Small Molecule Inhibitors of Lymphocyte Perforin as Focused Immunosuppressants for Infection and Autoimmunity.
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:
10 11 2022
10 11 2022
Historique:
pubmed:
21
10
2022
medline:
15
11
2022
entrez:
20
10
2022
Statut:
ppublish
Résumé
New drugs that precisely target the immune mechanisms critical for cytotoxic T lymphocyte (CTL) and natural killer (NK) cell driven pathologies are desperately needed. In this perspective, we explore the cytolytic protein perforin as a target for therapeutic intervention. Perforin plays an indispensable role in CTL/NK killing and controls a range of immune pathologies, while being encoded by a single copy gene with no redundancy of function. An immunosuppressant targeting this protein would provide the first-ever therapy focused specifically on one of the principal cell death pathways contributing to allotransplant rejection and underpinning multiple autoimmune and postinfectious diseases. No drugs that selectively block perforin-dependent cell death are currently in clinical use, so this perspective will review published novel small molecule inhibitors, concluding with
Identifiants
pubmed: 36263926
doi: 10.1021/acs.jmedchem.2c01338
pmc: PMC9661472
doi:
Substances chimiques
Perforin
126465-35-8
Immunosuppressive Agents
0
Pore Forming Cytotoxic Proteins
0
Membrane Glycoproteins
0
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
14305-14325Références
J Cell Biol. 2006 Nov 20;175(4):619-30
pubmed: 17116752
Immunity. 2002 Mar;16(3):417-28
pubmed: 11911826
J Cell Biol. 2003 Jan 20;160(2):223-33
pubmed: 12538642
Mol Pharm. 2020 Jun 1;17(6):1987-1995
pubmed: 32343897
J Immunol. 1994 Nov 1;153(9):3938-47
pubmed: 7930604
Blood. 2005 Sep 15;106(6):2215-20
pubmed: 15928035
Faraday Discuss. 2021 Dec 24;232(0):236-255
pubmed: 34545865
J Med Chem. 2010 Apr 8;53(7):2719-40
pubmed: 20131845
Pharmacol Rev. 2011 Sep;63(3):750-71
pubmed: 21737530
J Innate Immun. 2011;3(4):395-402
pubmed: 21411978
Front Immunol. 2021 Feb 22;12:597951
pubmed: 33692780
Blood. 2010 Feb 25;115(8):1582-93
pubmed: 20038786
Immunol Lett. 1997 Mar;55(3):139-44
pubmed: 9161879
Proc Natl Acad Sci U S A. 1999 Oct 12;96(21):12079-84
pubmed: 10518579
Bioorg Med Chem. 2012 Feb 1;20(3):1319-36
pubmed: 22244072
Am J Pathol. 1998 Aug;153(2):417-28
pubmed: 9708802
J Exp Med. 1997 Oct 6;186(7):989-97
pubmed: 9314549
J Vet Med Sci. 2012 Jul;74(7):917-22
pubmed: 22322188
Cell Death Differ. 2013 Sep;20(9):1183-93
pubmed: 23744295
Immunology. 1997 Jul;91(3):493-500
pubmed: 9301542
Autoimmunity. 1998;27(2):109-22
pubmed: 9583742
Nat Rev Immunol. 2002 Jun;2(6):401-9
pubmed: 12093006
Nat Immunol. 2013 May;14(5):500-8
pubmed: 23525088
Sci Rep. 2019 Sep 6;9(1):12860
pubmed: 31492955
Bioorg Med Chem Lett. 2016 Jan 15;26(2):355-360
pubmed: 26711151
Blood. 2013 Apr 4;121(14):2659-68
pubmed: 23377437
Ann N Y Acad Sci. 2000;922:27-35
pubmed: 11193902
EMBO Rep. 2017 Oct;18(10):1775-1785
pubmed: 28808112
J Exp Med. 2000 Nov 20;192(10):1403-14
pubmed: 11085743
Immunity. 2009 May;30(5):684-95
pubmed: 19446473
Sci Adv. 2022 Feb 11;8(6):eabk3147
pubmed: 35148176
Annu Rev Cell Dev Biol. 2007;23:495-517
pubmed: 17506701
Br J Haematol. 2009 Oct;147(2):192-9
pubmed: 19796268
Blood. 2020 Feb 20;135(8):582-584
pubmed: 31932842
Nat Nanotechnol. 2017 May;12(5):467-473
pubmed: 28166206
Annu Rev Immunol. 2001;19:375-96
pubmed: 11244041
Nat Rev Immunol. 2015 Jun;15(6):388-400
pubmed: 25998963
Immunol Rev. 2013 Nov;256(1):107-17
pubmed: 24117816
Cell. 1991 Mar 22;64(6):1175-81
pubmed: 2004423
J Biol Chem. 2005 Mar 4;280(9):8426-34
pubmed: 15576364
Bioorg Med Chem. 2011 Jul 1;19(13):4091-100
pubmed: 21664824
Clin Liver Dis. 2021 Nov;25(4):711-724
pubmed: 34593149
J Pharm Pharmacol. 2001 Apr;53(4):497-503
