Stabilization of protein-protein interactions in drug discovery

Introduction: PPIs are involved in every disease and specific modulation of these PPIs with small molecules would significantly improve our prospects of developing therapeutic agents. Both industry and academia have engaged in the identification and use of PPI inhibitors. However in comparison, the...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Expert opinion on drug discovery Jg. 12; H. 9; S. 925 - 940
Hauptverfasser: Andrei, Sebastian A., Sijbesma, Eline, Hann, Michael, Davis, Jeremy, O'Mahony, Gavin, Perry, Matthew W. D., Karawajczyk, Anna, Eickhoff, Jan, Brunsveld, Luc, Doveston, Richard G., Milroy, Lech-Gustav, Ottmann, Christian
Format: Journal Article
Sprache:Englisch
Veröffentlicht: England Taylor & Francis 02.09.2017
Schlagworte:
Biological Products - pharmacology
Chemical biology
Drug Design
Drug Discovery - methods
druggable genome
Humans
medicinal chemistry
Pharmaceutical Preparations - chemical synthesis
Pharmaceutical Preparations - chemistry
Pharmaceutical Preparations - metabolism
PPI stabilization
PPIs
Protein Binding
Protein Stability
Proteins - metabolism
Small Molecule Libraries
small molecules
tool compounds
X-ray crystallography
Chemical biology
X-ray crystallography
druggable genome
tool compounds
PPI stabilization
medicinal chemistry
small molecules
PPIs
ISSN:1746-0441, 1746-045X, 1746-045X
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Abstract Introduction: PPIs are involved in every disease and specific modulation of these PPIs with small molecules would significantly improve our prospects of developing therapeutic agents. Both industry and academia have engaged in the identification and use of PPI inhibitors. However in comparison, the opposite strategy of employing small-molecule stabilizers of PPIs is underrepresented in drug discovery. Areas covered: PPI stabilization has not been exploited in a systematic manner. Rather, this concept validated by a number of therapeutically used natural products like rapamycin and paclitaxel has been shown retrospectively to be the basis of the activity of synthetic molecules originating from drug discovery projects among them lenalidomide and tafamidis. Here, the authors cover the growing number of synthetic small-molecule PPI stabilizers to advocate for a stronger consideration of this as a drug discovery approach. Expert opinion: Both the natural products and the growing number of synthetic molecules show that PPI stabilization is a viable strategy for drug discovery. There is certainly a significant challenge to adapt compound libraries, screening techniques and downstream methodologies to identify, characterize and optimize PPI stabilizers, but the examples of molecules reviewed here in our opinion justify these efforts.
AbstractList Introduction: PPIs are involved in every disease and specific modulation of these PPIs with small molecules would significantly improve our prospects of developing therapeutic agents. Both industry and academia have engaged in the identification and use of PPI inhibitors. However in comparison, the opposite strategy of employing small-molecule stabilizers of PPIs is underrepresented in drug discovery. Areas covered: PPI stabilization has not been exploited in a systematic manner. Rather, this concept validated by a number of therapeutically used natural products like rapamycin and paclitaxel has been shown retrospectively to be the basis of the activity of synthetic molecules originating from drug discovery projects among them lenalidomide and tafamidis. Here, the authors cover the growing number of synthetic small-molecule PPI stabilizers to advocate for a stronger consideration of this as a drug discovery approach. Expert opinion: Both the natural products and the growing number of synthetic molecules show that PPI stabilization is a viable strategy for drug discovery. There is certainly a significant challenge to adapt compound libraries, screening techniques and downstream methodologies to identify, characterize and optimize PPI stabilizers, but the examples of molecules reviewed here in our opinion justify these efforts.
PPIs are involved in every disease and specific modulation of these PPIs with small molecules would significantly improve our prospects of developing therapeutic agents. Both industry and academia have engaged in the identification and use of PPI inhibitors. However in comparison, the opposite strategy of employing small-molecule stabilizers of PPIs is underrepresented in drug discovery. Areas covered: PPI stabilization has not been exploited in a systematic manner. Rather, this concept validated by a number of therapeutically used natural products like rapamycin and paclitaxel has been shown retrospectively to be the basis of the activity of synthetic molecules originating from drug discovery projects among them lenalidomide and tafamidis. Here, the authors cover the growing number of synthetic small-molecule PPI stabilizers to advocate for a stronger consideration of this as a drug discovery approach. Expert opinion: Both the natural products and the growing number of synthetic molecules show that PPI stabilization is a viable strategy for drug discovery. There is certainly a significant challenge to adapt compound libraries, screening techniques and downstream methodologies to identify, characterize and optimize PPI stabilizers, but the examples of molecules reviewed here in our opinion justify these efforts.INTRODUCTIONPPIs are involved in every disease and specific modulation of these PPIs with small molecules would significantly improve our prospects of developing therapeutic agents. Both industry and academia have engaged in the identification and use of PPI inhibitors. However in comparison, the opposite strategy of employing small-molecule stabilizers of PPIs is underrepresented in drug discovery. Areas covered: PPI stabilization has not been exploited in a systematic manner. Rather, this concept validated by a number of therapeutically used natural products like rapamycin and paclitaxel has been shown retrospectively to be the basis of the activity of synthetic molecules originating from drug discovery projects among them lenalidomide and tafamidis. Here, the authors cover the growing number of synthetic small-molecule PPI stabilizers to advocate for a stronger consideration of this as a drug discovery approach. Expert opinion: Both the natural products and the growing number of synthetic molecules show that PPI stabilization is a viable strategy for drug discovery. There is certainly a significant challenge to adapt compound libraries, screening techniques and downstream methodologies to identify, characterize and optimize PPI stabilizers, but the examples of molecules reviewed here in our opinion justify these efforts.
