D-4476
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    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 526754

CAS#: 301836-43-1

Description: D-4476, also known as Casein Kinase I Inhibitor, is a potent, selective and cell-permeant inhibitor of casein kinase 1 (CK1; IC50 = 200 nM from S. pombe,1 300 nM for CK1δ2). D4476 suppresses the site-specific phosphorylation and nuclear exclusion of FOXO1a. 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.


Price and Availability

Size
Price

5mg
USD 225
Size
Price

10mg
USD 350
Size
Price

D 4476, purity > 98%, is in stock. Current shipping out time is about 2 weeks after order is received. CoA, QC data and MSDS documents are available in one week after order is received.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 526754
Name: D-4476
CAS#: 301836-43-1
Chemical Formula: C23H18N4O3
Exact Mass: 398.1379
Molecular Weight: 398.422
Elemental Analysis: C, 69.34; H, 4.55; N, 14.06; O, 12.05


Synonym: D-4476; D 4476; D4476; Casein Kinase I Inhibitor.

IUPAC/Chemical Name: 4-[4-(2,3-dihydro-1,4-benzodioxin-6-yl)-5-(2-pyridinyl)1H-imidazol-2-yl]-benzamide

InChi Key: DPDZHVCKYBCJHW-UHFFFAOYSA-N

InChi Code: InChI=1S/C23H18N4O3/c24-22(28)14-4-6-15(7-5-14)23-26-20(21(27-23)17-3-1-2-10-25-17)16-8-9-18-19(13-16)30-12-11-29-18/h1-10,13H,11-12H2,(H2,24,28)(H,26,27)

SMILES Code: O=C(N)C1=CC=C(C2=NC(C3=CC=C(OCCO4)C4=C3)=C(C5=NC=CC=C5)N2)C=C1


Technical Data

Appearance:
Solid powder

Purity:
>98% (or refer to the Certificate of Analysis)

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:
Soluble in DMSO

Shelf Life:
>2 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code:
293490


References

1: Chia R, Haddock S, Beilina A, Rudenko IN, Mamais A, Kaganovich A, Li Y, Kumaran R, Nalls MA, Cookson MR. Phosphorylation of LRRK2 by casein kinase 1α regulates trans-Golgi clustering via differential interaction with ARHGEF7. Nat Commun. 2014 Dec 15;5:5827. doi: 10.1038/ncomms6827. PubMed PMID: 25500533; PubMed Central PMCID: PMC4268884.

2: Bhattacharya D, Dwivedi VP, Kumar S, Reddy MC, Van Kaer L, Moodley P, Das G. Simultaneous inhibition of T helper 2 and T regulatory cell differentiation by small molecules enhances Bacillus Calmette-Guerin vaccine efficacy against tuberculosis. J Biol Chem. 2014 Nov 28;289(48):33404-11. doi: 10.1074/jbc.M114.600452. Epub 2014 Oct 14. PubMed PMID: 25315774; PubMed Central PMCID: PMC4246096.

3: Rachidi N, Taly JF, Durieu E, Leclercq O, Aulner N, Prina E, Pescher P, Notredame C, Meijer L, Späth GF. Pharmacological assessment defines Leishmania donovani casein kinase 1 as a drug target and reveals important functions in parasite viability and intracellular infection. Antimicrob Agents Chemother. 2014;58(3):1501-15. doi: 10.1128/AAC.02022-13. Epub 2013 Dec 23. PubMed PMID: 24366737; PubMed Central PMCID: PMC3957854.

4: Wang L, Lu A, Zhou HX, Sun R, Zhao J, Zhou CJ, Shen JP, Wu SN, Liang CG. Casein kinase 1 alpha regulates chromosome congression and separation during mouse oocyte meiotic maturation and early embryo development. PLoS One. 2013 May 15;8(5):e63173. doi: 10.1371/journal.pone.0063173. Print 2013. PubMed PMID: 23690993; PubMed Central PMCID: PMC3655170.

5: León-Espinosa G, García E, García-Escudero V, Hernández F, Defelipe J, Avila J. Changes in tau phosphorylation in hibernating rodents. J Neurosci Res. 2013 Jul;91(7):954-62. doi: 10.1002/jnr.23220. Epub 2013 Apr 19. PubMed PMID: 23606524.

6: Stavenuiter F, Gale AJ, Heeb MJ. Phosphorylation of protein S by platelet kinases enhances its activated protein C cofactor activity. FASEB J. 2013 Jul;27(7):2918-25. doi: 10.1096/fj.12-225961. Epub 2013 Apr 11. PubMed PMID: 23580615; PubMed Central PMCID: PMC3688756.

7: Foucher AL, Rachidi N, Gharbi S, Blisnick T, Bastin P, Pemberton IK, Späth GF. Apoptotic marker expression in the absence of cell death in staurosporine-treated Leishmania donovani. Antimicrob Agents Chemother. 2013 Mar;57(3):1252-61. doi: 10.1128/AAC.01983-12. Epub 2012 Dec 21. PubMed PMID: 23263009; PubMed Central PMCID: PMC3591890.

8: Zelenak C, Eberhard M, Jilani K, Qadri SM, Macek B, Lang F. Protein kinase CK1α regulates erythrocyte survival. Cell Physiol Biochem. 2012;29(1-2):171-80. doi: 10.1159/000337598. Epub 2012 Mar 1. PubMed PMID: 22415086.

9: Iguchi Y, Katsuno M, Takagi S, Ishigaki S, Niwa J, Hasegawa M, Tanaka F, Sobue G. Oxidative stress induced by glutathione depletion reproduces pathological modifications of TDP-43 linked to TDP-43 proteinopathies. Neurobiol Dis. 2012 Mar;45(3):862-70. doi: 10.1016/j.nbd.2011.12.002. Epub 2011 Dec 13. PubMed PMID: 22198567.

10: Zyss D, Ebrahimi H, Gergely F. Casein kinase I delta controls centrosome positioning during T cell activation. J Cell Biol. 2011 Nov 28;195(5):781-97. doi: 10.1083/jcb.201106025. PubMed PMID: 22123863; PubMed Central PMCID: PMC3257584.

11: Biswas A, Mukherjee S, Das S, Shields D, Chow CW, Maitra U. Opposing action of casein kinase 1 and calcineurin in nucleo-cytoplasmic shuttling of mammalian translation initiation factor eIF6. J Biol Chem. 2011 Jan 28;286(4):3129-38. doi: 10.1074/jbc.M110.188565. Epub 2010 Nov 17. PubMed PMID: 21084295; PubMed Central PMCID: PMC3024805.

12: Huart AS, MacLaine NJ, Meek DW, Hupp TR. CK1alpha plays a central role in mediating MDM2 control of p53 and E2F-1 protein stability. J Biol Chem. 2009 Nov 20;284(47):32384-94. doi: 10.1074/jbc.M109.052647. Epub 2009 Sep 15. PubMed PMID: 19759023; PubMed Central PMCID: PMC2781653.

13: Rena G, Bain J, Elliott M, Cohen P. 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. PubMed PMID: 14710188; PubMed Central PMCID: PMC1298959.