Phenyl‐Glutarimides: Alternative Cereblon Binders for the Design of PROTACs

Targeting cereblon (CRBN) is currently one of the most frequently reported proteolysis‐targeting chimera (PROTAC) approaches, owing to favorable drug‐like properties of CRBN ligands, immunomodulatory imide drugs (IMiDs). However, IMiDs are known to be inherently unstable, readily undergoing hydrolys...

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Vydáno v:Angewandte Chemie International Edition Ročník 60; číslo 51; s. 26663 - 26670
Hlavní autoři: Min, Jaeki, Mayasundari, Anand, Keramatnia, Fatemeh, Jonchere, Barbara, Yang, Seung Wook, Jarusiewicz, Jamie, Actis, Marisa, Das, Sourav, Young, Brandon, Slavish, Jake, Yang, Lei, Li, Yong, Fu, Xiang, Garrett, Shalandus H., Yun, Mi‐Kyung, Li, Zhenmei, Nithianantham, Stanley, Chai, Sergio, Chen, Taosheng, Shelat, Anang, Lee, Richard E., Nishiguchi, Gisele, White, Stephen W., Roussel, Martine F., Potts, Patrick Ryan, Fischer, Marcus, Rankovic, Zoran
Médium: Journal Article
Jazyk:angličtina
Vydáno: WEINHEIM Wiley 13.12.2021
Wiley Subscription Services, Inc
Wiley-VCH Verlag
Vydání:International ed. in English
Témata:
Acute myeloid leukemia
Adaptor Proteins, Signal Transducing - chemistry
Binders
Body fluids
cereblon
Chemistry
Chemistry, Multidisciplinary
Human health and pathology
Humans
Hydrolysis
IMiD
Immunomodulation
Leukemia
Life Sciences
Ligands
Myeloid leukemia
phenyl glutarimide
Physical Sciences
Piperidones - chemistry
PROTAC
Proteolysis
Science & Technology
Ubiquitin-Protein Ligases - chemistry
CC-90009
phenyl glutarimide
COMPLEX
PROTAC
UBIQUITIN LIGASE
HYDROLYSIS
THALIDOMIDE
GSPT1
cereblon
METABOLISM
DEGRADER
PG
E3 LIGASE MODULATOR
TARGETED PROTEIN-DEGRADATION
IMiD
Ubiquitin-Protein Ligases
Hydrolysis
Signal Transducing
Proteolysis
Humans
Piperidones
Adaptor Proteins
ISSN:1433-7851, 1521-3773, 1521-3773
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Abstract Targeting cereblon (CRBN) is currently one of the most frequently reported proteolysis‐targeting chimera (PROTAC) approaches, owing to favorable drug‐like properties of CRBN ligands, immunomodulatory imide drugs (IMiDs). However, IMiDs are known to be inherently unstable, readily undergoing hydrolysis in body fluids. Here we show that IMiDs and IMiD‐based PROTACs rapidly hydrolyze in commonly utilized cell media, which significantly affects their cell efficacy. We designed novel CRBN binders, phenyl glutarimide (PG) analogues, and showed that they retained affinity for CRBN with high ligand efficiency (LE >0.48) and displayed improved chemical stability. Our efforts led to the discovery of PG PROTAC 4 c (SJ995973), a uniquely potent degrader of bromodomain and extra‐terminal (BET) proteins that inhibited the viability of human acute myeloid leukemia MV4‐11 cells at low picomolar concentrations (IC50=3 pM; BRD4 DC50=0.87 nM). These findings strongly support the utility of PG derivatives in the design of CRBN‐directed PROTACs. IMiD‐based PROTACs rapidly hydrolyze in commonly utilized cell media, which significantly affects their cell efficacy. We designed novel BET PROTACs based on phenyl glutarimide (PG) and showed that they retained affinity for CRBN and displayed improved chemical stability. To demonstrate the utility of PG‐based PROTACs we developed SJ995973 (4 c), a uniquely potent degrader of BET proteins.
AbstractList Targeting cereblon (CRBN) is currently one of the most frequently reported proteolysis‐targeting chimera (PROTAC) approaches, owing to favorable drug‐like properties of CRBN ligands, immunomodulatory imide drugs (IMiDs). However, IMiDs are known to be inherently unstable, readily undergoing hydrolysis in body fluids. Here we show that IMiDs and IMiD‐based PROTACs rapidly hydrolyze in commonly utilized cell media, which significantly affects their cell efficacy. We designed novel CRBN binders, phenyl glutarimide (PG) analogues, and showed that they retained affinity for CRBN with high ligand efficiency (LE >0.48) and displayed improved chemical stability. Our efforts led to the discovery of PG PROTAC 4 c (SJ995973), a uniquely potent degrader of bromodomain and extra‐terminal (BET) proteins that inhibited the viability of human acute myeloid leukemia MV4‐11 cells at low picomolar concentrations (IC 50 =3 pM; BRD4 DC 50 =0.87 nM). These findings strongly support the utility of PG derivatives in the design of CRBN‐directed PROTACs.
