Comparative Analysis of BTK Inhibitors and Mechanisms Underlying Adverse Effects.
X-linked agammaglobulinemia
acalabrutinib
atrial fibrillation
diarrhoea
ibrutinib
infection
rash
zanubrutinib
Journal
Frontiers in cell and developmental biology
ISSN: 2296-634X
Titre abrégé: Front Cell Dev Biol
Pays: Switzerland
ID NLM: 101630250
Informations de publication
Date de publication:
2021
2021
Historique:
received:
18
11
2020
accepted:
03
02
2021
entrez:
29
3
2021
pubmed:
30
3
2021
medline:
30
3
2021
Statut:
epublish
Résumé
The cytoplasmic protein-tyrosine kinase BTK plays an essential role for differentiation and survival of B-lineage cells and, hence, represents a suitable drug target. The number of BTK inhibitors (BTKis) in the clinic has increased considerably and currently amounts to at least 22. First-in-class was ibrutinib, an irreversible binder forming a covalent bond to a cysteine in the catalytic region of the kinase, for which we have identified 228 active trials listed at ClinicalTrials.gov. Next-generation inhibitors, acalabrutinib and zanubrutinib, are approved both in the United States and in Europe, and zanubrutinib also in China, while tirabrutinib is currently only registered in Japan. In most cases, these compounds have been used for the treatment of B-lymphocyte tumors. However, an increasing number of trials instead addresses autoimmunity and inflammation in multiple sclerosis, rheumatoid arthritis, pemphigus and systemic lupus erythematosus with the use of either irreversibly binding inhibitors, e.g., evobrutinib and tolebrutinib, or reversibly binding inhibitors, like fenebrutinib. Adverse effects (AEs) have predominantly implicated inhibition of other kinases with a BTKi-binding cysteine in their catalytic domain. Analysis of the reported AEs suggests that ibrutinib-associated atrial fibrillation is caused by binding to ERBB2/HER2 and ERBB4/HER4. However, the binding pattern of BTKis to various additional kinases does not correlate with the common assumption that skin manifestations and diarrhoeas are off-target effects related to EGF receptor inhibition. Moreover, dermatological toxicities, diarrhoea, bleedings and invasive fungal infections often develop early after BTKi treatment initiation and subsequently subside. Conversely, cardiovascular AEs, like hypertension and various forms of heart disease, often persist.
Identifiants
pubmed: 33777941
doi: 10.3389/fcell.2021.630942
pmc: PMC7991787
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
630942Informations de copyright
Copyright © 2021 Estupiñán, Berglöf, Zain and Smith.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Am J Physiol Heart Circ Physiol. 2010 Sep;299(3):H713-22
pubmed: 20543088
EMBO Mol Med. 2015 Jan 30;7(3):240-58
pubmed: 25637383
Blood. 2018 Nov 1;132(18):1985-1988
pubmed: 30021784
Br J Haematol. 2018 Jan;180(1):164-166
pubmed: 27539794
J Immunol. 1990 Sep 15;145(6):1675-80
pubmed: 2391416
Blood. 2001 Nov 15;98(10):3050-7
pubmed: 11698290
Proc Natl Acad Sci U S A. 2015 Feb 17;112(7):2145-50
pubmed: 25646432
N Engl J Med. 2018 Dec 27;379(26):2517-2528
pubmed: 30501481
Blood Rev. 2019 May;35:59-67
pubmed: 30928168
J Pharmacol Exp Ther. 2013 Aug;346(2):219-28
pubmed: 23709115
Cancer Sci. 2020 Sep;111(9):3327-3337
pubmed: 32639651
Cancer Discov. 2018 Oct;8(10):1300-1315
pubmed: 30093506
Leukemia. 2015 Apr;29(4):783-7
pubmed: 25138588
Blood. 2016 Jan 28;127(4):411-9
pubmed: 26542378
Lancet. 2020 Apr 18;395(10232):1278-1291
pubmed: 32305093
Haematologica. 2019 May;104(5):e208-e210
pubmed: 30514799
Blood Adv. 2020 Jun 9;4(11):2439-2450
pubmed: 32492159