PPIs are involved in every disease and specific modulation of these PPIs with small molecules would significantly improve our prospects of developing therapeutic agents. Both industry and academia have engaged in the identification and use of PPI inhibitors. However in comparison, the opposite strategy of employing small-molecule stabilizers of PPIs is underrepresented in drug discovery. Areas covered: PPI stabilization has not been exploited in a systematic manner. Rather, this concept validated by a number of therapeutically used natural products like rapamycin and paclitaxel has been shown retrospectively to be the basis of the activity of synthetic molecules originating from drug discovery projects among them lenalidomide and tafamidis. Here, the authors cover the growing number of synthetic small-molecule PPI stabilizers to advocate for a stronger consideration of this as a drug discovery approach. Expert opinion: Both the natural products and the growing number of synthetic molecules show that PPI stabilization is a viable strategy for drug discovery. There is certainly a significant challenge to adapt compound libraries, screening techniques and downstream methodologies to identify, characterize and optimize PPI stabilizers, but the examples of molecules reviewed here in our opinion justify these efforts.
Author Sijbesma, Eline
Eickhoff, Jan
Brunsveld, Luc
Milroy, Lech-Gustav
Doveston, Richard G.
Ottmann, Christian
Davis, Jeremy
Andrei, Sebastian A.
Hann, Michael
Perry, Matthew W. D.
O'Mahony, Gavin
Karawajczyk, Anna
Author_xml – sequence: 1
  givenname: Sebastian A.
  surname: Andrei
  fullname: Andrei, Sebastian A.
  organization: Laboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of Technology
– sequence: 2
  givenname: Eline
  surname: Sijbesma
  fullname: Sijbesma, Eline
  organization: Laboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of Technology
– sequence: 3
  givenname: Michael
  surname: Hann
  fullname: Hann, Michael
  organization: Platform Technology and Science, Medicines Research Centre, GlaxoSmithKline R&D
– sequence: 4
  givenname: Jeremy
  surname: Davis
  fullname: Davis, Jeremy
  organization: Department of Chemistry, UCB Celltech
– sequence: 5
  givenname: Gavin
  surname: O'Mahony
  fullname: O'Mahony, Gavin
  organization: CVMD Medicinal Chemistry, Innovative Medicines and Early Development, AstraZeneca Gothenburg
– sequence: 6
  givenname: Matthew W. D.
  surname: Perry
  fullname: Perry, Matthew W. D.
  organization: RIA Medicinal Chemistry, Innovative Medicines and Early Development, AstraZeneca Gothenburg
– sequence: 7
  givenname: Anna
  surname: Karawajczyk
  fullname: Karawajczyk, Anna
  organization: Medicinal Chemistry, Taros Chemicals GmbH & Co. KG
– sequence: 8
  givenname: Jan
  surname: Eickhoff
  fullname: Eickhoff, Jan
  organization: Assay development & screening, Lead Discovery Center GmbH
– sequence: 9
  givenname: Luc
  surname: Brunsveld
  fullname: Brunsveld, Luc
  organization: Laboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of Technology
– sequence: 10
  givenname: Richard G.
  surname: Doveston
  fullname: Doveston, Richard G.
  organization: Laboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of Technology
– sequence: 11
  givenname: Lech-Gustav
  surname: Milroy
  fullname: Milroy, Lech-Gustav
  organization: Laboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of Technology
– sequence: 12
  givenname: Christian
  surname: Ottmann
  fullname: Ottmann, Christian
  email: C.Ottmann@tue.nl
  organization: Department of Chemistry, University of Duisburg-Essen
BackLink https://www.ncbi.nlm.nih.gov/pubmed/28695752$$D View this record in MEDLINE/PubMed
BookMark eNqFkMtOxCAUhokZ41z0ETRduukIFArEhZqJt2QSF87CHaEtGExbRqCa8entOJeFC10dOHz_yeEbg0HrWg3AKYJTBDm8QIzkkBA0xRCxKcpInkN-AEbrfgoJfRnszwQNwTiENwhpxrPsCAwxzwVlFI_A1XNUha3tl4rWtYkzydK7qG2bbmti26i9KtfPob8kle9ek8qG0n1ovzoGh0bVQZ9s6wQs7m4Xs4d0_nT_OLuZpyVhIqaca80ZhowSzQXEuEA5VowVWmCDdKYgERWmvKAFIcaoDFJlmKkqVRohYDYB55ux_VbvnQ5RNv0Guq5Vq10XJBKIiRxSKnr0bIt2RaMrufS2UX4ld3_uAboBSu9C8NrsEQTl2q3cuZVrt3Lrts9d_sqVNv5oi17Z-t_09SZtW-N8oz6drysZ1ap23njVljbI7O8R3_GSkdQ
CitedBy_id crossref_primary_10_1016_j_chmed_2025_01_001
crossref_primary_10_1021_acscentsci_3c00395
