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D4476

SKU: orb1305469

Description

D4476 is a potent, selective, and cell-permeable inhibitor of casein kinase 1 (CK1), exhibiting an IC50 of 300 nM. This small molecule is widely used in biochemical and cellular research to probe CK1 signaling in pathways such as Wnt/β-catenin and circadian rhythms, both in vitro and in vivo.

Research Area

Cardiovascular Research, Cell Biology, Metabolism Research, Signal Transduction, Stem Cell & Developmental Biology

Images & Validation

Key Properties

CAS Number301836-43-1
MW398.41
Purity99.96%
FormulaC23H18N4O3
SMILESNC(=O)c1ccc(cc1)-c1nc(c([nH]1)-c1ccccn1)-c1ccc2OCCOc2c1
TargetApoptosis,ALK,Autophagy,Casein Kinase
SolubilityDMSO:62.5 mg/mL (156.87 mM);Ethanol:19.9 mg/mL (49.95 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (5.02 mM)

Bioactivity

Target IC50
CK1:300 nM
In Vitro
D4476 (10 μM) effectively inhibits CK1 and ALK5 with the activities of about 7% and 22% versus control group, respectively. In H4IIE hepatoma cells, D4476 specifically inhibits the phosphorylation of endogenous forkhead box transcription factor O1a (FOXO1a) on Ser322 and Ser325, without affecting the phosphorylation of other sites. D4476 induces cytotoxicity in ANBL6, INA6 and RPMI8226 lines; MM1S and U266 lines are less sensitive; and OPM1 line is totally resistant. High concentrations (50 μM) D4476 induced toxicity in all multiple myeloma (MM) lines. In MM cells, D4476 increases the protein levels of TP53, P27, and FADD, as well as the cell cycle progression and induction of apoptosis. Treatment of leukemia stem cells (LSCs) with D4476 shows highly selective killing of LSCs over normal HSPCs.
Cell Research
MM cells are seeded in triplicate into 96-well plates in 100 μL culture media. D4476 is added to each well at concentrations of 0, 5, 10, 20, 30, 40, and 50 μM in another 100 μL culture media. Cell viability is measured with MTT at the 72 h drug exposure. Absorbance is measured at 570 nm with spectrophotometer.(Only for Reference)

Storage & Handling

StoragePowder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
Expiration Date12 months from date of receipt.
DisclaimerFor research use only

Alternative Names

ALK5, CaseinKinase, Casein Kinase I Inhibitor, Casein Kinase, Apoptosis, Autophagy, CK1δ, CK1, D4476, D-4476, D 4476, Inhibitor, inhibit

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  • D4476 [orb1225383]

    >98% (HPLC)

    301836-43-1

    398.414

    C23H18N4O3

    500 mg, 25 mg, 2 mg, 5 mg, 50 mg, 1 g, 100 mg, 10 mg
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Key Properties

No computed properties available.

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D4476 (orb1305469)

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% DMSO +
%+
% Tween 80 +
%

Available Sizes

Select a size below

2 mg
$ 90.00
1 ml x 10 mM (in DMSO)
$ 110.00
5 mg
$ 110.00
10 mg
$ 120.00
25 mg
$ 190.00
50 mg
$ 260.00
100 mg
$ 430.00
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