Targeting cereblon (CRBN) is currently one of the most frequently reported proteolysis‐targeting chimera (PROTAC) approaches, owing to favorable drug‐like properties of CRBN ligands, immunomodulatory imide drugs (IMiDs). However, IMiDs are known to be inherently unstable, readily undergoing hydrolysis in body fluids. Here we show that IMiDs and IMiD‐based PROTACs rapidly hydrolyze in commonly utilized cell media, which significantly affects their cell efficacy. We designed novel CRBN binders, phenyl glutarimide (PG) analogues, and showed that they retained affinity for CRBN with high ligand efficiency (LE >0.48) and displayed improved chemical stability. Our efforts led to the discovery of PG PROTAC 4 c (SJ995973), a uniquely potent degrader of bromodomain and extra‐terminal (BET) proteins that inhibited the viability of human acute myeloid leukemia MV4‐11 cells at low picomolar concentrations (IC50=3 pM; BRD4 DC50=0.87 nM). These findings strongly support the utility of PG derivatives in the design of CRBN‐directed PROTACs.
Targeting cereblon (CRBN) is currently one of the most frequently reported proteolysis-targeting chimera (PROTAC) approaches, owing to favorable drug-like properties of CRBN ligands, immunomodulatory imide drugs (IMiDs). However, IMiDs are known to be inherently unstable, readily undergoing hydrolysis in body fluids. Here we show that IMiDs and IMiD-based PROTACs rapidly hydrolyze in commonly utilized cell media, which significantly affects their cell efficacy. We designed novel CRBN binders, phenyl glutarimide (PG) analogues, and showed that they retained affinity for CRBN with high ligand efficiency (LE >0.48) and displayed improved chemical stability. Our efforts led to the discovery of PG PROTAC 4c (SJ995973), a uniquely potent degrader of bromodomain and extra-terminal (BET) proteins that inhibited the viability of human acute myeloid leukemia MV4–11 cells at low picomolar concentrations (IC50 = 3 pM; BRD4 DC50 = 0.87 nM). These findings strongly support the utility of PG derivatives in the design of CRBN-directed PROTACs. IMiD-based PROTACs rapidly hydrolyze in commonly utilized cell media, which significantly affects their cell efficacy. We designed novel BET PROTACs based on phenyl glutarimide (PG) and showed that they retained affinity for CRBN and displayed improved chemical stability. To demonstrate the utility of PG-based PROTACs we developed SJ995973 (4c), a uniquely potent degrader of BET proteins.
Targeting cereblon (CRBN) is currently one of the most frequently reported proteolysis-targeting chimera (PROTAC) approaches, owing to favorable drug-like properties of CRBN ligands, immunomodulatory imide drugs (IMiDs). However, IMiDs are known to be inherently unstable, readily undergoing hydrolysis in body fluids. Here we show that IMiDs and IMiD-based PROTACs rapidly hydrolyze in commonly utilized cell media, which significantly affects their cell efficacy. We designed novel CRBN binders, phenyl glutarimide (PG) analogues, and showed that they retained affinity for CRBN with high ligand efficiency (LE >0.48) and displayed improved chemical stability. Our efforts led to the discovery of PG PROTAC 4 c (SJ995973), a uniquely potent degrader of bromodomain and extra-terminal (BET) proteins that inhibited the viability of human acute myeloid leukemia MV4-11 cells at low picomolar concentrations (IC50 =3 pM; BRD4 DC50 =0.87 nM). These findings strongly support the utility of PG derivatives in the design of CRBN-directed PROTACs.Targeting cereblon (CRBN) is currently one of the most frequently reported proteolysis-targeting chimera (PROTAC) approaches, owing to favorable drug-like properties of CRBN ligands, immunomodulatory imide drugs (IMiDs). However, IMiDs are known to be inherently unstable, readily undergoing hydrolysis in body fluids. Here we show that IMiDs and IMiD-based PROTACs rapidly hydrolyze in commonly utilized cell media, which significantly affects their cell efficacy. We designed novel CRBN binders, phenyl glutarimide (PG) analogues, and showed that they retained affinity for CRBN with high ligand efficiency (LE >0.48) and displayed improved chemical stability. Our efforts led to the discovery of PG PROTAC 4 c (SJ995973), a uniquely potent degrader of bromodomain and extra-terminal (BET) proteins that inhibited the viability of human acute myeloid leukemia MV4-11 cells at low picomolar concentrations (IC50 =3 pM; BRD4 DC50 =0.87 nM). These findings strongly support the utility of PG derivatives in the design of CRBN-directed PROTACs.