crossref_primary_10_1016_j_molcel_2019_07_017
crossref_primary_10_1039_D1SC01450A
crossref_primary_10_1002_ange_201806584
crossref_primary_10_3762_bjoc_14_267
crossref_primary_10_1021_jacs_3c12389
crossref_primary_10_1080_08927022_2022_2080824
crossref_primary_10_1002_cmdc_202401017
crossref_primary_10_1007_s40203_023_00172_2
crossref_primary_10_1016_j_bmcl_2019_07_027
crossref_primary_10_1016_j_cbpa_2019_07_003
crossref_primary_10_1038_s41467_024_49982_8
crossref_primary_10_1016_j_jcrysgro_2020_125591
crossref_primary_10_1080_17460441_2021_1969359
crossref_primary_10_1002_anie_202001578
crossref_primary_10_1016_j_semcdb_2019_12_009
crossref_primary_10_1039_D1SC02120F
crossref_primary_10_1002_anie_201914396
crossref_primary_10_1016_j_drudis_2021_01_005
crossref_primary_10_1002_anie_202008585
crossref_primary_10_1002_anie_202308004
crossref_primary_10_1002_advs_202508543
crossref_primary_10_1080_17460441_2023_2218641
crossref_primary_10_1038_s41598_022_12105_8
crossref_primary_10_1021_jacs_8b09618
crossref_primary_10_1039_D2CS00197G
crossref_primary_10_1038_s41467_024_50349_2
crossref_primary_10_1038_s41467_025_61176_4
crossref_primary_10_1080_17460441_2018_1430763
crossref_primary_10_1186_s13321_025_01077_2
crossref_primary_10_1007_s42452_025_07155_2
crossref_primary_10_1080_07391102_2020_1860828
crossref_primary_10_1007_s00249_025_01763_x
crossref_primary_10_3389_fmolb_2020_00180
crossref_primary_10_1016_j_chembiol_2024_08_004
crossref_primary_10_1021_acscentsci_2c01449
crossref_primary_10_1007_s00044_024_03342_9
crossref_primary_10_1128_JVI_00983_20
crossref_primary_10_1002_jcb_30433
crossref_primary_10_3390_molecules29122779
crossref_primary_10_1002_ange_201914396
crossref_primary_10_1016_j_chembiol_2020_11_010
crossref_primary_10_1002_1873_3468_13017
crossref_primary_10_1016_j_cbpa_2019_02_012
crossref_primary_10_1049_syb2_12019
crossref_primary_10_1002_ange_202008585
crossref_primary_10_1002_chem_201904523
crossref_primary_10_1038_s41531_021_00230_6
crossref_primary_10_3390_molecules24132415
crossref_primary_10_1021_jacs_7b07939
crossref_primary_10_1039_D1SC06426F
crossref_primary_10_1042_BST20201058
crossref_primary_10_1042_BST20200482
crossref_primary_10_1016_j_bbapap_2020_140405
crossref_primary_10_1016_j_bbrc_2019_12_037
crossref_primary_10_1021_acs_jmedchem_5c00220
crossref_primary_10_1002_anie_201806584
crossref_primary_10_1039_D0SC05694D
crossref_primary_10_1002_slct_202502605
crossref_primary_10_1016_j_bbagen_2020_129730
crossref_primary_10_3390_cells14181449
crossref_primary_10_1038_s41589_020_0557_2
crossref_primary_10_1039_C8SC05242E
crossref_primary_10_1016_j_cell_2024_03_027
crossref_primary_10_1021_jacs_8b11658
crossref_primary_10_1002_cbic_202400214
crossref_primary_10_1021_acscentsci_3c00003
crossref_primary_10_1038_s41586_020_2117_z
crossref_primary_10_1016_j_drudis_2023_103670
crossref_primary_10_1038_s41573_020_0086_4
crossref_primary_10_1002_cbic_201900288
crossref_primary_10_1016_j_chembiol_2024_03_012
crossref_primary_10_1038_s41579_019_0225_2
crossref_primary_10_1038_s41392_024_02036_3
crossref_primary_10_1080_15622975_2021_1925585
crossref_primary_10_1002_cbic_202300636
crossref_primary_10_1002_cmdc_201900341
crossref_primary_10_1016_j_apsb_2023_07_016
crossref_primary_10_14814_phy2_14505
crossref_primary_10_1021_jacs_0c02151
crossref_primary_10_1002_cbic_201800716
crossref_primary_10_1080_08927022_2019_1593977
crossref_primary_10_1093_cvr_cvaa249
crossref_primary_10_1002_ange_202001578
crossref_primary_10_12677_JAPC_2019_81002
crossref_primary_10_1515_hsz_2019_0405
crossref_primary_10_3390_biom11030377
crossref_primary_10_1038_s41467_024_45002_x
crossref_primary_10_3390_ijms21175962
crossref_primary_10_1002_1873_3468_13993
crossref_primary_10_1038_s41467_019_09358_9
crossref_primary_10_3390_biom12040594
crossref_primary_10_1002_ange_202308004
crossref_primary_10_1038_s41467_020_17741_0
Cites_doi 10.1021/jm0708735
10.1016/j.chembiol.2007.10.012
10.1038/nrm1680
10.1124/pr.58.4.4
10.1242/jcs.00194
10.1038/nature10180
10.1007/s004410051218
10.1002/prot.21296
10.1038/ncomms2750
10.1021/ja908562q
10.1371/journal.pone.0076676
10.1073/pnas.0408277102
10.1002/anie.200802915
10.1074/jbc.M111394200
10.1210/endo-108-4-1353
10.1016/j.chembiol.2009.03.008
10.1002/chem.201103761
