Design, synthesis, and biological characterization of a new class of symmetrical polyamine-based small molecule CXCR4 antagonists.


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:
15 Aug 2020
Historique:
received: 21 02 2020
revised: 14 04 2020
accepted: 27 04 2020
pubmed: 4 6 2020
medline: 24 10 2020
entrez: 4 6 2020
Statut: ppublish

Résumé

CXCR4, a well-studied coreceptor of human immunodeficiency virus type 1 (HIV-1) entry, recognizes its cognate ligand SDF-1α (also named CXCL12) which plays many important roles, including regulating immune cells, controlling hematopoietic stem cells, and directing cancer cells migration. These pleiotropic roles make CXCR4 an attractive target to mitigate human disorders. Here a new class of symmetrical polyamines was designed and synthesized as potential small molecule CXCR4 antagonists. Among them, a representative compound 21 (namely HF50731) showed strong CXCR4 binding affinity (mean IC

Identifiants

pubmed: 32492596
pii: S0223-5234(20)30381-0
doi: 10.1016/j.ejmech.2020.112410
pii:
doi:

Substances chimiques

CXCL12 protein, human 0
CXCR4 protein, human 0
Chemokine CXCL12 0
Peptide Fragments 0
Polyamines 0
Receptors, CXCR4 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

112410

Informations de copyright

Copyright © 2020 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

Xiong Fang (X)

Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, 100084, China.

Qian Meng (Q)

Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, 100084, China.

Huijun Zhang (H)

Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, 100084, China.

Boqiang Liang (B)

Nobel Institute of Biomedicine, Zhuhai, 519080, China.

Siyu Zhu (S)

Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, 100084, China.

Juan Wang (J)

Nobel Institute of Biomedicine, Zhuhai, 519080, China.

Chaozai Zhang (C)

Department of Medicine, University of California at San Diego, La Jolla, CA, 92037, USA.

Lina S Huang (LS)

Department of Medicine, University of California at San Diego, La Jolla, CA, 92037, USA.

Xingquan Zhang (X)

Department of Medicine, University of California at San Diego, La Jolla, CA, 92037, USA.

Robert T Schooley (RT)

Department of Medicine, University of California at San Diego, La Jolla, CA, 92037, USA.

Jing An (J)

Department of Medicine, University of California at San Diego, La Jolla, CA, 92037, USA.

Yan Xu (Y)

Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, 100084, China; School of Life and Health Sciences, Chinese University of Hong Kong, Shenzhen, China. Electronic address: yanxu@cuhk.edu.cn.

Ziwei Huang (Z)

Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, 100084, China. Electronic address: zwhny@yahoo.com.

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Classifications MeSH