Blood. 2019 Aug 15;134(7):641-644
pubmed: 31243043
J Clin Oncol. 2013 Jan 1;31(1):88-94
pubmed: 23045577
Lancet. 2018 Feb 17;391(10121):659-667
pubmed: 29241979
Blood. 2019 Sep 12;134(11):851-859
pubmed: 31340982
J Immunol. 2019 May 15;202(10):2888-2906
pubmed: 30988116
N Engl J Med. 2015 Dec 17;373(25):2425-37
pubmed: 26639149
Cancer Lett. 2019 Oct 1;461:132-143
pubmed: 31310800
Clin Cancer Res. 2020 Aug 15;26(16):4216-4224
pubmed: 32461234
Clin Immunol. 2016 Mar;164:65-77
pubmed: 26821304
Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):13075-80
pubmed: 20615965
J Am Coll Cardiol. 2019 Oct 1;74(13):1667-1678
pubmed: 31558250
Mod Rheumatol. 2019 May;29(3):510-522
pubmed: 29862859
Eur J Haematol. 2018 Apr;100(4):325-334
pubmed: 29285806
PLoS One. 2014 Sep 30;9(9):e107041
pubmed: 25269082
Open Forum Infect Dis. 2017 Feb 09;4(1):ofw261
pubmed: 28480254
Leukemia. 2020 Mar;34(3):787-798
pubmed: 31628428
PLoS One. 2013;8(1):e55128
pubmed: 23383079
Future Microbiol. 2018 May;13:659-669
pubmed: 29790796
Blood. 2019 Nov 28;134(22):1919-1928
pubmed: 31582362
Front Immunol. 2020 Aug 28;11:2158
pubmed: 32983178
Future Cardiol. 2011 Sep;7(5):693-704
pubmed: 21929348
Blood. 2020 Oct 29;136(18):2027-2037
pubmed: 32698195
Medicine (Baltimore). 1996 Nov;75(6):287-99
pubmed: 8982147
PLoS One. 2017 Jul 24;12(7):e0181782
pubmed: 28742141
Arthritis Rheumatol. 2020 Apr 9;:
pubmed: 32270926
Open Heart. 2019 May 8;6(1):e001049
pubmed: 31168393
Blood. 2019 Mar 21;133(12):1298-1307
pubmed: 30642919
ACS Chem Biol. 2016 Oct 21;11(10):2897-2907
pubmed: 27571029
Haematologica. 2020 Oct 13;Online ahead of print:
pubmed: 33054121
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
Haematologica. 2018 May;103(5):874-879
pubmed: 29419429
Blood. 2000 Mar 1;95(5):1663-70
pubmed: 10688822
JACC Clin Electrophysiol. 2018 Dec;4(12):1491-1500
pubmed: 30573111
Lancet Oncol. 2018 Jan;19(1):65-75
pubmed: 29246803
Target Oncol. 2019 Apr;14(2):125-138
pubmed: 30927175
Leukemia. 2019 Oct;33(10):2527-2530
pubmed: 31086260
Oncotarget. 2016 Oct 4;7(40):65968-65981
pubmed: 27602755
N Engl J Med. 2014 Jul 17;371(3):213-23
pubmed: 24881631
J Med Chem. 2019 Sep 12;62(17):7643-7655
pubmed: 31368705
J Infect Dis. 2008 Oct 15;198(8):1243-6
pubmed: 18752432
Cancer Res. 2012 Jul 15;72(14):3512-21
pubmed: 22593188
J Thromb Haemost. 2017 May;15(5):835-847
pubmed: 28182323
Ann Hematol. 2021 Jan;100(1):143-155
pubmed: 32488603
Blood. 2012 Mar 15;119(11):2590-4
pubmed: 22279054
Future Med Chem. 2018 Feb;10(3):343-356
pubmed: 29347836
J Med Chem. 2019 Sep 12;62(17):7923-7940
pubmed: 31381333
Blood. 2018 Sep 6;132(10):1039-1049
pubmed: 30018078
J Clin Oncol. 2017 May 1;35(13):1437-1443
pubmed: 28418267
J Pharmacol Exp Ther. 2017 Nov;363(2):240-252
pubmed: 28882879
J Med Chem. 2019 Apr 11;62(7):3228-3250
pubmed: 30893553
Clin Immunol. 2019 Mar;200:39-42
pubmed: 30690192
Blood. 2015 Mar 26;125(13):2062-7
pubmed: 25573991
Cancers (Basel). 2019 Jun 20;11(6):
pubmed: 31226812
Drugs. 2020 Jun;80(8):835-840
pubmed: 32382949
J Clin Oncol. 2020 Sep 1;38(25):2849-2861
pubmed: 32459600
Lancet Oncol. 2016 Oct;17(10):1409-1418
pubmed: 27637985
J Hematol Oncol. 2020 May 11;13(1):48
pubmed: 32393328
Blood. 2015 Aug 6;126(6):739-45
pubmed: 26059948
Cancer Sci. 2019 May;110(5):1686-1694
pubmed: 30815927
Expert Opin Drug Saf. 2014 May;13(5):535-49
pubmed: 24684184
Am J Clin Dermatol. 2020 Dec;21(6):799-812
pubmed: 32613545
Blood Adv. 2019 May 14;3(9):1553-1562
pubmed: 31088809
Lancet Oncol. 2015 Feb;16(2):169-76
pubmed: 25555420
Haematologica. 2018 Dec;103(12):2097-2108
pubmed: 30026342
J Hematol Oncol. 2016 Mar 09;9:21