10.1002/anie.201507976
10.1016/S0039-128X(00)00178-1
10.1126/science.1079589
10.1038/nchembio.2210
10.1016/j.jmb.2007.05.056
10.1007/s00109-007-0301-3
10.1016/0092-8674(95)90346-1
10.1002/pro.5560031010
10.1074/jbc.M205076200
10.1073/pnas.2233339100
10.1038/labinvest.3700059
10.1038/nature12751
10.1038/nature10673
10.1073/pnas.0510596103
10.1016/j.cell.2011.08.017
10.1210/me.2006-0524
10.1016/j.drudis.2015.09.011
10.1016/j.sbi.2009.12.009
10.1016/S0968-0896(99)00066-8
10.1038/nature17679
10.1002/anie.200907203
10.1152/ajplung.1996.271.5.L775
10.1038/415813a
10.1074/jbc.270.8.3463
10.1038/nchembio.1412
10.1038/nature08231
10.1152/physrev.00018.2013
10.1073/pnas.91.5.1781
10.1073/pnas.74.12.5613
10.1038/nature16979
10.1016/j.cell.2011.05.039
10.2174/0929867033457908
10.1371/journal.pone.0110884
10.2174/0929867305666220314194045
10.1016/j.chembiol.2013.03.015
10.2174/156652408785747942
10.1074/jbc.275.7.5163
10.1016/S0960-894X(98)00696-9
10.1038/ncomms10787
10.1124/pr.56.2.6
10.1016/S0896-6273(00)00094-5
10.1093/jnci/90.20.1559
10.1021/bi800636q
10.1006/bbrc.2000.3104
10.1073/pnas.1131855100
10.1073/pnas.93.26.15051
10.1523/JNEUROSCI.2567-05.2005
10.1073/pnas.1832879100
10.1021/jm0002836
10.1016/j.chembiol.2012.05.011
10.1073/pnas.0913660107
10.1016/0361-9230(95)00040-2
10.1007/BF00446784
10.1111/j.1749-6632.1995.tb31373.x
10.1021/jm800435s
10.2174/1568009043332998
10.1124/mol.59.3.462
10.1016/j.drudis.2014.08.005
10.1128/JVI.01424-08
10.1586/14737159.8.2.179
10.1017/S0031182010000259
10.1021/ar020073i
10.1006/jmbi.1997.1529
10.1038/nature18611
10.1016/j.cell.2013.02.014
10.1074/jbc.M608410200
10.1016/j.mad.2004.08.006
10.1001/archinte.165.12.1425
10.1038/ncomms2017
10.1126/science.1092472
10.1038/74082
10.1016/j.chembiol.2005.02.011
10.1016/S0021-9258(17)36545-6
10.1021/ja211708z
10.1186/s12936-015-0834-9
10.1073/pnas.1220809110
10.1002/anie.200801156
10.1073/pnas.1203789109
10.1021/bi7021624
10.1016/S1734-1140(09)70018-0
10.18632/oncotarget.8730
10.2741/3954
10.1021/cr400698c
10.1074/jbc.M402195200
10.1124/pr.58.4.2
10.1016/j.pbiomolbio.2015.05.002
10.1016/j.chembiol.2010.06.010
10.1038/nrc3239
10.1530/jrf.0.0130101
10.1002/anie.200801010
10.1124/mol.114.093286
10.1038/nrm2026
10.1016/0014-2999(94)90442-1
10.1016/S0022-3565(25)13281-3
10.1021/jm00383a010
10.7164/antibiotics.46.741
10.1021/ja030294z
10.1073/pnas.241410198
10.1038/417245a
10.1074/jbc.R500017200
10.1038/nrd3531
10.1200/JCO.2007.14.9401
10.1146/annurev-biophys-042910-155359
10.1073/pnas.1220253110
10.1128/AAC.30.1.110
10.1126/science.274.5289.948
10.1126/science.1261962
10.1021/jm030347n
10.1038/nrd2056
10.1099/0022-1317-72-2-431
10.1046/j.1365-313X.1997.12020441.x
10.1073/pnas.1008255107
10.1021/jm901062p
10.1073/pnas.0407189102
10.1007/978-1-61779-788-0_10
10.1073/pnas.0805326105
10.1002/anie.200351179
10.1021/jm010257n
10.1021/ja993309v
10.1248/cpb.38.2960
10.1677/joe.0.0750305
10.1158/0008-5472.CAN-12-4501
10.1529/biophysj.104.047753
10.1146/annurev.biochem.75.101304.123901
10.1016/S0968-0896(98)00130-8
10.1038/nrd1551
10.1016/S0022-2836(03)00306-1
10.1073/pnas.1121005109
10.1073/pnas.151244398
10.1074/jbc.M111.308403
10.1101/pdb.prot4947
10.1002/jlac.19385330105
10.1073/pnas.1107906108
10.1016/j.bbrc.2004.07.096
10.1126/science.1251915
10.1126/science.3018924
10.1038/nsmb.1855
ContentType Journal Article
Copyright 2017 The Author(s). Published by nforma UK Limited, trading as Taylor & Francis Group 2017
Copyright_xml – notice: 2017 The Author(s). Published by nforma UK Limited, trading as Taylor & Francis Group 2017
DBID 0YH
AAYXX
CITATION
CGR
CUY
CVF
ECM
EIF
NPM
7X8
DOI 10.1080/17460441.2017.1346608
DatabaseName Taylor & Francis Open Access
CrossRef
Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
MEDLINE - Academic
DatabaseTitle CrossRef
MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
MEDLINE - Academic
DatabaseTitleList
MEDLINE - Academic
MEDLINE
Database_xml – sequence: 1
  dbid: NPM
  name: PubMed
  url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 2
  dbid: 0YH
  name: Taylor & Francis Open Access
  url: https://www.tandfonline.com
  sourceTypes: Publisher
– sequence: 3
  dbid: 7X8
  name: MEDLINE - Academic
  url: https://search.proquest.com/medline
  sourceTypes: Aggregation Database