Targeting cereblon (CRBN) is currently one of the most frequently reported proteolysis-targeting chimera (PROTAC) approaches, owing to favorable drug-like properties of CRBN ligands, immunomodulatory imide drugs (IMiDs). However, IMiDs are known to be inherently unstable, readily undergoing hydrolysis in body fluids. Here we show that IMiDs and IMiD-based PROTACs rapidly hydrolyze in commonly utilized cell media, which significantly affects their cell efficacy. We designed novel CRBN binders, phenyl glutarimide (PG) analogues, and showed that they retained affinity for CRBN with high ligand efficiency (LE >0.48) and displayed improved chemical stability. Our efforts led to the discovery of PG PROTAC 4 c (SJ995973), a uniquely potent degrader of bromodomain and extra-terminal (BET) proteins that inhibited the viability of human acute myeloid leukemia MV4-11 cells at low picomolar concentrations (IC =3 pM; BRD4 DC =0.87 nM). These findings strongly support the utility of PG derivatives in the design of CRBN-directed PROTACs.
Targeting cereblon (CRBN) is currently one of the most frequently reported proteolysis‐targeting chimera (PROTAC) approaches, owing to favorable drug‐like properties of CRBN ligands, immunomodulatory imide drugs (IMiDs). However, IMiDs are known to be inherently unstable, readily undergoing hydrolysis in body fluids. Here we show that IMiDs and IMiD‐based PROTACs rapidly hydrolyze in commonly utilized cell media, which significantly affects their cell efficacy. We designed novel CRBN binders, phenyl glutarimide (PG) analogues, and showed that they retained affinity for CRBN with high ligand efficiency (LE >0.48) and displayed improved chemical stability. Our efforts led to the discovery of PG PROTAC 4 c (SJ995973), a uniquely potent degrader of bromodomain and extra‐terminal (BET) proteins that inhibited the viability of human acute myeloid leukemia MV4‐11 cells at low picomolar concentrations (IC50=3 pM; BRD4 DC50=0.87 nM). These findings strongly support the utility of PG derivatives in the design of CRBN‐directed PROTACs. IMiD‐based PROTACs rapidly hydrolyze in commonly utilized cell media, which significantly affects their cell efficacy. We designed novel BET PROTACs based on phenyl glutarimide (PG) and showed that they retained affinity for CRBN and displayed improved chemical stability. To demonstrate the utility of PG‐based PROTACs we developed SJ995973 (4 c), a uniquely potent degrader of BET proteins.
Author Chai, Sergio
Keramatnia, Fatemeh
Li, Yong
Potts, Patrick Ryan
Shelat, Anang
Nithianantham, Stanley
Li, Zhenmei
Chen, Taosheng
Rankovic, Zoran
Young, Brandon
Yang, Seung Wook
Slavish, Jake
Yun, Mi‐Kyung
Jonchere, Barbara
White, Stephen W.
Garrett, Shalandus H.
Roussel, Martine F.
Actis, Marisa
Mayasundari, Anand
Fu, Xiang
Min, Jaeki
Lee, Richard E.
Yang, Lei
Fischer, Marcus
Das, Sourav
Jarusiewicz, Jamie
Nishiguchi, Gisele
AuthorAffiliation d Department of Structural Biology, St. Jude Children’s Research Hospital, Memphis, Tennessee 38105, United States
c Department of Cell & Molecular Biology, St. Jude Children’s Research Hospital, Memphis, Tennessee 38105, United States
a Department of Chemical Biology and Therapeutics, St. Jude Children’s Research Hospital, Memphis, Tennessee 38105, United States
b Department of Tumor Cell Biology, St. Jude Children’s Research Hospital, Memphis, Tennessee 38105, United States
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/34614283$$D View this record in MEDLINE/PubMed
https://u-picardie.hal.science/hal-03720142$$DView record in HAL
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Cites_doi 10.1021/acs.jmedchem.0c01313
