D4476   Click here for help

GtoPdb Ligand ID: 5940

Synonyms: casein kinase I inhibitor | CK1 inhibitor | D 4476
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: A cell-permeant, small molecule inhibitor of protein kinase CK1 [5]. Exhibits in vitro and cellular selectivity for CK1-induced phosphorylation events. D4476 is a useful tool for identifying phosphorylation targets of CK1. Also acts as a transforming growth factor beta receptor 1 inhibitor.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 4
Hydrogen bond donors 2
Rotatable bonds 4
Topological polar surface area 103.12
Molecular weight 398.14
XLogP 3.21
No. Lipinski's rules broken 0
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Canonical SMILES NC(=O)c1ccc(cc1)c1nc(c([nH]1)c1ccccn1)c1ccc2c(c1)OCCO2
Isomeric SMILES NC(=O)c1ccc(cc1)c1nc(c([nH]1)c1ccccn1)c1ccc2c(c1)OCCO2
InChI 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)
1. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011)
Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity.
Nat Biotechnol, 29 (11): 1039-45. [PMID:22037377]
2. Bain J, Plater L, Elliott M, Shpiro N, Hastie CJ, McLauchlan H, Klevernic I, Arthur JS, Alessi DR, Cohen P. (2007)
The selectivity of protein kinase inhibitors: a further update.
Biochem J, 408 (3): 297-315. [PMID:17850214]
3. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013)
A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery.
Biochem J, 451 (2): 313-28. [PMID:23398362]
4. Kurihara T, Sakurai E, Toyomoto M, Kii I, Kawamoto D, Asada T, Tanabe T, Yoshimura M, Hagiwara M, Miyata A. (2014)
Alleviation of behavioral hypersensitivity in mouse models of inflammatory pain with two structurally different casein kinase 1 (CK1) inhibitors.
Mol Pain, 10: 17. [PMID:24612480]
5. Rena G, Bain J, Elliott M, Cohen P. (2004)
D4476, a cell-permeant inhibitor of CK1, suppresses the site-specific phosphorylation and nuclear exclusion of FOXO1a.
EMBO Rep, 5 (1): 60-5. [PMID:14710188]
6. Yang LL, Li GB, Yan HX, Sun QZ, Ma S, Ji P, Wang ZR, Feng S, Zou J, Yang SY. (2012)
Discovery of N6-phenyl-1H-pyrazolo[3,4-d]pyrimidine-3,6-diamine derivatives as novel CK1 inhibitors using common-feature pharmacophore model based virtual screening and hit-to-lead optimization.
Eur J Med Chem, 56: 30-8. [PMID:22944772]