DeliveryMethod fulltext_linktorsrc
Discipline Pharmacy, Therapeutics, & Pharmacology
EISSN 1746-045X
EndPage 940
ExternalDocumentID 28695752
10_1080_17460441_2017_1346608
1346608
Genre Review
Research Support, Non-U.S. Gov't
Journal Article
GrantInformation_xml – fundername: Nederlandse Organisatie voor Wetenschappelijk Onderzoek
  grantid: Gravity program 024.001.035
  funderid: 10.13039/501100003246
– fundername: Deutsche Forschungsgemeinschaft
  grantid: CRC 1093
  funderid: 10.13039/501100001659
– fundername: Horizon 2020 Framework Programme
  grantid: Marie Curie ITN TASPPI (675179)
  funderid: 10.13039/100010661
GroupedDBID ---
00X
03L
0R~
0YH
29G
4.4
53G
5GY
AAMIU
AAOUU
ABEIZ
ABJNI
ABLIJ
ABLKL
ABXYU
ACGFS
ACIEZ
ADCVX
ADRBQ
AECIN
AENEX
AEOZL
AFRVT
AGDLA
AGMLL
AIJEM
AIRBT
AIYSM
AIZAD
AKBVH
ALMA_UNASSIGNED_HOLDINGS
ALQZU
AQTUD
BABNJ
BLEHA
CCCUG
CS3
DKSSO
DU5
EBS
EJD
F5P
H13
HZ~
KRBQP
KSSTO
KWAYT
KYCEM
M4Z
O9-
RNANH
TASJS
TBQAZ
TDBHL
TERGH
TFDNU
TFL
TFW
TUROJ
TZHSB
V1S
~1N
AAYXX
CITATION
0BK
ABBAB
ABVAX
CGR
CUY
CVF
ECM
EIF
LJTGL
M44
NPM
7X8
ID FETCH-LOGICAL-c479t-88ee8720754e89022b162a77be92f1e3a049d258b5b44ffa305af7fddacf9903
IEDL.DBID 0YH
ISICitedReferencesCount 130
ISICitedReferencesURI http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000407431900005&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
ISSN 1746-0441
1746-045X
IngestDate Sun Nov 09 09:06:45 EST 2025
Thu Jan 02 23:09:21 EST 2025
Tue Nov 18 21:32:51 EST 2025
Sat Nov 29 07:51:29 EST 2025
Mon Oct 20 23:47:34 EDT 2025
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 9
Keywords Chemical biology
X-ray crystallography
druggable genome
tool compounds
PPI stabilization
medicinal chemistry
small molecules
PPIs
Language English
License open-access: http://creativecommons.org/licenses/by-nc-nd/4.0/: This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c479t-88ee8720754e89022b162a77be92f1e3a049d258b5b44ffa305af7fddacf9903
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
ObjectType-Review-3
content type line 23
OpenAccessLink https://www.tandfonline.com/doi/abs/10.1080/17460441.2017.1346608
PMID 28695752
PQID 1917960559
PQPubID 23479
PageCount 16
ParticipantIDs crossref_primary_10_1080_17460441_2017_1346608
proquest_miscellaneous_1917960559
informaworld_taylorfrancis_310_1080_17460441_2017_1346608
pubmed_primary_28695752
crossref_citationtrail_10_1080_17460441_2017_1346608
PublicationCentury 2000
PublicationDate 2017-09-02
PublicationDateYYYYMMDD 2017-09-02
PublicationDate_xml – month: 09
  year: 2017
  text: 2017-09-02
  day: 02
PublicationDecade 2010
PublicationPlace England
PublicationPlace_xml – name: England
PublicationTitle Expert opinion on drug discovery
PublicationTitleAlternate Expert Opin Drug Discov
PublicationYear 2017
Publisher Taylor & Francis
Publisher_xml – name: Taylor & Francis
References CIT0072
CIT0071
CIT0074
CIT0073
CIT0075
CIT0078
CIT0111
CIT0110
CIT0070
CIT0113
CIT0079
CIT0112
CIT0115
CIT0117
CIT0116
CIT0119
CIT0118
CIT0083
CIT0082
CIT0085
CIT0084
CIT0087
CIT0120
CIT0086
CIT0001
CIT0089
CIT0122
CIT0088
CIT0121
CIT0081
CIT0080
CIT0003
CIT0124
CIT0002
CIT0123
CIT0005
CIT0126
CIT0004
CIT0125
CIT0128
CIT0006
CIT0127
CIT0009
CIT0008
CIT0129
CIT0094
Pollard TD (CIT0007) 2016; 8
CIT0093
CIT0096
CIT0095
CIT0010
CIT0098
CIT0131
CIT0097
CIT0130
CIT0012
CIT0133
CIT0011
CIT0099
CIT0132
Gotti B (CIT0090) 1988; 247
CIT0092
CIT0091
CIT0014
CIT0135
CIT0013
CIT0134
CIT0016
CIT0137
CIT0015
CIT0136
CIT0018
CIT0139
CIT0017
CIT0138
CIT0019
CIT0140
CIT0021
CIT0142
CIT0020
CIT0141
CIT0023
CIT0144
CIT0022
CIT0143
Bubb MR (CIT0028) 1994; 269
CIT0025
CIT0146
CIT0024
Tanabe K (CIT0077) 1991; 51
CIT0145
CIT0027
CIT0148
CIT0026
Bai R (CIT0034) 2001; 59
CIT0147
CIT0029
CIT0149
CIT0030
CIT0151
Devor DC (CIT0045) 1996; 271
CIT0150
CIT0032
CIT0153
CIT0031
CIT0152
CIT0155
CIT0033
CIT0154
Hasinoff BB (CIT0076) 1998; 5
Basse N (CIT0037) 2010; 17
CIT0036
CIT0157
CIT0035
CIT0156
CIT0038
CIT0159
CIT0158
CIT0039
CIT0041
CIT0040
CIT0043
CIT0042
CIT0044
CIT0047
CIT0046
CIT0049
CIT0048
CIT0050
CIT0052
CIT0051
CIT0054
CIT0053
CIT0056
CIT0055
CIT0058
CIT0057
CIT0059
CIT0061
CIT0060
CIT0063
CIT0062
CIT0065
CIT0064
CIT0067
CIT0100
CIT0066
CIT0109
CIT0069
CIT0102
CIT0068
CIT0101
CIT0104
CIT0103
CIT0106
CIT0105
CIT0108