pubmed: 26957112
Ann Allergy Asthma Immunol. 2014 Jan;112(1):74-75.e2
pubmed: 24331399
Mol Cancer. 2018 Feb 19;17(1):57
pubmed: 29455639
J Immunol. 2017 Apr 15;198(8):3058-3068
pubmed: 28275136
Cancer. 2017 Jun 15;123(12):2268-2273
pubmed: 28171709
Thromb Haemost. 2019 Aug;119(8):1212-1221
pubmed: 31087308
N Engl J Med. 2016 Jan 28;374(4):323-32
pubmed: 26641137
Br J Haematol. 2019 May;185(4):788-790
pubmed: 30460682
Blood. 2020 Oct 29;136(18):2038-2050
pubmed: 32731259
J Clin Immunol. 2014 Nov;34(8):892-9
pubmed: 25339095
Bioessays. 2001 May;23(5):436-46
pubmed: 11340625
Blood. 2014 Dec 18;124(26):3991-5
pubmed: 25305202
Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8880-5
pubmed: 12072561
Leukemia. 2020 May;34(5):1458-1461
pubmed: 31827243
Blood. 2014 Dec 11;124(25):3829-30
pubmed: 25498454
Blood. 2016 Oct 13;128(15):1940-1943
pubmed: 27503501
J Med Chem. 2020 May 28;63(10):5102-5118
pubmed: 32083858
Eur J Immunol. 2000 Jan;30(1):145-54
pubmed: 10602036
J Clin Oncol. 2018 Sep 20;36(27):2755-2761
pubmed: 30044692
J Clin Oncol. 2021 Feb 20;39(6):565-575
pubmed: 32931398
Pediatrics. 1952 Jun;9(6):722-8
pubmed: 14929630
J Immunol. 1994 Jan 15;152(2):557-65
pubmed: 8283037
Am J Hematol. 2020 Jul;95(7):E174-E178
pubmed: 32267009
Future Oncol. 2020 Apr;16(10):517-523
pubmed: 32207333
J Med Chem. 2018 Mar 22;61(6):2227-2245
pubmed: 29457982
J Thromb Haemost. 2020 Oct;18(10):2672-2684
pubmed: 32511880
Oncogene. 2017 Apr;36(15):2045-2053
pubmed: 27669440
Clin Infect Dis. 2018 Aug 16;67(5):687-692
pubmed: 29509845
J Cell Biol. 2001 Feb 19;152(4):717-28
pubmed: 11266463
Scand J Immunol. 2015 Sep;82(3):208-17
pubmed: 26111359
Lancet Haematol. 2020 Feb;7(2):e112-e121
pubmed: 31866281
Br J Haematol. 2019 Feb;184(4):558-569
pubmed: 30506764
Clin Cancer Res. 2020 Aug 1;26(15):3918-3927
pubmed: 32209572
Haematologica. 2015 Dec;100(12):1571-8
pubmed: 26430171
Int J Mol Sci. 2020 Jul 21;21(14):
pubmed: 32708302
Blood. 2020 Jul 2;136(1):93-105
pubmed: 32202637
Mol Cell Biol. 2006 Jul;26(13):4949-57
pubmed: 16782882
Blood. 2015 Apr 16;125(16):2497-506
pubmed: 25700432
Blood. 2011 Jun 9;117(23):6287-96
pubmed: 21422473
Clin Lymphoma Myeloma Leuk. 2018 Nov;18(11):755-761
pubmed: 30077698
Future Oncol. 2016 Dec;12(23):2741-2753
pubmed: 27522860
Am J Hematol. 2019 Dec;94(12):1353-1363
pubmed: 31512258
Blood Adv. 2019 Dec 23;3(24):4298-4311
pubmed: 31869418
Haematologica. 2017 Oct;102(10):1629-1639
pubmed: 28775119
Eur J Immunol. 1993 Dec;23(12):3109-14
pubmed: 8258324
Ann Oncol. 2018 Jan 1;29(suppl_1):i3-i9
pubmed: 29462253
Curr Drug Targets. 2014;15(13):1200-4
pubmed: 25395105
Blood. 2018 Jan 25;131(4):379-386
pubmed: 29255067
Nature. 1993 Jan 21;361(6409):226-33
pubmed: 8380905
Jpn J Clin Oncol. 2016 Apr;46(4):291-8
pubmed: 26826719
J Am Acad Dermatol. 2013 Sep;69(3):463-72
pubmed: 23602600
Mol Cancer Ther. 2016 Nov;15(11):2586-2597
pubmed: 27573423
Blood. 2013 Oct 10;122(15):2539-49
pubmed: 23886836
J Am Acad Dermatol. 2019 Dec 20;:
pubmed: 31870917
Blood. 2018 Apr 26;131(17):1955-1959
pubmed: 29437588
Biol Blood Marrow Transplant. 2019 Oct;25(10):2002-2007
pubmed: 31260802
Curr Biol. 1998 Oct 8;8(20):1137-40
pubmed: 9778529
Blood. 2017 May 18;129(20):2808-2810
pubmed: 28377400
N Engl J Med. 2014 Jun 12;370(24):2286-94
pubmed: 24869598
Br J Haematol. 2018 Mar;180(5):666-679
pubmed: 29318593
Can J Cardiol. 2018 Mar;34(3):337-341
pubmed: 29475534
Blood. 2020 Apr 9;135(15):1204-1213
pubmed: 31876911
Leukemia. 2017 Jan;31(1):177-185
pubmed: 27282255
Biochim Biophys Acta Gen Subj. 2020 Apr;1864(4):129531
pubmed: 31953125
Blood. 2018 May 24;131(21):2357-2366
pubmed: 29483101