Development of PROTACs to address clinical limitations associated with BTK-targeted kinase inhibitors.
B-cell receptor
BTK
Chronic lymphocytic leukemia
ibrutinib
proteolysis targeting chimera
signaling
Journal
Exploration of targeted anti-tumor therapy
ISSN: 2692-3114
Titre abrégé: Explor Target Antitumor Ther
Pays: United States
ID NLM: 101770662
Informations de publication
Date de publication:
29 Jun 2020
29 Jun 2020
Historique:
entrez:
14
9
2020
pubmed:
15
9
2020
medline:
15
9
2020
Statut:
ppublish
Résumé
Chronic lymphocytic leukemia is a common form of leukemia and is dependent on growth-promoting signaling via the B-cell receptor. The Bruton tyrosine kinase (BTK) is an important mediator of B-cell receptor signaling and the irreversible BTK inhibitor ibrutinib can trigger dramatic clinical responses in treated patients. However, emergence of resistance and toxicity are major limitations which lead to treatment discontinuation. There remains, therefore, a clear need for new therapeutic options. In this review, we discuss recent progress in the development of BTK-targeted proteolysis targeting chimeras (PROTACs) describing how such agents may provide advantages over ibrutinib and highlighting features of PROTACs that are important for the development of effective BTK degrading agents. Overall, PROTACs appear to be an exciting new approach to target BTK. However, development is at a very early stage and considerable progress is required to refine these agents and optimize their drug-like properties before progression to clinical testing.
Identifiants
pubmed: 32924028
doi: 10.37349/etat.2020.00009
pmc: PMC7116064
mid: EMS94608
doi:
Types de publication
Journal Article
Langues
eng
Pagination
131-152Subventions
Organisme : Cancer Research UK
ID : A23669
Pays : United Kingdom
Déclaration de conflit d'intérêts
Conflicts of interest The authors declare that they have no conflicts of interest.
Références
Nat Chem Biol. 2017 May;13(5):514-521
pubmed: 28288108
Expert Opin Drug Discov. 2019 Dec;14(12):1255-1268
pubmed: 31538491
Eur J Immunol. 2006 May;36(5):1285-95
pubmed: 16619289
Proc Natl Acad Sci U S A. 2018 Jul 31;115(31):E7285-E7292
pubmed: 30012605
Blood. 2011 Jan 13;117(2):563-74
pubmed: 20940416
N Engl J Med. 2018 Dec 27;379(26):2517-2528
pubmed: 30501481
J Med Chem. 2018 Feb 8;61(3):918-933
pubmed: 29240418
Comput Struct Biotechnol J. 2019 Jan 25;17:160-176
pubmed: 30788082
Front Immunol. 2019 Feb 06;10:156
pubmed: 30787933
Blood. 2003 Nov 15;102(10):3592-9
pubmed: 12842985
J Cell Mol Med. 2010 Oct;14(10):2337-49
pubmed: 20807283
Medchemcomm. 2019 Aug 12;10(10):1755-1764
pubmed: 31867093
Nat Rev Immunol. 2007 Oct;7(10):778-89
pubmed: 17853903
J Med Chem. 2018 Jan 25;61(2):444-452
pubmed: 29144739
Lancet Oncol. 2016 Feb;17(2):200-211
pubmed: 26655421
J Clin Oncol. 2013 Jan 1;31(1):88-94
pubmed: 23045577
Chem Commun (Camb). 2020 Feb 4;56(10):1521-1524
pubmed: 31922153
Recent Results Cancer Res. 2018;212:87-108
pubmed: 30069626
Leukemia. 2019 Apr;33(4):969-980
pubmed: 30315239
N Engl J Med. 2015 Dec 17;373(25):2425-37
pubmed: 26639149
Nat Rev Drug Discov. 2017 Feb;16(2):101-114
pubmed: 27885283
Blood. 2016 Jun 16;127(24):3015-25
pubmed: 27002119
Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):13075-80
pubmed: 20615965
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
N Engl J Med. 2019 Aug 1;381(5):432-443
pubmed: 31365801
Blood. 2016 Aug 11;128(6):816-26
pubmed: 27301861
Haematologica. 2018 Jun;103(6):931-938
pubmed: 29748447
Nat Rev Dis Primers. 2017 Feb 09;3:17008
pubmed: 28179635
Lancet Oncol. 2019 Jan;20(1):43-56
pubmed: 30522969
J Exp Med. 1999 May 3;189(9):1461-6
pubmed: 10224286
J Biol Chem. 2016 Oct 14;291(42):22136-22148
pubmed: 27542411
Oncogene. 1999 Nov 22;18(49):6853-66
pubmed: 10602461