CIT0107
References_xml – ident: CIT0065
  doi: 10.1021/jm0708735
– ident: CIT0109
  doi: 10.1016/j.chembiol.2007.10.012
– ident: CIT0121
  doi: 10.1038/nrm1680
– ident: CIT0119
  doi: 10.1124/pr.58.4.4
– ident: CIT0154
  doi: 10.1242/jcs.00194
– ident: CIT0091
  doi: 10.1038/nature10180
– ident: CIT0141
  doi: 10.1007/s004410051218
– ident: CIT0145
  doi: 10.1002/prot.21296
– ident: CIT0150
  doi: 10.1038/ncomms2750
– ident: CIT0062
  doi: 10.1021/ja908562q
– ident: CIT0079
  doi: 10.1371/journal.pone.0076676
– ident: CIT0148
  doi: 10.1073/pnas.0408277102
– ident: CIT0017
  doi: 10.1002/anie.200802915
– ident: CIT0142
  doi: 10.1074/jbc.M111394200
– ident: CIT0131
  doi: 10.1210/endo-108-4-1353
– ident: CIT0123
  doi: 10.1016/j.chembiol.2009.03.008
– ident: CIT0146
  doi: 10.1002/chem.201103761
– ident: CIT0155
  doi: 10.1002/anie.201507976
– ident: CIT0138
  doi: 10.1016/S0039-128X(00)00178-1
– ident: CIT0052
  doi: 10.1126/science.1079589
– ident: CIT0118
  doi: 10.1038/nchembio.2210
– ident: CIT0011
  doi: 10.1016/j.jmb.2007.05.056
– ident: CIT0082
  doi: 10.1007/s00109-007-0301-3
– ident: CIT0147
  doi: 10.1016/0092-8674(95)90346-1
– ident: CIT0097
  doi: 10.1002/pro.5560031010
– ident: CIT0033
  doi: 10.1074/jbc.M205076200
– ident: CIT0015
  doi: 10.1073/pnas.2233339100
– ident: CIT0056
  doi: 10.1038/labinvest.3700059
– ident: CIT0116
  doi: 10.1038/nature12751
– ident: CIT0112
  doi: 10.1038/nature10673
– ident: CIT0134
  doi: 10.1073/pnas.0510596103
– ident: CIT0117
  doi: 10.1016/j.cell.2011.08.017
– ident: CIT0139
  doi: 10.1210/me.2006-0524
– ident: CIT0002
  doi: 10.1016/j.drudis.2015.09.011
– ident: CIT0058
  doi: 10.1016/j.sbi.2009.12.009
– ident: CIT0060
  doi: 10.1016/S0968-0896(99)00066-8
– ident: CIT0093
  doi: 10.1038/nature17679
– ident: CIT0143
  doi: 10.1002/anie.200907203
– volume: 271
  start-page: L775
  year: 1996
  ident: CIT0045
  publication-title: Am J Physiol Lung Cell Mol Physiol
  doi: 10.1152/ajplung.1996.271.5.L775
– ident: CIT0125
  doi: 10.1038/415813a
– ident: CIT0013
  doi: 10.1074/jbc.270.8.3463
– ident: CIT0104
  doi: 10.1038/nchembio.1412
– ident: CIT0111
  doi: 10.1038/nature08231
– ident: CIT0006
  doi: 10.1152/physrev.00018.2013
– ident: CIT0078
  doi: 10.1073/pnas.91.5.1781
– ident: CIT0025
  doi: 10.1073/pnas.74.12.5613
– ident: CIT0100
  doi: 10.1038/nature16979
– ident: CIT0103
  doi: 10.1016/j.cell.2011.05.039
– ident: CIT0043
  doi: 10.2174/0929867033457908
– ident: CIT0040
  doi: 10.1371/journal.pone.0110884
– volume: 5
  start-page: 1
  year: 1998
  ident: CIT0076
  publication-title: Curr Med Chem
  doi: 10.2174/0929867305666220314194045
– ident: CIT0159
  doi: 10.1016/j.chembiol.2013.03.015
– ident: CIT0083
  doi: 10.2174/156652408785747942
– ident: CIT0029
  doi: 10.1074/jbc.275.7.5163
– ident: CIT0067
  doi: 10.1016/S0960-894X(98)00696-9
– ident: CIT0072
  doi: 10.1038/ncomms10787
– ident: CIT0073
  doi: 10.1124/pr.56.2.6
– ident: CIT0105
  doi: 10.1016/S0896-6273(00)00094-5
– volume: 8
  year: 2016
  ident: CIT0007
  publication-title: Perspect Biol
– ident: CIT0030
  doi: 10.1093/jnci/90.20.1559
– ident: CIT0070
  doi: 10.1021/bi800636q
– ident: CIT0039
  doi: 10.1006/bbrc.2000.3104
– ident: CIT0018
  doi: 10.1073/pnas.1131855100
– ident: CIT0053
  doi: 10.1073/pnas.93.26.15051
– ident: CIT0108
  doi: 10.1523/JNEUROSCI.2567-05.2005
– ident: CIT0080
  doi: 10.1073/pnas.1832879100
– ident: CIT0106
  doi: 10.1021/jm0002836
– ident: CIT0157
  doi: 10.1016/j.chembiol.2012.05.011
– ident: CIT0087
  doi: 10.1073/pnas.0913660107
– ident: CIT0081
  doi: 10.1016/0361-9230(95)00040-2
– ident: CIT0021
  doi: 10.1007/BF00446784
– ident: CIT0132
  doi: 10.1111/j.1749-6632.1995.tb31373.x
– ident: CIT0064
  doi: 10.1021/jm800435s
– ident: CIT0008
  doi: 10.2174/1568009043332998
– volume: 59
  start-page: 462
  year: 2001
  ident: CIT0034
  publication-title: Mol Pharmacol
  doi: 10.1124/mol.59.3.462
– ident: CIT0003
  doi: 10.1016/j.drudis.2014.08.005
– ident: CIT0088
  doi: 10.1128/JVI.01424-08
– ident: CIT0044
  doi: 10.1586/14737159.8.2.179
– ident: CIT0153
  doi: 10.1017/S0031182010000259
– ident: CIT0054
  doi: 10.1021/ar020073i
– ident: CIT0026
  doi: 10.1006/jmbi.1997.1529
– ident: CIT0101
  doi: 10.1038/nature18611
– ident: CIT0156