10.18632/oncotarget.1659
10.1182/blood-2019-123966
10.1016/j.chembiol.2015.05.009
10.1016/j.ejmech.2019.01.023
10.1038/s41573-019-0047-y
10.1002/cmdc.201800271
10.1182/blood-2015-02-628669
10.1021/acs.bioconjchem.0c00507
10.1016/j.ddtec.2019.02.004
10.1016/j.bmcl.2019.04.030
10.1021/jacs.8b10320
10.1016/j.ddtec.2019.04.001
10.1021/acs.jmedchem.8b00506
10.1021/acs.jmedchem.7b01406
10.1016/j.tips.2020.02.006
10.1111/j.1476-5381.1965.tb02054.x
10.1038/nchembio.2329
10.1182/blood-2019-127892
10.1111/j.1476-5381.1965.tb02053.x
10.1182/blood.2020006846
10.1038/s41589-019-0362-y
10.1016/j.cbpa.2019.02.022
10.1126/science.aab1433
10.1126/science.1177319
10.1073/pnas.141230798
10.1016/S1359-6446(04)03069-7
10.1016/j.bbrc.2019.11.007
10.1126/science.aat0572
10.1007/s11060-012-0978-1
10.1038/nature18611
10.1038/nature13527
10.1021/tx9801817
10.1038/NCHEMBIO.2329
ContentType Journal Article
Copyright 2021 Wiley‐VCH GmbH
2021 Wiley-VCH GmbH.
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Issue 51
Keywords CC-90009
phenyl glutarimide
COMPLEX
PROTAC
UBIQUITIN LIGASE
HYDROLYSIS
THALIDOMIDE
GSPT1
cereblon
METABOLISM
DEGRADER
PG
E3 LIGASE MODULATOR
TARGETED PROTEIN-DEGRADATION
IMiD
Ubiquitin-Protein Ligases
Hydrolysis
Signal Transducing
Proteolysis
Humans
Piperidones
Adaptor Proteins
Language English
License 2021 Wiley-VCH GmbH.
Distributed under a Creative Commons Attribution 4.0 International License: http://creativecommons.org/licenses/by/4.0
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Notes These authors contributed equally to this work.
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Matyskiela, ME (WOS:000379912600050) 2016; 535
SCHUMACHER, H (WOS:A19656906900005) 1965; 25
Lopez-Girona, A (WOS:000577160406084) 2019; 134
Mu, XP (WOS:000507487200003) 2020; 521
Winter, GE (WOS:000356449500055) 2015; 348
Venkataraman, S (WOS:000336966600003) 2014; 5
Ito, T (WOS:000275418700032) 2010; 327
Milde, T (WOS:000311208300004) 2012; 110
Edmondson, SD (WOS:000468145300002) 2019; 29
Gadd, MS (WOS:000399004000012) 2017; 13
Nishiguchi, G (WOS:000662187100013) 2021; 64
Qin, C (WOS:000441484300015) 2018; 61
Burslem, GM (WOS:000441432700002) 2018; 13
Paiva, SL (WOS:000473839100014) 2019; 50
Lin, WW (WOS:000592907700013) 2020; 31
Chessum, NEA (WOS:000425063400020) 2018; 61
Yang, Chao-Yie (MEDLINE:31200858) 2019; 31
SCHUMACHER, H (WOS:A19656906900006) 1965; 25
Kim, SA (WOS:000461402400006) 2019; 166
Reist, M (WOS:000077737800019) 1998; 11
(000718932200001.25) 2019
Sakamoto, KM (WOS:000169967000064) 2001; 98
Hopkins, AL (WOS:000221394000005) 2004; 9
Sievers, QL (WOS:000450460000038) 2018; 362
Lu, J (WOS:000358411900009) 2015; 22
Schapira, M (WOS:000499643000015) 2019; 18
Chang, YC (WOS:000744210800007) 2021; 138
Burslem, GM (WOS:000452693800010) 2018; 140
Chamberlain, Philip P (MEDLINE:31200856) 2019; 31
Fischer, ES (WOS:000339908000028) 2014; 512
Hagner, PR (WOS:000360519600013) 2015; 126
Chamberlain, PP (WOS:000487965400007) 2019; 15
Kostic, M (WOS:000527560400005) 2020; 41
Yap (000718932200001.23) 2021
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Uy, GL (WOS:000518218500460) 2019; 134
References_xml – volume: 31
  start-page: 2564
  year: 2020
  end-page: 2575
  publication-title: Bioconjugate Chem.
– volume: 64
  start-page: 7296
  year: 2021
  end-page: 7311
  publication-title: J. Med. Chem.
– volume: 31
  start-page: 43
  year: 2019
  end-page: 51
  publication-title: Drug Discovery Today Technol.
– volume: 22
  start-page: 755
  year: 2015
  end-page: 763
  publication-title: Chem. Biol.
– volume: 61
  start-page: 918
  year: 2018
  end-page: 933
  publication-title: J. Med. Chem.
