Utilizing PROTAC technology to address the on-target platelet toxicity associated with inhibition of BCL-X
Journal
Chemical communications (Cambridge, England)
ISSN: 1364-548X
Titre abrégé: Chem Commun (Camb)
Pays: England
ID NLM: 9610838
Informations de publication
Date de publication:
05 Dec 2019
05 Dec 2019
Historique:
pubmed:
23
11
2019
medline:
15
1
2020
entrez:
23
11
2019
Statut:
ppublish
Résumé
BCL-XL, an anti-apoptotic BCL-2 family protein, plays a key role in cancer cell survival. However, the potential of BCL-XL as an anti-cancer target has been hampered by the on-target platelet toxicity because platelets depend on BCL-XL to maintain their viability. Here we report the development of a PROTAC BCL-XL degrader, XZ424, which has increased selectivity for BCL-XL-dependent MOLT-4 cells over human platelets compared with conventional BCL-XL inhibitors. This proof-of-concept study demonstrates the potential of utilizing a PROTAC approach to achieve tissue selectivity.
Identifiants
pubmed: 31754664
doi: 10.1039/c9cc07217a
pmc: PMC7057339
mid: NIHMS1554820
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
CRBN protein, human
0
Isoquinolines
0
bcl-X Protein
0
Thalidomide
4Z8R6ORS6L
pomalidomide
D2UX06XLB5
Ubiquitin-Protein Ligases
EC 2.3.2.27
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
14765-14768Subventions
Organisme : NCI NIH HHS
ID : R01 CA211963
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA219836
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA223371
Pays : United States
Organisme : NIH HHS
ID : S10 OD021758
Pays : United States
Références
J Med Chem. 2018 Jan 25;61(2):462-481
pubmed: 28339196
PLoS One. 2015 Mar 26;10(3):e0120913
pubmed: 25811469
Onco Targets Ther. 2018 Oct 23;11:7301-7314
pubmed: 30425521
J Med Chem. 2019 Jun 13;62(11):5522-5540
pubmed: 31117518
Cell Death Differ. 2015 Jul;22(7):1071-80
pubmed: 25952548
Angew Chem Int Ed Engl. 2016 Jan 11;55(2):807-10
pubmed: 26593377
Drugs. 2016 Jun;76(9):979-87
pubmed: 27260335
J Med Chem. 2019 Sep 12;62(17):8152-8163
pubmed: 31389699
J Med Chem. 2019 Feb 14;62(3):1420-1442
pubmed: 30990042
Cancer Discov. 2017 Feb;7(2):165-176
pubmed: 27979832
Chem Biol. 2015 Jun 18;22(6):755-63
pubmed: 26051217
Science. 2015 Jun 19;348(6241):1376-81
pubmed: 25999370
Nat Rev Mol Cell Biol. 2014 Jan;15(1):49-63
pubmed: 24355989
Nat Rev Cancer. 2002 Apr;2(4):277-88
pubmed: 12001989
J Med Chem. 2018 Jan 25;61(2):444-452
pubmed: 29144739
ACS Med Chem Lett. 2014 Aug 26;5(10):1088-93
pubmed: 25313317
Nat Rev Drug Discov. 2017 Feb;16(2):101-114
pubmed: 27885283
Nat Chem Biol. 2013 Jun;9(6):390-7
pubmed: 23603658
Nat Rev Cancer. 2016 Feb;16(2):99-109
pubmed: 26822577
FEBS J. 2016 Jul;283(14):2661-75
pubmed: 26293580
Chem Commun (Camb). 2019 Jan 2;55(3):369-372
pubmed: 30540295
Oncogene. 2007 Feb 26;26(9):1324-37
pubmed: 17322918
Angew Chem Int Ed Engl. 2017 May 15;56(21):5738-5743
pubmed: 28418626
Chem Commun (Camb). 2017 Jul 4;53(54):7577-7580
pubmed: 28636052
J Med Chem. 2019 Jan 24;62(2):448-466
pubmed: 30525597
Cell Death Differ. 2018 Jan;25(1):65-80
pubmed: 29149100
PLoS One. 2013 Dec 11;8(12):e81809
pubmed: 24349131
Expert Opin Ther Targets. 2013 Jan;17(1):61-75
pubmed: 23173842
Aging (Albany NY). 2017 Mar 8;9(3):955-963
pubmed: 28273655
Nat Med. 2016 Jan;22(1):78-83
pubmed: 26657143
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
Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8554-9
pubmed: 11438690
Blood. 2019 Jan 3;133(1):7-17
pubmed: 30361262
Adv Med. 2014;2014:943648
pubmed: 26556430
Curr Opin Chem Biol. 2017 Aug;39:133-142
pubmed: 28735187
Cell. 2007 Mar 23;128(6):1173-86
pubmed: 17382885
Cell Death Differ. 2007 May;14(5):943-51
pubmed: 17205078
BMC Genomics. 2013 Jan 16;14:1
pubmed: 23323973
J Clin Invest. 2018 Apr 2;128(4):1247-1254
pubmed: 29608140
J Med Chem. 2017 Feb 9;60(3):821-838
pubmed: 27749061
Nat Chem Biol. 2019 Jul;15(7):672-680
pubmed: 31178587
J Med Chem. 2019 Jan 24;62(2):699-726
pubmed: 30540463
J Med Chem. 2019 Jan 24;62(2):941-964
pubmed: 30629437
Sci Transl Med. 2015 Mar 18;7(279):279ra40
pubmed: 25787766
Mol Cancer Ther. 2012 Apr;11(4):1026-35
pubmed: 22302098
J Med Chem. 2018 Jan 25;61(2):482-491
pubmed: 28379698
Nat Commun. 2016 Apr 06;7:11190
pubmed: 27048913
Chem Commun (Camb). 2019 Feb 26;55(18):2704-2707
pubmed: 30758029