  doi: 10.1016/j.cell.2013.02.014
– ident: CIT0127
  doi: 10.1074/jbc.M608410200
– ident: CIT0133
  doi: 10.1016/j.mad.2004.08.006
– ident: CIT0051
  doi: 10.1001/archinte.165.12.1425
– ident: CIT0047
  doi: 10.1038/ncomms2017
– ident: CIT0041
  doi: 10.1126/science.1092472
– ident: CIT0066
  doi: 10.1038/74082
– volume: 51
  start-page: 4903
  year: 1991
  ident: CIT0077
  publication-title: Cancer Res
– ident: CIT0014
  doi: 10.1016/j.chembiol.2005.02.011
– volume: 269
  start-page: 14869
  year: 1994
  ident: CIT0028
  publication-title: J Biol Chem
  doi: 10.1016/S0021-9258(17)36545-6
– ident: CIT0024
  doi: 10.1021/ja211708z
– ident: CIT0151
  doi: 10.1186/s12936-015-0834-9
– ident: CIT0158
  doi: 10.1073/pnas.1220809110
– ident: CIT0031
  doi: 10.1002/anie.200801156
– ident: CIT0020
  doi: 10.1073/pnas.1203789109
– ident: CIT0086
  doi: 10.1021/bi7021624
– ident: CIT0075
  doi: 10.1016/S1734-1140(09)70018-0
– ident: CIT0126
  doi: 10.1210/me.2006-0524
– ident: CIT0115
  doi: 10.18632/oncotarget.8730
– ident: CIT0152
  doi: 10.2741/3954
– ident: CIT0004
  doi: 10.1021/cr400698c
– ident: CIT0137
  doi: 10.1074/jbc.M402195200
– ident: CIT0122
  doi: 10.1124/pr.58.4.2
– ident: CIT0001
  doi: 10.1016/j.pbiomolbio.2015.05.002
– ident: CIT0019
  doi: 10.1016/j.chembiol.2010.06.010
– ident: CIT0113
  doi: 10.1038/nrc3239
– ident: CIT0129
  doi: 10.1530/jrf.0.0130101
– ident: CIT0032
  doi: 10.1002/anie.200801010
– ident: CIT0049
  doi: 10.1124/mol.114.093286
– ident: CIT0110
  doi: 10.1038/nrm2026
– ident: CIT0046
  doi: 10.1016/0014-2999(94)90442-1
– volume: 247
  start-page: 1211
  year: 1988
  ident: CIT0090
  publication-title: J Pharmacol Exp Ther
  doi: 10.1016/S0022-3565(25)13281-3
– ident: CIT0094
  doi: 10.1021/jm00383a010
– ident: CIT0016
  doi: 10.7164/antibiotics.46.741
– ident: CIT0063
  doi: 10.1021/ja030294z
– ident: CIT0128
  doi: 10.1073/pnas.241410198
– ident: CIT0107
  doi: 10.1038/417245a
– ident: CIT0084
  doi: 10.1074/jbc.R500017200
– ident: CIT0036
  doi: 10.1038/nrd3531
– ident: CIT0074
  doi: 10.1200/JCO.2007.14.9401
– ident: CIT0005
  doi: 10.1146/annurev-biophys-042910-155359
– ident: CIT0048
  doi: 10.1073/pnas.1220253110
– ident: CIT0095
  doi: 10.1128/AAC.30.1.110
– ident: CIT0042
  doi: 10.1126/science.274.5289.948
– ident: CIT0099
  doi: 10.1126/science.1261962
– ident: CIT0055
  doi: 10.1021/jm030347n
– ident: CIT0102
  doi: 10.1038/nrd2056
– ident: CIT0096
  doi: 10.1099/0022-1317-72-2-431
– ident: CIT0144
  doi: 10.1046/j.1365-313X.1997.12020441.x
– ident: CIT0059
  doi: 10.1073/pnas.1008255107
– ident: CIT0149
  doi: 10.1021/jm901062p
– ident: CIT0135
  doi: 10.1073/pnas.0407189102
– ident: CIT0009
  doi: 10.1007/978-1-61779-788-0_10
– ident: CIT0038
  doi: 10.1073/pnas.0805326105
– ident: CIT0057
  doi: 10.1002/anie.200351179
– ident: CIT0068
  doi: 10.1021/jm010257n
– ident: CIT0069
  doi: 10.1021/ja993309v
– ident: CIT0012
  doi: 10.1248/cpb.38.2960
– ident: CIT0130
  doi: 10.1677/joe.0.0750305
– ident: CIT0010
  doi: 10.1158/0008-5472.CAN-12-4501
– ident: CIT0027
  doi: 10.1529/biophysj.104.047753
– ident: CIT0050
  doi: 10.1146/annurev.biochem.75.101304.123901
– ident: CIT0061
  doi: 10.1016/S0968-0896(98)00130-8
– ident: CIT0120
  doi: 10.1038/nrd1551
– ident: CIT0035
  doi: 10.1016/S0022-2836(03)00306-1
– ident: CIT0071
  doi: 10.1073/pnas.1121005109
– ident: CIT0136
  doi: 10.1073/pnas.151244398
– ident: CIT0140
  doi: 10.1074/jbc.M111.308403
– ident: CIT0023
  doi: 10.1101/pdb.prot4947
– volume: 17
  start-page: 46
  year: 2010
  ident: CIT0037
  publication-title: Cell Chem Biol
– ident: CIT0022
  doi: 10.1002/jlac.19385330105
– ident: CIT0089
  doi: 10.1073/pnas.1107906108
– ident: CIT0085
  doi: 10.1016/j.bbrc.2004.07.096
– ident: CIT0092
  doi: 10.1126/science.1251915
– ident: CIT0098
  doi: 10.1126/science.3018924
– ident: CIT0124
  doi: 10.1038/nsmb.1855
SSID ssj0053833
Score 2.4914272
SecondaryResourceType review_article
Snippet Introduction: PPIs are involved in every disease and specific modulation of these PPIs with small molecules would significantly improve our prospects of...
PPIs are involved in every disease and specific modulation of these PPIs with small molecules would significantly improve our prospects of developing...