– volume: 15
  start-page: 937
  year: 2019
  end-page: 944
  publication-title: Nat. Chem. Biol.
– year: 2021
– volume: 126
  start-page: 779
  year: 2015
  end-page: 789
  publication-title: Blood
– volume: 362
  year: 2018
  publication-title: Science
– volume: 25
  start-page: 338
  year: 1965
  end-page: 351
  publication-title: Br. J. Pharmacol. Chemother.
– volume: 98
  start-page: 8554
  year: 2001
  end-page: 8559
  publication-title: Proc. Natl. Acad. Sci. USA
– volume: 13
  start-page: 514
  year: 2017
  end-page: 521
  publication-title: Nat. Chem. Biol.
– volume: 512
  start-page: 49
  year: 2014
  end-page: 53
  publication-title: Nature
– volume: 348
  start-page: 1376
  year: 2015
  end-page: 1381
  publication-title: Science
– volume: 327
  start-page: 1345
  year: 2010
  end-page: 1350
  publication-title: Science
– volume: 41
  start-page: 305
  year: 2020
  end-page: 317
  publication-title: Trends Pharmacol. Sci.
– volume: 9
  start-page: 430
  year: 2004
  end-page: 431
  publication-title: Drug Discovery Today
– volume: 11
  start-page: 1521
  year: 1998
  end-page: 1528
  publication-title: Chem. Res. Toxicol.
– volume: 134
  start-page: 232
  year: 2019
  publication-title: Blood
– volume: 18
  start-page: 949
  year: 2019
  end-page: 963
  publication-title: Nat. Rev. Drug Discovery
– year: 2021
  publication-title: Blood
– volume: 134
  start-page: 2703
  year: 2019
  publication-title: Blood
– volume: 25
  start-page: 324
  year: 1965
  end-page: 337
  publication-title: Br. J. Pharmacol. Chemother.
– volume: 61
  start-page: 6685
  year: 2018
  end-page: 6704
  publication-title: J. Med. Chem.
– volume: 31
  start-page: 29
  year: 2019
  end-page: 34
  publication-title: Drug Discovery Today Technol.
– volume: 535
  start-page: 252
  year: 2016
  end-page: 257
  publication-title: Nature
– volume: 13
  start-page: 1508
  year: 2018
  end-page: 1512
  publication-title: ChemMedChem
– volume: 110
  start-page: 335
  year: 2012
  end-page: 348
  publication-title: J. Neurooncol.
– year: 2017
– volume: 140
  start-page: 16428
  year: 2018
  end-page: 16432
  publication-title: J. Am. Chem. Soc.
– volume: 5
  start-page: 2355
  year: 2014
  end-page: 2371
  publication-title: Oncotarget
– volume: 29
  start-page: 1555
  year: 2019
  end-page: 1564
  publication-title: Bioorg. Med. Chem. Lett.
– volume: 521
  start-page: 833
  year: 2020
  end-page: 839
  publication-title: Biochem. Biophys. Res. Commun.
– volume: 166
  start-page: 65
  year: 2019
  end-page: 74
  publication-title: Eur. J. Med. Chem.
– volume: 50
  start-page: 111
  year: 2019
  end-page: 119
  publication-title: Curr. Opin. Chem. Biol.
– ident: e_1_2_6_5_1
  doi: 10.1021/acs.jmedchem.0c01313
– ident: e_1_2_6_37_1
  doi: 10.18632/oncotarget.1659
– ident: e_1_2_6_20_1
  doi: 10.1182/blood-2019-123966
– ident: e_1_2_6_23_1
– ident: e_1_2_6_11_1
  doi: 10.1016/j.chembiol.2015.05.009
– ident: e_1_2_6_21_1
  doi: 10.1016/j.ejmech.2019.01.023
– ident: e_1_2_6_34_1
– ident: e_1_2_6_6_1
  doi: 10.1038/s41573-019-0047-y
– ident: e_1_2_6_16_1
  doi: 10.1002/cmdc.201800271
– ident: e_1_2_6_17_1
  doi: 10.1182/blood-2015-02-628669
– ident: e_1_2_6_33_1
  doi: 10.1021/acs.bioconjchem.0c00507
– ident: e_1_2_6_4_1
  doi: 10.1016/j.ddtec.2019.02.004
– ident: e_1_2_6_36_1
  doi: 10.1016/j.bmcl.2019.04.030
– ident: e_1_2_6_31_1
  doi: 10.1021/jacs.8b10320
– ident: e_1_2_6_13_1
  doi: 10.1016/j.ddtec.2019.04.001
– ident: e_1_2_6_30_1
