK/STAT Signaling >> EGFR

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> EGFR

Research Areas >> Neurological Disease

[Target]

EGFR:0.3 μM (IC50)

Amyloid-β

[In Vitro]

CGP52411 (DAPH; 0-100 μM; 90 minutes; A431 cells) treatment inhibits autophosphorylation and c-src autophosphorylation in vitro in a dose-dependent manner with IC50s of 1 μM and 16 μM, respectively. CGP52411 treatment also shows a concentration-dependent reduction in tyrosine phosphorylation of p185c-erbB2 with an IC50 value of 10 μM[1]. CGP52411 (DAPH) inhibits c-src kinase with an IC50 value of 16 μM. CGP52411 inhibits PKC isozymes isolated from porcine brain with an IC50 of 80 μM. CGP52411 inhibits conventional PKC isozymes (cPKCs α, β-1, β-2, and γ) but not nonconventional PKC isozymes (nPKCs δ, ε, and ζ) or atypical PKC isozymes (aPKC η)[1]. Western Blot Analysis[1] Cell Line: A431 cells Concentration: 0 μM, 0.1 μM, 1 μM, 10 μM, 50 μM, 100 μM Incubation Time: 90 minutes Result: Inhibited autophosphorylation in vitro in a dose-dependent manner with an IC50 of 1 μM. c-src autophosphorylation was inhibited with an IC50 of 16 μM. And also resulted in a concentration-dependent reduction in tyrosine phosphorylation of p185c-erbB2, with an estimated IC50 value of 10 μM.

[In Vivo]

CGP52411 (3.2 mg/kg, 6.3 mg/kg, 12.5 mg/kg, 25 mg/kg, and 50 mg/kg; oral administration; daily; for 15 days; female BALB/c nude mice) treatment in vivo against xenografts of the A431 and SK-OV-3 tumors, and has antitumor activity[1]. Animal Model: Female BALB/c nude mice injected with A431cells[1] Dosage: 3.2 mg/kg, 6.3 mg/kg, 12.5 mg/kg, 25 mg/kg, and 50 mg/kg Administration: Oral administration; daily; for 15 days Result: Antitumor efficacy was obtained at doses between 50 mg/kg and 6.3 mg/kg.

[References]

[1]. Buchdunger E, et al. 4,5-Dianilinophthalimide: a protein-tyrosine kinase inhibitor with selectivity for the epidermal growth factor receptor signal transduction pathway and potent in vivo antitumor activity. Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2334-8.

[2]. Blanchard BJ, et al. Efficient reversal of Alzheimer's disease fibril formation and elimination of neurotoxicity by a small molecule. Proc Natl Acad Sci U S A. 2004 Oct 5;101(40):14326-32.

Chemical & Physical Properties

[ Density]:
1.374 g/cm3

[ Melting Point ]:
199-202℃

[ Molecular Formula ]:
C₂₀H₁₅N₃O₂

[ Molecular Weight ]:
329.35200

[ Exact Mass ]:
329.11600

[ PSA ]:
70.23000

[ LogP ]:
4.53220

[ Storage condition ]:
2-8°C

MSDS

Click to get detail MSDS

Safety Information

[ Personal Protective Equipment ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ Safety Phrases ]:
36/37

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Articles

A chemical-genetic interaction map of small molecules using high-throughput imaging in cancer cells.

Mol. Syst. Biol. 11 , 846, (2015)

Small molecules often affect multiple targets, elicit off-target effects, and induce genotype-specific responses. Chemical genetics, the mapping of the genotype dependence of a small molecule's effect...

Umbelliferone and daphnetin ameliorate carbon tetrachloride-induced hepatotoxicity in rats via nuclear factor erythroid 2-related factor 2-mediated heme oxygenase-1 expression

Environ. Toxicol. Pharmacol. 38(2) , 531-41, (2014)

• This study demonstrates the hepatoprotective effect of umbelliferone and daphnetin. • Both coumarins ameliorate CCl4-induced oxidative stress and hepatotoxicity. • This effect is mediated via the nu...

Gene activation and protein expression following ischaemic stroke: strategies towards neuroprotection.

J. Cell. Mol. Med. 9 , 85-102, (2005)

Current understanding of the patho-physiological events that follow acute ischaemic stroke suggests that treatment regimens could be improved by manipulation of gene transcription and protein activati...