SourceID proquest
pubmed
crossref
informaworld
SourceType Aggregation Database
Index Database
Enrichment Source
Publisher
StartPage 925
SubjectTerms Biological Products - pharmacology
Chemical biology
Drug Design
Drug Discovery - methods
druggable genome
Humans
medicinal chemistry
Pharmaceutical Preparations - chemical synthesis
Pharmaceutical Preparations - chemistry
Pharmaceutical Preparations - metabolism
PPI stabilization
PPIs
Protein Binding
Protein Stability
Proteins - metabolism
Small Molecule Libraries
small molecules
tool compounds
X-ray crystallography
Title Stabilization of protein-protein interactions in drug discovery
URI https://www.tandfonline.com/doi/abs/10.1080/17460441.2017.1346608
https://www.ncbi.nlm.nih.gov/pubmed/28695752
https://www.proquest.com/docview/1917960559
Volume 12
WOSCitedRecordID wos000407431900005&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
journalDatabaseRights – providerCode: PRVAWR
  databaseName: Taylor & Francis Journals Complete
  customDbUrl:
  eissn: 1746-045X
  dateEnd: 99991231
  omitProxy: false
  ssIdentifier: ssj0053833
  issn: 1746-0441
  databaseCode: TFW
  dateStart: 20060601
  isFulltext: true
  titleUrlDefault: https://www.tandfonline.com
  providerName: Taylor & Francis
link http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV07T8MwELYQMLDwfpSXjISYSEkcJ3ZGhKg6INShEmWK7MRGSChFSYrUf8-dkxQYUAdYHHm4POyz77747jtCLn0dKCuU8sIs8gGgaOElmgnP11zZ2JgozN1MP4jHRzmZJKM2mrBqwyoRQ9uGKMLt1bi4la66iLgbcKJjH8w4BmaJfhDyOMZ03zUG0ATxl_887DZjWM6umjyKeCjTJfH8dpsf5ukHeenvLqgzRYOtf_iIbbLZ-qH0tlGcHbJiil1yNWqIrOfXdPyVl1Vd0ys6-qK4nu-Bi187Zt4mh5NOLXV8D6-F114p0lCUTdJEBR2al7MXiinAGDI63yfjwf34bui1pRi8jIuk9qQ0RgoG_gU3eDLJdBAzJYQ2CbOBCRUAjZxFUkeac2sV7CKgAjbPVWbB3oUHZLWYFuaIUJVnMhcmFgHT3DKrLNKAmZArZZlUSY_wbgLSrKUpx2oZb2nQspl2I5fiyKXtyPVIfyH23vB0LBNIvs9uWrsfJLapZpKGS2QvOlVIYTXiEYsqzHRWpYh-ARMCTOuRw0ZHFq_DZJyAc8yO__DkE7KBXRfkxk7Jal3OzBlZzz7q16o8d6oPrZhIaMeDp09p-QC4
linkProvider Taylor & Francis
linkToHtml http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV3dS8MwEA-igr74_TE_I8ieVl3TtGkfRRwT59hDQd9C0iYiSCdtJ-y_N5e2uj2MPehTKeX6kdzl7tL7_Q6h6650hWZCOF7id02CIpkTScKcrqRCB0r5XmpnesCGw_D1NZrFwkBZJeTQuiKKsGs1GDdsRjclcbcmig66xo9DZRa7cT0aBID3XfONrwX-_Lj30qzGxp5tO3kQcUCmQfEsus2cf5pjL10cg1pf1Nv-j6_YQVt1JIrvKtXZRSsq20PtUUVlPe3g-BeZVXRwG49-Sa6n-ybILy03b4XixGONLePDe-bURwxEFHkFmyjMCU7zyRsGEDAUjU4PUNx7iO_7Tt2MwUkoi0onDJUKGTERBlXwb5JINyCCMakiol3lCZNqpMQPpS8p1VqYdcQogU5TkWjj8bxDtJqNM3WMsEiTMGUqYC6RVBMtNBCBKY8KoUkoohaizQzwpCYqh34ZH9yt-UybkeMwcrweuRa6-RH7rJg6lglEs9PLS7tFoqt-JtxbInvV6AI39gg_WUSmxpOCQ_5rskKTqLXQUaUkP69DwiAy4TE5-cOTL9FGP34e8MHj8OkUbcIlW_JGztBqmU_UOVpPvsr3Ir-wdvANEw8C6A
linkToPdf http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV3dS8MwEA-iIr74_TE_I8ie1tmmWdM-ijoUx9jDwL2FpE1kIN1YO2H_vbm03dzD2IM-lVKuH8ld7nfN3e8QunelJzQTwvHjlmsCFMmcSBLmuJIKHSjV8hM70x3W7YaDQdQrswmzMq0SYmhdEEXYtRqMe5zoKiPuwYDowDVuHBKzWNPzaRBAue-Wgc4BKHm__VEtxsacbTd5EHFApiriWXWbJfe0RF66GoJaV9Te_4ePOEB7JQ7Fj4XiHKINlR6heq8gsp41cH9Rl5U1cB33FhTXs2MD8XPLzFvUcOKRxpbvYZg65REDDcWkKJrIzAlOJtNPDCXAkDI6O0H99kv_6dUpWzE4MWVR7oShUiEjBl9QBTuTRHoBEYxJFRHtKV-YQCMhrVC2JKVaC7OKGBXQSSJibfydf4o201GqzhEWSRwmTAXMI5JqooUGGjDlUyE0CUVUQ7SaAB6XNOXQLeOLeyWbaTVyHEaOlyNXQ8252Ljg6VgnEP2eXZ7bHyS66GbC_TWyd5UqcGONsMUiUjWaZhyiXxMTmjCths4KHZm_DgmDyIBjcvGHJ9-ind5zm3feuu-XaBeu2Hw3coU288lUXaPt-DsfZpMbawU__TgBmg
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Stabilization+of+protein-protein+interactions+in+drug+discovery&rft.jtitle=Expert+opinion+on+drug+discovery&rft.au=Andrei%2C+Sebastian+A.&rft.au=Sijbesma%2C+Eline&rft.au=Hann%2C+Michael&rft.au=Davis%2C+Jeremy&rft.date=2017-09-02&rft.pub=Taylor+%26+Francis&rft.issn=1746-0441&rft.eissn=1746-045X&rft.volume=12&rft.issue=9&rft.spage=925&rft.epage=940&rft_id=info:doi/10.1080%2F17460441.2017.1346608&rft.externalDBID=0YH&rft.externalDocID=1346608
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1746-0441&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1746-0441&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1746-0441&client=summon