  doi: 10.1021/acs.jmedchem.8b00506
– ident: e_1_2_6_22_1
– ident: e_1_2_6_26_1
  doi: 10.1021/acs.jmedchem.7b01406
– ident: e_1_2_6_2_1
  doi: 10.1016/j.tips.2020.02.006
– ident: e_1_2_6_14_1
  doi: 10.1111/j.1476-5381.1965.tb02054.x
– ident: e_1_2_6_35_1
  doi: 10.1038/nchembio.2329
– ident: e_1_2_6_18_1
  doi: 10.1182/blood-2019-127892
– ident: e_1_2_6_25_1
– ident: e_1_2_6_15_1
  doi: 10.1111/j.1476-5381.1965.tb02053.x
– ident: e_1_2_6_7_1
  doi: 10.1182/blood.2020006846
– ident: e_1_2_6_3_1
  doi: 10.1038/s41589-019-0362-y
– ident: e_1_2_6_9_1
  doi: 10.1016/j.cbpa.2019.02.022
– ident: e_1_2_6_12_1
  doi: 10.1126/science.aab1433
– ident: e_1_2_6_1_1
  doi: 10.1126/science.1177319
– ident: e_1_2_6_10_1
  doi: 10.1073/pnas.141230798
– ident: e_1_2_6_27_1
  doi: 10.1016/S1359-6446(04)03069-7
– ident: e_1_2_6_32_1
  doi: 10.1016/j.bbrc.2019.11.007
– ident: e_1_2_6_8_1
  doi: 10.1126/science.aat0572
– ident: e_1_2_6_29_1
  doi: 10.1007/s11060-012-0978-1
– ident: e_1_2_6_19_1
  doi: 10.1038/nature18611
– ident: e_1_2_6_24_1
  doi: 10.1038/nature13527
– ident: e_1_2_6_28_1
  doi: 10.1021/tx9801817
– volume: 348
  start-page: 1376
  year: 2015
  ident: WOS:000356449500055
  article-title: Phthalimide conjugation as a strategy for in vivo target protein degradation
  publication-title: SCIENCE
  doi: 10.1126/science.aab1433
– volume: 61
  start-page: 6685
  year: 2018
  ident: WOS:000441484300015
  article-title: Discovery of QCA570 as an Exceptionally Potent and Efficacious Proteolysis Targeting Chimera (PROTAC) Degrader of the Bromodomain and Extra-Terminal (BET) Proteins Capable of Inducing Complete and Durable Tumor Regression
  publication-title: JOURNAL OF MEDICINAL CHEMISTRY
  doi: 10.1021/acs.jmedchem.8b00506
– volume: 362
  start-page: 558
  year: 2018
  ident: WOS:000450460000038
  article-title: Defining the human C2H2 zinc finger degrome targeted by thalidomide analogs through CRBN
  publication-title: SCIENCE
  doi: 10.1126/science.aat0572
– volume: 126
  start-page: 779
  year: 2015
  ident: WOS:000360519600013
  article-title: CC-122, a pleiotropic pathway modifier, mimics an interferon response and has antitumor activity in DLBCL
  publication-title: BLOOD
  doi: 10.1182/blood-2015-02-628669
– volume: 134
  year: 2019
  ident: WOS:000577160406084
  article-title: CC-90009, a Novel Cereblon E3 Ligase Modulator, Targets GSPT1 for Degradation to Induce Potent Tumoricidal Activity Against Acute Myeloid Leukemia (AML)
  publication-title: BLOOD
  doi: 10.1182/blood-2019-127892
– volume: 29
  start-page: 1555
  year: 2019
  ident: WOS:000468145300002
  article-title: Proteolysis targeting chimeras (PROTACs) in 'beyond rule-of-five' chemical space: Recent progress and future challenges
  publication-title: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
  doi: 10.1016/j.bmcl.2019.04.030
– volume: 18
  start-page: 949
  year: 2019
  ident: WOS:000499643000015
  article-title: Targeted protein degradation: expanding the toolbox
  publication-title: NATURE REVIEWS DRUG DISCOVERY
  doi: 10.1038/s41573-019-0047-y
– volume: 41
  start-page: 305
  year: 2020
  ident: WOS:000527560400005
  article-title: Critical Assessment of Targeted Protein Degradation as a Research Tool and Pharmacological Modality
  publication-title: TRENDS IN PHARMACOLOGICAL SCIENCES
  doi: 10.1016/j.tips.2020.02.006
– year: 2019
  ident: 000718932200001.25
  publication-title: Molecular Operating Environment (MOE), 2019.01.