pubmed: 11341366
Mol Pharm. 2016 Jul 5;13(7):2484-91
pubmed: 27266990
Nat Immunol. 2011 Jun 19;12(8):770-7
pubmed: 21685908
J Immunol. 1996 May 15;156(10):3678-86
pubmed: 8621902
Nat Rev Drug Discov. 2018 Aug;17(8):559-587
pubmed: 29700501
Curr Opin Immunol. 2003 Oct;15(5):560-5
pubmed: 14499265
Trends Biochem Sci. 2017 Apr;42(4):245-254
pubmed: 27932073
J Exp Med. 1997 Mar 3;185(5):855-66
pubmed: 9120391
Nat Commun. 2019 Nov 27;10(1):5396
pubmed: 31776337
PLoS Pathog. 2013;9(7):e1003504
pubmed: 23874205
Am J Transplant. 2007 Aug;7(8):1884-96
pubmed: 17617852
Chem Biol Interact. 2021 Aug 25;345:109560
pubmed: 34153225
Biochemistry. 1993 Apr 20;32(15):3902-6
pubmed: 8385991
J Immunol. 2020 May 15;204(10):2818-2828
pubmed: 32269094
Expert Opin Drug Deliv. 2011 Apr;8(4):415-33
pubmed: 21348773
Res Commun Mol Pathol Pharmacol. 2001;110(3-4):229-37
pubmed: 12760490
Biochem Pharmacol. 2011 Jan 15;81(2):251-8
pubmed: 20934407
FEBS Lett. 1995 Feb 6;359(1):53-9
pubmed: 7851530
Nature. 2010 Nov 18;468(7322):447-51
pubmed: 21037563
Nat Rev Immunol. 2002 Oct;2(10):735-47
pubmed: 12360212
Expert Opin Drug Discov. 2012 Jul;7(7):549-60
pubmed: 22607309
Immunol Rev. 2010 May;235(1):93-104
pubmed: 20536557
J Org Chem. 2009 Jan 16;74(2):710-8
pubmed: 19072237
Infect Immun. 2017 Apr 21;85(5):
pubmed: 28264905
J Med Chem. 2013 Dec 12;56(23):9542-55
pubmed: 24195776
Neurol Res. 2018 Jan;40(1):62-67
pubmed: 29105578
Mol Neurobiol. 2020 Nov;57(11):4563-4577
pubmed: 32754897
Curr Drug Metab. 2019;20(2):91-102
pubmed: 30129408
ACS Med Chem Lett. 2010 Jan 19;1(1):39-43
pubmed: 24900173
Nephrology (Carlton). 2018 Jul;23 Suppl 2:45-51
pubmed: 29968416
Front Immunol. 2021 Jul 07;12:665718
pubmed: 34305896
Mol Cell Biol. 1999 Dec;19(12):8604-15
pubmed: 10567584
J Exp Med. 2004 Sep 20;200(6):811-6
pubmed: 15365097
J Chem Inf Model. 2013 Jan 28;53(1):39-55
pubmed: 23198812
Blood. 2005 Jun 15;105(12):4700-6
pubmed: 15755897
Nat Commun. 2019 Dec 18;10(1):5779
pubmed: 31852955
FASEB J. 2000 Jul;14(10):1265-78
pubmed: 10877819
J Cell Biol. 1990 Dec;111(6 Pt 1):2327-40
pubmed: 2277062
Brain. 2020 Dec 1;143(12):3717-3733
pubmed: 33118032
J Exp Med. 1998 Feb 16;187(4):451-60
pubmed: 9463395
FEBS J. 2016 Mar;283(5):947-61
pubmed: 26756195
Front Immunol. 2013 Dec 12;4:441
pubmed: 24376445
Bioorg Med Chem Lett. 2017 Feb 15;27(4):1050-1054
pubmed: 28110869
Eur J Med Chem. 2017 Sep 8;137:139-155
pubmed: 28582670
J Pathol. 1993 May;170(1):53-8
pubmed: 8392106
Cell Mol Immunol. 2022 Jul;19(7):777-790
pubmed: 35468944
J Med Chem. 2020 Mar 12;63(5):2229-2239
pubmed: 31525966
ACS Pharmacol Transl Sci. 2022 May 31;5(6):429-439
pubmed: 35711815
Cell Death Differ. 2010 Apr;17(4):577-85
pubmed: 19927156
J Biol Chem. 2004 May 21;279(21):22236-42
pubmed: 15028722
Radiat Res. 2010 Oct;174(4):480-9
pubmed: 20726712
Science. 2007 Sep 14;317(5844):1548-51
pubmed: 17717151
Nat Commun. 2018 Nov 15;9(1):4805
pubmed: 30442932
Nat Commun. 2015 May 22;6:7250
pubmed: 25998567
Brain Res. 2000 Oct 6;879(1-2):115-21
pubmed: 11011012
Int J Pharm. 2019 Nov 25;571:118714
pubmed: 31610281
Otolaryngol Clin North Am. 2010 Aug;43(4):753-68
pubmed: 20599080
Annu Rev Biochem. 1986;55:663-700
pubmed: 2874766
Cell Metab. 2021 Jul 6;33(7):1358-1371.e5
pubmed: 33989521
Eur J Pharm Sci. 2017 Nov 15;109:146-161
pubmed: 28782609
Int J Pharm. 2016 Feb 10;498(1-2):205-16
pubmed: 26705152
J Exp Med. 2015 Mar 9;212(3):307-17
pubmed: 25732304
Biochemistry. 1990 Dec 25;29(51):11229-35
pubmed: 2125503
J Exp Biol. 1997 Jan;200(Pt 1):1-8
pubmed: 9023991
Biosci Biotechnol Biochem. 1996 Oct;60(10):1726-8
pubmed: 8987676
Cold Spring Harb Perspect Med. 2018 Apr 2;8(4):
pubmed: 29358315
Nat Rev Immunol. 2006 Dec;6(12):940-52
pubmed: 17124515
J Med Chem. 2008 Dec 11;51(23):7614-24
pubmed: 19007200