Structure-Based Development of Isoform-Selective Inhibitors of Casein Kinase 1ε vs Casein Kinase 1δ.
Journal
Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531
Informations de publication
Date de publication:
08 06 2023
08 06 2023
Historique:
medline:
9
6
2023
pubmed:
19
5
2023
entrez:
19
5
2023
Statut:
ppublish
Résumé
Specific inhibition of a single kinase isoform is a challenging task due to the highly conserved nature of ATP-binding sites. Casein kinase 1 (CK1) δ and ε share 97% sequence identity in their catalytic domains. From a comparison of the X-ray crystal structures of CK1δ and CK1ε, we developed a potent and highly CK1ε-isoform-selective inhibitor (SR-4133). The X-ray co-crystal structure of the CK1δ-SR-4133 complex reveals that the electrostatic surface between the naphthyl unit of SR-4133 and CK1δ is mismatched, destabilizing the interaction of SR-4133 with CK1δ. Conversely, the hydrophobic surface area resulting from the Asp-Phe-Gly motif (DFG)-out conformation of CK1ε stabilizes the binding of SR-4133 in the ATP-binding pocket of CK1ε, leading to the selective inhibition of CK1ε. The potent CK1ε-selective agents display nanomolar growth inhibition of bladder cancer cells and inhibit the phosphorylation of 4E-BP1 in T24 cells, which is a direct downstream effector of CK1ε.
Identifiants
pubmed: 37204207
doi: 10.1021/acs.jmedchem.2c01180
pmc: PMC10304650
mid: NIHMS1904561
doi:
Substances chimiques
Casein Kinase Idelta
EC 2.7.11.1
Casein Kinases
EC 2.7.11.1
Protein Isoforms
0
Adenosine Triphosphate
8L70Q75FXE
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7162-7178Subventions
Organisme : NCI NIH HHS
ID : R01 CA175094
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA223823
Pays : United States
Organisme : NIGMS NIH HHS
ID : SC2 GM130470
Pays : United States
Références
J Mol Graph. 1996 Feb;14(1):33-8, 27-8
pubmed: 8744570
Bioinformatics. 2010 Jan 15;26(2):198-204
pubmed: 19942586
Molecules. 2017 Mar 24;22(4):
pubmed: 28338621
Front Oncol. 2014 May 19;4:96
pubmed: 24904820
J Chem Theory Comput. 2013 Sep 10;9(9):3878-88
pubmed: 26592383
ACS Med Chem Lett. 2012 Oct 18;3(12):1059-64
pubmed: 24900428
J Chem Theory Comput. 2013 Jul 9;9(7):3084-95
pubmed: 26583988
J Comput Chem. 2018 Sep 30;39(25):2110-2117
pubmed: 30368859
J Am Chem Soc. 2017 Jan 18;139(2):946-957
pubmed: 28009512
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2013 Oct;69(Pt 10):1077-83
pubmed: 24100552
Nat Biotechnol. 2005 Mar;23(3):329-36
pubmed: 15711537
J Comput Chem. 2005 Dec;26(16):1668-88
pubmed: 16200636
Cell. 2018 Sep 20;175(1):171-185.e25
pubmed: 30146162
Int J Biochem Cell Biol. 2011 Apr;43(4):465-9
pubmed: 21145983
J Med Chem. 2018 May 10;61(9):4087-4102
pubmed: 29630366
Chem Biol. 2013 Jun 20;20(6):745-6
pubmed: 23790484
Cancers (Basel). 2022 Mar 05;14(5):
pubmed: 35267653
Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):355-67
pubmed: 21460454
Acta Crystallogr D Biol Crystallogr. 2006 Jan;62(Pt 1):72-82
pubmed: 16369096
Ann Transl Med. 2016 Dec;4(23):474
pubmed: 28090530
Nucleic Acids Res. 2004 Jul 1;32(Web Server issue):W665-7
pubmed: 15215472
Biochem J. 2020 Dec 11;477(23):4603-4621
pubmed: 33306089
Gene. 2019 Oct 5;715:144005
pubmed: 31376410
J Chem Inf Model. 2011 Jun 27;51(6):1199-204
pubmed: 21568278
Cell Signal. 2017 Feb;31:58-65
pubmed: 28057520
Int J Cancer. 2015 Jun 15;136(12):2799-810
pubmed: 25404202
Mol Cell. 2017 Sep 7;67(5):783-798.e20
pubmed: 28886336
Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501
pubmed: 20383002
Nat Rev Cancer. 2009 Jan;9(1):28-39
pubmed: 19104514
Cancer Res. 2014 Jan 1;74(1):201-11
pubmed: 24247720
Sci Rep. 2021 Jan 13;11(1):1116
pubmed: 33441879
Int J Mol Sci. 2020 Nov 27;21(23):
pubmed: 33261128
J Chem Theory Comput. 2021 Feb 9;17(2):1060-1073
pubmed: 33403848
J Med Chem. 2012 Jan 26;55(2):956-60
pubmed: 22168824
Mol Cell. 2022 Jun 2;82(11):2006-2020.e8
pubmed: 35353987
Eur J Med Chem. 2019 Nov 1;181:111581
pubmed: 31400711
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):125-32
pubmed: 20124692
Nat Struct Mol Biol. 2008 Oct;15(10):1109-18
pubmed: 18794843
Eur J Med Chem. 2015;96:308-17
pubmed: 25899335
J Org Chem. 2004 Aug 20;69(17):5578-87
pubmed: 15307726
J Med Chem. 2013 Sep 12;56(17):6819-28
pubmed: 23919824
Amino Acids. 2012 Oct;43(4):1577-91
pubmed: 22331384
Proc Natl Acad Sci U S A. 2005 May 10;102(19):6825-30
pubmed: 15867154
Mol Cancer. 2014 Oct 11;13:231
pubmed: 25306547
Sci Transl Med. 2015 Dec 16;7(318):318ra202
pubmed: 26676609
Front Mol Biosci. 2022 Aug 24;9:916232
pubmed: 36090057
Methods Mol Biol. 2018;1762:199-232
pubmed: 29594774
J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674
pubmed: 19461840
J Phys Chem B. 2014 Feb 20;118(7):1813-24
pubmed: 24479628
Curr Med Chem. 2021;28(8):1585-1604
pubmed: 32660395
Bioorg Med Chem Lett. 2013 Aug 1;23(15):4374-80
pubmed: 23787102
Biophys J. 1997 Mar;72(3):1047-69
pubmed: 9138555
J Biol Chem. 2012 Apr 27;287(18):14672-80
pubmed: 22334660
J Med Chem. 2012 Nov 26;55(22):10307-11
pubmed: 23106386
Nat Commun. 2021 Sep 10;12(1):5386
pubmed: 34508104
Bioorg Med Chem. 2018 Feb 1;26(3):590-602
pubmed: 29289448
Nat Chem Biol. 2020 Oct;16(10):1078-1086
pubmed: 32719556