– volume: 61
  start-page: 918
  year: 2018
  ident: WOS:000425063400020
  article-title: Demonstrating In-Cell Target Engagement Using a Pirin Protein Degradation Probe (CCT367766)
  publication-title: JOURNAL OF MEDICINAL CHEMISTRY
  doi: 10.1021/acs.jmedchem.7b01406
– volume: 5
  start-page: 2355
  year: 2014
  ident: WOS:000336966600003
  article-title: Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma
  publication-title: ONCOTARGET
– volume: 50
  start-page: 111
  year: 2019
  ident: WOS:000473839100014
  article-title: Targeted protein degradation: elements of PROTAC design
  publication-title: CURRENT OPINION IN CHEMICAL BIOLOGY
  doi: 10.1016/j.cbpa.2019.02.022
– volume: 166
  start-page: 65
  year: 2019
  ident: WOS:000461402400006
  article-title: A novel cereblon modulator for targeted protein degradation
  publication-title: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
  doi: 10.1016/j.ejmech.2019.01.023
– volume: 11
  start-page: 1521
  year: 1998
  ident: WOS:000077737800019
  article-title: Chiral inversion and hydrolysis of thalidomide: Mechanisms and catalysis by bases and serum albumin, and chiral stability of teratogenic metabolites
  publication-title: CHEMICAL RESEARCH IN TOXICOLOGY
– volume: 25
  start-page: 324
  year: 1965
  ident: WOS:A19656906900005
  article-title: METABOLISM OF THALIDOMIDE - SPONTANEOUS HYDROLYSIS OF THALIDOMIDE IN SOLUTION
  publication-title: BRITISH JOURNAL OF PHARMACOLOGY AND CHEMOTHERAPY
– volume: 521
  start-page: 833
  year: 2020
  ident: WOS:000507487200003
  article-title: Protein targeting chimeric molecules specific for dual bromodomain 4 (BRD4) and Polo-like kinase 1 (PLK1) proteins in acute myeloid leukemia cells
  publication-title: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
  doi: 10.1016/j.bbrc.2019.11.007
– volume: 138
  start-page: 2313
  year: 2021
  ident: WOS:000744210800007
  article-title: Degradation of Janus kinases in CRLF2-rearranged acute lymphoblastic leukemia
  publication-title: BLOOD
  doi: 10.1182/blood.2020006846
– volume: 31
  start-page: 2564
  year: 2020
  ident: WOS:000592907700013
  article-title: Development of BODIPY FL Thalidomide As a High-Affinity Fluorescent Probe for Cereblon in a Time-Resolved Fluorescence Resonance Energy Transfer Assay
  publication-title: BIOCONJUGATE CHEMISTRY
  doi: 10.1021/acs.bioconjchem.0c00507
– year: 2021
  ident: 000718932200001.23
  publication-title: Compounds for targeted degradation of BRD9
– volume: 13
  start-page: 1508
  year: 2018
  ident: WOS:000441432700002
  article-title: Efficient Synthesis of Immunomodulatory Drug Analogues Enables Exploration of Structure-Degradation Relationships
  publication-title: CHEMMEDCHEM
  doi: 10.1002/cmdc.201800271
– volume: 13
  start-page: 514
  year: 2017
  ident: WOS:000399004000012
  article-title: Structural basis of PROTAC cooperative recognition for selective protein degradation
  publication-title: NATURE CHEMICAL BIOLOGY
  doi: 10.1038/NCHEMBIO.2329
– volume: 535
  start-page: 252
  year: 2016
  ident: WOS:000379912600050
  article-title: A novel cereblon modulator recruits GSPT1 to the CRL4CRBN ubiquitin ligase
  publication-title: NATURE
  doi: 10.1038/nature18611
– volume: 31
  start-page: 29
  year: 2019
  ident: MEDLINE:31200856
  article-title: Cereblon modulators: Low molecular weight inducers of protein degradation.
