Degraders: The Ultimate Weapon Against Amplified Driver Kinases in Cancer.
Journal
Molecular pharmacology
ISSN: 1521-0111
Titre abrégé: Mol Pharmacol
Pays: United States
ID NLM: 0035623
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
received:
19
04
2021
accepted:
27
01
2022
pubmed:
5
2
2022
medline:
30
4
2022
entrez:
4
2
2022
Statut:
ppublish
Résumé
Amplification of pro-oncogenic kinases is a common genetic alteration driving tumorigenic phenotypes. Cancer cells rely on the amplified kinases to sustain cell proliferation, survival, and growth, presenting an opportunity to develop therapies targeting the amplified kinases. Utilizing small molecule catalytic inhibitors as therapies to target amplified kinases is plagued by de novo resistance driven by increased expression of the target, and amplified kinases can drive tumorigenic phenotypes independent of catalytic activity. Here, we discuss the emergence of proteolysis-targeting chimeras that provide an opportunity to target these oncogenic drivers effectively. SIGNIFICANCE STATEMENT: Protein kinases contribute to tumorigenesis through catalytic and noncatalytic mechanisms, and kinase gene amplifications are well described mechanisms of resistance to small molecule catalytic inhibitors. Repurposing catalytic inhibitors for the development of protein degraders will offer improved clinical benefits by targeting noncatalytic functions of kinases that promote tumorigenesis and overcoming resistance due to amplification.
Identifiants
pubmed: 35115411
pii: molpharm.121.000306
doi: 10.1124/molpharm.121.000306
pmc: PMC9092480
doi:
Substances chimiques
Protein Kinases
EC 2.7.-
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
191-200Informations de copyright
U.S. Government work not protected by U.S. copyright.
Références
Cell. 2020 Dec 10;183(6):1714-1731.e10
pubmed: 33275901
Bioorg Chem. 2022 Feb;119:105508
pubmed: 34959180
J Med Chem. 2019 Aug 22;62(16):7575-7582
pubmed: 31330105
Curr Opin Pharmacol. 2021 Apr;57:175-183
pubmed: 33799000
Nat Rev Drug Discov. 2021 Apr;20(4):247-250
pubmed: 33737725
Nature. 2020 Aug;584(7820):291-297
pubmed: 32728216
J Clin Invest. 2015 May;125(5):1780-9
pubmed: 25932675
Nat Commun. 2020 Sep 18;11(1):4687
pubmed: 32948771
Cancer Res. 1994 Aug 15;54(16):4299-303
pubmed: 8044775
Nat Rev Cancer. 2005 May;5(5):341-54
pubmed: 15864276
Blood. 2020 Apr 30;135(18):1560-1573
pubmed: 32040545
ACS Chem Biol. 2019 Oct 18;14(10):2215-2223
pubmed: 31553577
ACS Chem Biol. 2019 May 17;14(5):882-892
pubmed: 30978004
Nature. 2017 Jan 12;541(7636):169-175
pubmed: 28052061
Nat Commun. 2021 Feb 10;12(1):920
pubmed: 33568647
Cell Rep. 2021 Jan 5;34(1):108532
pubmed: 33406420
Cell Commun Signal. 2011 Oct 28;9(1):23
pubmed: 22035226
Cell Chem Biol. 2020 Sep 17;27(9):1164-1180.e5
pubmed: 32668203
Nat Rev Drug Discov. 2017 Feb;16(2):101-114
pubmed: 27885283
Nat Rev Cancer. 2021 May;21(5):313-324
pubmed: 33731845
Nat Chem Biol. 2021 Jun;17(6):675-683
pubmed: 33753926
Cell Chem Biol. 2018 Jan 18;25(1):67-77.e3
pubmed: 29129716
J Med Chem. 2018 Jan 25;61(2):583-598
pubmed: 28692295
J Med Chem. 2019 Dec 12;62(23):10897-10911
pubmed: 31730343
Curr Opin Chem Biol. 2019 Jun;50:111-119
pubmed: 31004963
Nature. 2000 Aug 17;406(6797):747-52
pubmed: 10963602
Nat Commun. 2019 Jan 10;10(1):131
pubmed: 30631068
ACS Chem Biol. 2019 Sep 20;14(9):2024-2034
pubmed: 31461270
Bioorg Chem. 2018 Dec;81:536-544
pubmed: 30245235
Cancer Discov. 2021 Jun;11(6):1411-1423
pubmed: 33495197
ACS Med Chem Lett. 2018 Mar 18;9(6):540-545
pubmed: 29937979
Drug Discov Today Technol. 2019 Apr;31:15-27
pubmed: 31200855