Curr Opin Chem Biol. 2019 Jun;50:111-119
pubmed: 31004963
J Biol Chem. 2001 Dec 21;276(51):47982-92
pubmed: 11606584
J Med Chem. 2015 Jan 8;58(1):512-6
pubmed: 24712864
Nat Rev Immunol. 2013 Aug;13(8):578-91
pubmed: 23883968
N Engl J Med. 2013 Jul 4;369(1):32-42
pubmed: 23782158
Curr Hematol Malig Rep. 2019 Jun;14(3):197-205
pubmed: 31028669
Blood. 2016 Jun 23;127(25):3192-201
pubmed: 27095788
Haematologica. 2018 May;103(5):874-879
pubmed: 29419429
Blood Lymphat Cancer. 2019 Mar 12;9:9-17
pubmed: 32009829
Best Pract Res Clin Haematol. 2016 Mar;29(1):90-99
pubmed: 27742075
Blood Adv. 2019 Dec 10;3(23):4021-4033
pubmed: 31809536
Pharmacol Ther. 2017 Jun;174:138-144
pubmed: 28223226
Oncotarget. 2015 Jun 20;6(17):15122-36
pubmed: 25944695
Oncogene. 2008 Sep 18;27(42):5635-42
pubmed: 18504428
N Engl J Med. 2014 Jul 17;371(3):213-23
pubmed: 24881631
Haematologica. 2017 Oct;102(10):1796-1805
pubmed: 28751558
Hematology Am Soc Hematol Educ Program. 2017 Dec 8;2017(1):329-337
pubmed: 29222275
J Biol Chem. 1997 Jun 20;272(25):15595-8
pubmed: 9188445
ACS Chem Biol. 2019 Mar 15;14(3):361-368
pubmed: 30721025
J Clin Invest. 2017 Aug 1;127(8):3052-3064
pubmed: 28714866
Immunol Rev. 2019 Sep;291(1):190-213
pubmed: 31402495
Nature. 2015 Oct 22;526(7574):525-30
pubmed: 26466571
Immunol Rev. 2000 Aug;176:19-29
pubmed: 11043765
Nat Immunol. 2011 May;12(5):416-24
pubmed: 21441935
Blood. 2012 Mar 15;119(11):2590-4
pubmed: 22279054
Cell. 1998 Jul 10;94(1):5-8
pubmed: 9674420
Trends Immunol. 2011 Dec;32(12):589-94
pubmed: 22000665
Blood. 2015 Mar 26;125(13):2062-7
pubmed: 25573991
Cell Chem Biol. 2018 Jan 18;25(1):88-99.e6
pubmed: 29129717
Blood. 2018 May 24;131(21):2283-2296
pubmed: 29666114
Leukemia. 2019 Aug;33(8):2105-2110
pubmed: 30858551
ACS Chem Biol. 2019 Mar 15;14(3):342-347
pubmed: 30807093
Blood. 2012 Feb 2;119(5):1182-9
pubmed: 22180443
JAMA Oncol. 2015 Apr;1(1):80-7
pubmed: 26182309
J Biol Chem. 2016 Feb 5;291(6):3043-52
pubmed: 26627823
Mol Cancer Ther. 2016 Dec;15(12):2835-2844
pubmed: 27678331
Immunity. 2007 Jan;26(1):93-104
pubmed: 17239630
Nat Chem Biol. 2015 Aug;11(8):611-7
pubmed: 26075522
J Biol Chem. 2003 Jul 11;278(28):26258-64
pubmed: 12724322
Expert Rev Hematol. 2018 Mar;11(3):185-194
pubmed: 29381098
J Exp Med. 2003 Nov 17;198(10):1539-50
pubmed: 14610042
Blood. 2016 Jan 28;127(4):449-57
pubmed: 26491071
Annu Rev Biochem. 2017 Jun 20;86:193-224
pubmed: 28460188
Blood. 2014 Dec 11;124(25):3829-30
pubmed: 25498454
J Immunol. 2013 Nov 1;191(9):4540-50
pubmed: 24068666
Haematologica. 2016 Jul;101(7):e295-8
pubmed: 27151992
Cell Death Differ. 2018 Jan;25(1):21-26
pubmed: 28984869
Immunity. 2000 Jan;12(1):1-5
pubmed: 10661400
Cell Res. 2018 Jul;28(7):779-781
pubmed: 29875397
Haematologica. 2014 Jul;99(7):1138-48
pubmed: 24986876
Cell Death Differ. 2012 Jan;19(1):67-74
pubmed: 22075983
J Biol Chem. 2001 Oct 19;276(42):38595-601
pubmed: 11507089
Blood. 2014 Nov 13;124(20):3101-9
pubmed: 25170122
Mol Med. 2011;17(11-12):1374-82
pubmed: 21968788
Blood. 2011 Jun 9;117(23):6287-96
pubmed: 21422473
Curr Oncol Rep. 2017 Sep;19(9):61
pubmed: 28755313
Nat Med. 2019 Dec;25(12):1938-1947
pubmed: 31792461
Biochemistry. 2018 Jul 3;57(26):3564-3575
pubmed: 29851337
Nat Struct Mol Biol. 2014 Sep;21(9):803-9
pubmed: 25108355
Biochim Biophys Acta. 2016 Mar;1863(3):401-413
pubmed: 26193078
Proc Natl Acad Sci U S A. 1990 Jun;87(12):4727-31
pubmed: 2191300
Blood. 2013 Oct 10;122(15):2539-49
pubmed: 23886836
Cell Chem Biol. 2018 Jan 18;25(1):78-87.e5
pubmed: 29129718
N Engl J Med. 2014 Jun 12;370(24):2286-94
pubmed: 24869598
Curr Biol. 1998 Oct 8;8(20):1137-40
pubmed: 9778529
Bioorg Med Chem Lett. 2020 Feb 1;30(3):126877
pubmed: 31879210
Lancet Oncol. 2014 Jan;15(1):48-58
pubmed: 24332241
Annu Rev Immunol. 2009;27:199-227
pubmed: 19302039