D4476

Names

[ Name ]:
D4476

[Synonym ]:
4-(4-(2,3-Dihydrobenzo[1,4]dioxin-6-yl)-5-pyridin-2-yl-1H-imidazol-2-yl)benzamide
4-[4-(2,3-Dihydro-1,4-benzodioxin-6-yl)-5-(pyridin-2-yl)-1H-imidazol-2-yl]benzamide
Benzamide, 4-[4-(2,3-dihydro-1,4-benzodioxin-6-yl)-5-(2-pyridinyl)-1H-imidazol-2-yl]-
CK1 Inhibitor
4-[4-(2,3-Dihydro-1,4-benzodioxin-6-yl)-5-(2-pyridinyl)-1H-imidazol-2-yl]benzamide
Casein Kinase I Inhibitor
D4476

Biological Activity

[Description]:

D4476 is a potent, selective and cell-permeable inhibitor of casein kinase 1(CK1) with an IC50 value of 0.3 μM in vitro.

[Related Catalog]:

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> Cell Cycle/DNA Damage >> Casein Kinase

Signaling Pathways >> Stem Cell/Wnt >> Casein Kinase

Research Areas >> Cancer

[Target]

CK1:0.3 μM (IC50)

[In Vitro]

D4476 is a potent and rather selective inhibitor of CK1 in vitro and in cells. In H4IIE hepatoma cells, D4476 specifically inhibits the phosphorylation of endogenous forkhead box transcription factor O1a (FOXO1a) on Ser322 and Ser325 within its MPD, without affecting the phosphorylation of other sites. CK1δ assayed at 0.1 mM ATP using a phosphorylated peptide TFRPRTSpSNASTIS corresponding to residues 312–325 of FOXO1a is inhibited with an IC50 value of 0.3 μM. The IC50 value for CK1δ decreases progressively as the concentration of ATP is lowered, indicating that D4476 is an ATP-competitive inhibitor of CK1. CK1[1].

[Cell Assay]

D4476 is used for inhibition of Csnk1a1. D4476 is added to leukemia cells cultured in 96-well plates (5,000 cells per well) in medium supplemented with 10 ng/mL mIL-3. A D4476 dose titration is performed by adding 2.5 µM, 5 µM, 10 µM, 20 µM, and 40 µM D4476 to cell cultures in a final DMSO percentage of 0.4%. Similarly, D4476 is added to LSK cells cultured in SFEM medium supplemented with mTpo and mScf. The number of cells after 96 h of treatment is assessed with CountBright absolute counting beads using flow cytometry[2].

[References]

[1]. Rena G, et al. D4476, a cell-permeant inhibitor of CK1, suppresses the site-specific phosphorylation and nuclear exclusion of FOXO1a. EMBO Rep. 2004 Jan;5(1):60-5.

[2]. Järås M, et al. Csnk1a1 inhibition has p53-dependent therapeutic efficacy in acute myeloid leukemia. J Exp Med. 2014 Apr 7;211(4):605-12.

[Related Small Molecules]

Silmitasertib (CX-4945) | TBB | DMAT | Emodin | PF-670462 | SR 3029 | IC 261 | TA-01 | Ellagic acid | TTP 22 | LH846 | Casein Kinase II Inhibitor IV | PF 4800567

Chemical & Physical Properties

[ Density]:
1.3±0.1 g/cm3

[ Boiling Point ]:
675.0±55.0 °C at 760 mmHg

[ Molecular Formula ]:
C₂₃H₁₈N₄O₃

[ Molecular Weight ]:
398.414

[ Flash Point ]:
362.0±31.5 °C

[ Exact Mass ]:
398.137878

[ PSA ]:
103.12000

[ LogP ]:
3.84

[ Vapour Pressure ]:
0.0±2.1 mmHg at 25°C

[ Index of Refraction ]:
1.663

[ 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

[ RIDADR ]:
NONH for all modes of transport

Articles

Acetylation of Beclin 1 inhibits autophagosome maturation and promotes tumour growth.

Nat. Commun. 6 , 7215, (2015)

Beclin 1, a protein essential for autophagy, regulates autophagy by interacting with Vps34 and other cofactors to form the Beclin 1 complex. Modifications of Beclin 1 may lead to the induction, inhibi...

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J. Biol. Chem. 289(23) , 16508-16515, (2014)

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The selectivity of protein kinase inhibitors: a further update.

Biochem. J. 408 , 297-315, (2007)

The specificities of 65 compounds reported to be relatively specific inhibitors of protein kinases have been profiled against a panel of 70-80 protein kinases. On the basis of this information, the ef...

Related Compounds

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