ACS Chem Biol. 2015 Aug 21;10(8):1831-7
pubmed: 26070106
Mol Cancer Ther. 2019 Jul;18(7):1302-1311
pubmed: 31064868
Bioorg Med Chem Lett. 2019 Jun 1;29(11):1375-1379
pubmed: 30935795
Cell Rep. 2021 Jul 20;36(3):109394
pubmed: 34289372
Eur J Med Chem. 2022 Jan 15;228:114012
pubmed: 34864331
J Med Chem. 2020 Oct 22;63(20):11615-11638
pubmed: 33026811
J Med Chem. 2021 Oct 28;64(20):15477-15502
pubmed: 34652918
Angew Chem Int Ed Engl. 2016 Jan 11;55(2):807-10
pubmed: 26593377
Nature. 2014 Sep 11;513(7517):202-9
pubmed: 25079317
J Med Chem. 2020 Jan 9;63(1):157-162
pubmed: 31804822
Blood. 2021 Dec 9;138(23):2313-2326
pubmed: 34110416
Adv Drug Deliv Rev. 2001 Mar 1;46(1-3):3-26
pubmed: 11259830
Nat Chem Biol. 2020 Nov;16(11):1170-1178
pubmed: 32778845
Front Chem. 2021 Jun 30;9:679120
pubmed: 34277564
J Med Chem. 2018 May 10;61(9):4249-4255
pubmed: 29660984
Nature. 2020 Sep;585(7824):293-297
pubmed: 32494016
Sci Signal. 2010 Nov 23;3(149):ra84
pubmed: 21098728
Cell Chem Biol. 2021 Jul 15;28(7):1032-1047
pubmed: 33930325
Cell Chem Biol. 2018 Jan 18;25(1):88-99.e6
pubmed: 29129717
Eur J Med Chem. 2018 May 10;151:304-314
pubmed: 29627725
J Am Chem Soc. 2018 Dec 12;140(49):17019-17026
pubmed: 30444612
ACS Chem Biol. 2019 Mar 15;14(3):342-347
pubmed: 30807093
Open Biol. 2016 Oct;6(10):
pubmed: 27784791
Nat Chem Biol. 2018 May;14(5):431-441
pubmed: 29581585
Signal Transduct Target Ther. 2019 Dec 24;4:64
pubmed: 31885879
Angew Chem Int Ed Engl. 2019 May 6;58(19):6321-6326
pubmed: 30802347
Clin Cancer Res. 2014 May 1;20(9):2249-56
pubmed: 24789032
Cancer Discov. 2021 Dec 1;11(12):3064-3089
pubmed: 34301793
Commun Biol. 2020 Mar 20;3(1):140
pubmed: 32198438
Nat Chem Biol. 2021 May;17(5):567-575
pubmed: 33664520
Elife. 2020 Aug 17;9:
pubmed: 32804079
Nat Chem Biol. 2015 Aug;11(8):611-7
pubmed: 26075522
Cancers (Basel). 2019 Dec 07;11(12):
pubmed: 31817861
Nat Chem Biol. 2018 Feb;14(2):163-170
pubmed: 29251720
Cell Chem Biol. 2021 Apr 15;28(4):559-566.e15
pubmed: 33513350
Biochem Biophys Res Commun. 2018 Oct 28;505(2):542-547
pubmed: 30274779
ACS Med Chem Lett. 2019 Oct 22;11(10):1855-1862
pubmed: 33062164
Sci Rep. 2018 Sep 10;8(1):13549
pubmed: 30202081
ACS Med Chem Lett. 2017 Sep 14;8(10):1042-1047
pubmed: 29057048
Nat Commun. 2020 Aug 26;11(1):4268
pubmed: 32848159
J Am Chem Soc. 2018 Dec 5;140(48):16428-16432
pubmed: 30427680
Cell Res. 2018 Jul;28(7):779-781
pubmed: 29875397
Nat Chem Biol. 2020 Nov;16(11):1179-1188
pubmed: 32989298
Cancer Res. 2019 Sep 15;79(18):4744-4753
pubmed: 31311809
Cell Chem Biol. 2020 Jan 16;27(1):66-73.e7
pubmed: 31859249
Cell Chem Biol. 2019 Feb 21;26(2):300-306.e9
pubmed: 30595531
ACS Cent Sci. 2016 Dec 28;2(12):927-934
pubmed: 28058282
Eur J Med Chem. 2020 Feb 1;187:111952
pubmed: 31846828
Oncogene. 2000 Dec 11;19(53):6102-14
pubmed: 11156523
J Neurooncol. 1994;22(3):201-7
pubmed: 7760096
Cell Chem Biol. 2020 Aug 20;27(8):998-1014
pubmed: 32795419
Cell. 2020 Apr 2;181(1):102-114
pubmed: 31955850
Chem Biol. 2015 Jun 18;22(6):755-63
pubmed: 26051217
Biochemistry. 2018 Jul 3;57(26):3564-3575
pubmed: 29851337
Clin Exp Metastasis. 2013 Jun;30(5):579-94
pubmed: 23275034
J Am Chem Soc. 2020 Jul 8;142(27):11734-11742
pubmed: 32369353
ACS Chem Biol. 2018 Sep 21;13(9):2758-2770
pubmed: 30137962
J Clin Invest. 2021 Nov 15;131(22):
pubmed: 34554931
J Med Chem. 2019 Mar 14;62(5):2508-2520
pubmed: 30739444
Front Chem. 2021 Apr 20;9:672267
pubmed: 33959589
Int J Mol Sci. 2021 Mar 11;22(6):
pubmed: 33799513
Sci Transl Med. 2010 Dec 15;2(62):62ra93
pubmed: 21160078
Cell Chem Biol. 2018 Jan 18;25(1):78-87.e5
pubmed: 29129718
Eur J Med Chem. 2018 May 10;151:237-247
pubmed: 29625382