  publication-title: Drug discovery today. Technologies
  doi: 10.1016/j.ddtec.2019.02.004
– volume: 64
  start-page: 7296
  year: 2021
  ident: WOS:000662187100013
  article-title: Identification of Potent, Selective, and Orally Bioavailable Small-Molecule GSPT1/2 Degraders from a Focused Library of Cereblon Modulators
  publication-title: JOURNAL OF MEDICINAL CHEMISTRY
  doi: 10.1021/acs.jmedchem.0c01313
– volume: 15
  start-page: 937
  year: 2019
  ident: WOS:000487965400007
  article-title: Development of targeted protein degradation therapeutics
  publication-title: NATURE CHEMICAL BIOLOGY
  doi: 10.1038/s41589-019-0362-y
– year: 2017
  ident: 000718932200001.22
  article-title: C3-Carbon linked glutarimide degronimers for target protein degradation
  publication-title: WO2017197046A1
– volume: 134
  year: 2019
  ident: WOS:000518218500460
  article-title: Clinical Activity of CC-90009, a Cereblon E3 Ligase Modulator and First-in-Class GSPT1 Degrader, As a Single Agent in Patients with Relapsed or Refractory Acute Myeloid Leukemia (R/R AML): First Results from a Phase I Dose-Finding Study
  publication-title: BLOOD
  doi: 10.1182/blood-2019-123966
– volume: 512
  start-page: 49
  year: 2014
  ident: WOS:000339908000028
  article-title: Structure of the DDBI-CRBN E3 ubiquitin ligase in complex with thalidomide
  publication-title: NATURE
  doi: 10.1038/nature13527
– volume: 22
  start-page: 755
  year: 2015
  ident: WOS:000358411900009
  article-title: Hijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4
  publication-title: CHEMISTRY & BIOLOGY
  doi: 10.1016/j.chembiol.2015.05.009
– volume: 9
  start-page: 430
  year: 2004
  ident: WOS:000221394000005
  article-title: Ligand efficiency: a useful metric for lead selection
  publication-title: DRUG DISCOVERY TODAY
– volume: 140
  start-page: 16428
  year: 2018
  ident: WOS:000452693800010
  article-title: Enhancing Antiproliferative Activity and Selectivity of a FLT-3 Inhibitor by Proteolysis Targeting Chimera Conversion
  publication-title: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
  doi: 10.1021/jacs.8b10320
– volume: 25
  start-page: 338
  year: 1965
  ident: WOS:A19656906900006
  article-title: METABOLISM OF THALIDOMIDE - FATE OF THALIDOMIDE AND SOME OF ITS HYDROLYSIS PRODUCTS IN VARIOUS SPECIES
  publication-title: BRITISH JOURNAL OF PHARMACOLOGY AND CHEMOTHERAPY
– volume: 31
  start-page: 43
  year: 2019
  ident: MEDLINE:31200858
  article-title: Small-molecule PROTAC degraders of the Bromodomain and Extra Terminal (BET) proteins - A review.
  publication-title: Drug discovery today. Technologies
  doi: 10.1016/j.ddtec.2019.04.001
– volume: 327
  start-page: 1345
  year: 2010
  ident: WOS:000275418700032
  article-title: Identification of a Primary Target of Thalidomide Teratogenicity
  publication-title: SCIENCE
  doi: 10.1126/science.1177319
– volume: 110
  start-page: 335
  year: 2012
  ident: WOS:000311208300004
  article-title: HD-MB03 is a novel Group 3 medulloblastoma model demonstrating sensitivity to histone deacetylase inhibitor treatment
  publication-title: JOURNAL OF NEURO-ONCOLOGY
  doi: 10.1007/s11060-012-0978-1
– volume: 98
  start-page: 8554
  year: 2001
  ident: WOS:000169967000064
  article-title: Protacs: Chimeric molecules that target proteins to the Skp1-Cullin-F box complex for ubiquitination and degradation
  publication-title: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
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Snippet Targeting cereblon (CRBN) is currently one of the most frequently reported proteolysis‐targeting chimera (PROTAC) approaches, owing to favorable drug‐like...
Targeting cereblon (CRBN) is currently one of the most frequently reported proteolysis-targeting chimera (PROTAC) approaches, owing to favorable drug-like...
Targeting cereblon (CRBN) is currently one of the most frequently reported proteolysis-targeting chimera (PROTAC) approaches, owing to favorable drug-like...
Source Web of Science
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hal
proquest
pubmed
webofscience
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wiley
SourceType Open Access Repository
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StartPage 26663
SubjectTerms Acute myeloid leukemia
Adaptor Proteins, Signal Transducing - chemistry
Binders
Body fluids
cereblon
Chemistry
Chemistry, Multidisciplinary
Human health and pathology
Humans
Hydrolysis
IMiD
Immunomodulation
Leukemia
Life Sciences
Ligands
Myeloid leukemia
phenyl glutarimide
Physical Sciences
Piperidones - chemistry
PROTAC
Proteolysis
Science & Technology
Ubiquitin-Protein Ligases - chemistry
Title Phenyl‐Glutarimides: Alternative Cereblon Binders for the Design of PROTACs
URI https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fanie.202108848
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https://www.ncbi.nlm.nih.gov/pubmed/34614283
https://www.proquest.com/docview/2606919595
https://www.proquest.com/docview/2580014787
https://u-picardie.hal.science/hal-03720142
https://pubmed.ncbi.nlm.nih.gov/PMC8648984
Volume 60
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