Design and synthesis of 1H-pyrazolo[3,4-b]pyridines targeting mitogen-activated protein kinase kinase 4 (MKK4) - A promising target for liver regeneration.


Journal

European journal of medicinal chemistry
ISSN: 1768-3254
Titre abrégé: Eur J Med Chem
Pays: France
ID NLM: 0420510

Informations de publication

Date de publication:
05 Jun 2021
Historique:
received: 22 10 2020
revised: 23 02 2021
accepted: 04 03 2021
pubmed: 2 4 2021
medline: 7 8 2021
entrez: 1 4 2021
Statut: ppublish

Résumé

Currently, the therapeutic options for treatment of liver failure are very limited. As mitogen-activated protein kinase kinase 4 (MKK4) has recently been identified by in vivo RNAi experiments to be a major regulator in hepatocyte regeneration, we pursued the development of a small molecule targeting this protein kinase. Starting from the approved BRAF

Identifiants

pubmed: 33794385
pii: S0223-5234(21)00220-8
doi: 10.1016/j.ejmech.2021.113371
pii:
doi:

Substances chimiques

1H-pyrazolo(3,4-b)pyridine 0
Protein Kinase Inhibitors 0
Pyrazoles 0
Pyridines 0
MAP Kinase Kinase 4 EC 2.7.12.2
MAP2K4 protein, human EC 2.7.12.2

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

113371

Informations de copyright

Copyright © 2021 Elsevier Masson SAS. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Bent Pfaffenrot (B)

Department of Pharmaceutical/Medicinal Chemistry an Tuebingen Center for Academic Drug Discovery (TüCAD(2)), Eberhard Karls Universität, Auf der Morgenstelle 8, 72076, Tübingen, DE, Germany.

Philip Klövekorn (P)

Department of Pharmaceutical/Medicinal Chemistry an Tuebingen Center for Academic Drug Discovery (TüCAD(2)), Eberhard Karls Universität, Auf der Morgenstelle 8, 72076, Tübingen, DE, Germany.

Michael Juchum (M)

Department of Pharmaceutical/Medicinal Chemistry an Tuebingen Center for Academic Drug Discovery (TüCAD(2)), Eberhard Karls Universität, Auf der Morgenstelle 8, 72076, Tübingen, DE, Germany.

Roland Selig (R)

HepaRegenix GmbH, Eisenbahnstraße 63, 72072, Tübingen, DE, Germany.

Wolfgang Albrecht (W)

HepaRegenix GmbH, Eisenbahnstraße 63, 72072, Tübingen, DE, Germany.

Lars Zender (L)

Department of Medical Oncology and Pneumology (Internal Medicine VIII), University Hospital Tuebingen, 72076, Tuebingen, DE, Germany; Cluster of Excellence 'Image Guided and Functionally Instructed Tumor Therapies' (iFIT), Eberhard Karls University of Tübingen, 72076, Tübingen, Germany; German Consortium for Translational Cancer Research (DKTK), Partner Site Tübingen, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.

Stefan A Laufer (SA)

Department of Pharmaceutical/Medicinal Chemistry an Tuebingen Center for Academic Drug Discovery (TüCAD(2)), Eberhard Karls Universität, Auf der Morgenstelle 8, 72076, Tübingen, DE, Germany; Cluster of Excellence 'Image Guided and Functionally Instructed Tumor Therapies' (iFIT), Eberhard Karls University of Tübingen, 72076, Tübingen, Germany; German Consortium for Translational Cancer Research (DKTK), Partner Site Tübingen, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany. Electronic address: stefan.laufer@uni-tuebingen.de.

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Classifications MeSH