Patterns of substrate affinity, competition, and degradation kinetics underlie biological activity of thalidomide analogs.

Hematologic Neoplasms / enzymology Humans Proteolysis / drug effects Substrate Specificity Thalidomide / analogs & derivatives Ubiquitin-Protein Ligases / chemistry

Journal

Blood
ISSN: 1528-0020
Titre abrégé: Blood
Pays: United States
ID NLM: 7603509

Informations de publication

Date de publication:
11 07 2019
Historique:
received: 19 11 2018
accepted: 26 04 2019
pubmed: 3 5 2019
medline: 4 1 2020
entrez: 3 5 2019
Statut: ppublish

Résumé

Pharmacologic agents that modulate ubiquitin ligase activity to induce protein degradation are a major new class of therapeutic agents, active in a number of hematologic malignancies. However, we currently have a limited understanding of the determinants of activity of these agents and how resistance develops. We developed and used a novel quantitative, targeted mass spectrometry (MS) assay to determine the relative activities, kinetics, and cell-type specificity of thalidomide and 4 analogs, all but 1 of which are in clinical use or clinical trials for hematologic malignancies. Thalidomide analogs bind the CRL4

Identifiants

DOI: 10.1182/blood.2019000789 PMID: 31043423 PMC: PMC6624968
pubmed: 31043423
pii: S0006-4971(20)42421-8
doi: 10.1182/blood.2019000789
pmc: PMC6624968
doi:

Substances chimiques

Thalidomide 4Z8R6ORS6L
Ubiquitin-Protein Ligases EC 2.3.2.27

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

160-170

Subventions

Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007753
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM038627
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA155258
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009216
Pays : United States
Organisme : NCI NIH HHS
ID : K12 CA087723
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007623
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL116324
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA066996
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2019 by The American Society of Hematology.

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Auteurs

Adam S Sperling (AS)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Division of Hematology, Brigham and Women's Hospital, Boston, MA.
Broad Institute of MIT and Harvard, Cambridge, MA.

Michael Burgess (M)

Broad Institute of MIT and Harvard, Cambridge, MA.

Hasmik Keshishian (H)

Broad Institute of MIT and Harvard, Cambridge, MA.

Jessica A Gasser (JA)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Division of Hematology, Brigham and Women's Hospital, Boston, MA.
Broad Institute of MIT and Harvard, Cambridge, MA.

Shruti Bhatt (S)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.

Max Jan (M)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Division of Hematology, Brigham and Women's Hospital, Boston, MA.
Broad Institute of MIT and Harvard, Cambridge, MA.

Mikołaj Słabicki (M)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Division of Hematology, Brigham and Women's Hospital, Boston, MA.
Broad Institute of MIT and Harvard, Cambridge, MA.
Division of Translational Oncology, National Center for Tumor Diseases Heidelberg, German Cancer Research Center, Heidelberg, Germany; and.

Rob S Sellar (RS)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Division of Hematology, Brigham and Women's Hospital, Boston, MA.
Broad Institute of MIT and Harvard, Cambridge, MA.
Department of Haematology, UCL Cancer Institute, University College London, London, United Kingdom.

Emma C Fink (EC)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Division of Hematology, Brigham and Women's Hospital, Boston, MA.
Broad Institute of MIT and Harvard, Cambridge, MA.
ORCID: 0000-0002-6589-8558

Peter G Miller (PG)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Division of Hematology, Brigham and Women's Hospital, Boston, MA.
Broad Institute of MIT and Harvard, Cambridge, MA.

Brian J Liddicoat (BJ)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Division of Hematology, Brigham and Women's Hospital, Boston, MA.
Broad Institute of MIT and Harvard, Cambridge, MA.
ORCID: 0000-0003-3644-2241

Quinlan L Sievers (QL)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Division of Hematology, Brigham and Women's Hospital, Boston, MA.
Broad Institute of MIT and Harvard, Cambridge, MA.
ORCID: 0000-0003-4875-0022

Rohan Sharma (R)

Division of Hematology, Brigham and Women's Hospital, Boston, MA.

Dylan N Adams (DN)

Division of Hematology, Brigham and Women's Hospital, Boston, MA.

Elyse A Olesinski (EA)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.

Mariateresa Fulciniti (M)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.

Namrata D Udeshi (ND)

Broad Institute of MIT and Harvard, Cambridge, MA.

Eric Kuhn (E)

Broad Institute of MIT and Harvard, Cambridge, MA.
ORCID: 0000-0001-6631-1950

Anthony Letai (A)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.

Nikhil C Munshi (NC)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.

Steven A Carr (SA)

Broad Institute of MIT and Harvard, Cambridge, MA.

Benjamin L Ebert (BL)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Division of Hematology, Brigham and Women's Hospital, Boston, MA.
Broad Institute of MIT and Harvard, Cambridge, MA.

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Classifications MeSH

questionsmedicales.fr › Hémopathies et maladies lymphatiques › Hémopathies › Tumeurs hématologiques › Patterns of substrate affinity, competition,...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Patterns of substrate affinity, competition,...
questionsmedicales.fr › Métabolisme › Protéolyse › Patterns of substrate affinity, competition,...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Spécificité du substrat › Patterns of substrate affinity, competition,...
questionsmedicales.fr › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Isoindoles › Phtalimides › Thalidomide › Patterns of substrate affinity, competition,...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Ligases › Ubiquitin-protein ligase complexes › Ubiquitin-protein ligases › Patterns of substrate affinity, competition,...