Identification of novel 2-(1H-indol-1-yl)-benzohydrazides CXCR4 ligands impairing breast cancer growth and motility

Future Medicinal Chemistry
Fedora GrandeStefania Catalano

Abstract

Stromal-derived-factor-1 (SDF-1) and the G-protein-coupled receptor CXCR4 are involved in several physiological and pathological processes including breast cancer spread and progression. Several CXCR4 antagonists have currently reached advanced development stages as potential therapeutic agents for different diseases. A small series of novel CXCR4 ligands, based on a 2-(1H-indol-1-yl)-benzohydrazide scaffold, has been designed and synthesized. The interaction with CXCR4-active site was predicted by molecular docking and confirmed by whole cell-based [(125)I]-SDF-1 ligand competition binding assays. One of the synthesized compounds was particularly active in blocking SDF-1-induced breast cancer cell motility, proliferation and downstream signaling activation in different breast cancer cell models and coculture systems. The newly synthesized compounds represent suitable leads for the development of innovative therapeutic agents targeting CXCR4.

References

Mar 4, 1997·Proceedings of the National Academy of Sciences of the United States of America·C C BleulC R Mackay
Jul 5, 2003·Cancer Cell·Yibin KangJoan Massagué
Jan 9, 2004·Oncogene·Aaron Zefrin FernandisRamesh Kumar Ganju
Mar 18, 2004·Breast Cancer Research and Treatment·Bernd C SchmidRobert Zeillinger
Jul 21, 2004·Cancer Cell·Minna AllinenKornelia Polyak
Feb 13, 2007·Annual Review of Immunology·Samantha J AllenTracy M Handel
Mar 3, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·James R HarveySimi Ali
Feb 22, 2008·Current Pharmaceutical Design·Fedora GrandeNouri Neamati
Jun 10, 2008·Bioorganic & Medicinal Chemistry Letters·Satoshi UedaNobutaka Fujii
Dec 5, 2008·Journal of Medicinal Chemistry·Gebhard ThomaHans-Günter Zerwes
Apr 2, 2009·Expert Opinion on Investigational Drugs·Jan A Burger, David J Stewart
Jan 13, 2011·Experimental Cell Research·Dayanidhi RamanAnn Richmond
Aug 16, 2011·ACS Medicinal Chemistry Letters·Marilou LefrançoisEmanuel Escher
Oct 13, 2011·The Journal of Pathology·Frances R Balkwill
Apr 4, 2012·Viruses·Chukwuka A Didigu, Robert W Doms
Feb 6, 2013·Theranostics·Bikash DebnathNouri Neamati

❮ Previous
Next ❯

Methods Mentioned

BETA
competition binding
column chromatography
electrophoresis
PCR
biopsies

Software Mentioned

GraphPad Prism
Maestro
- Prism4
GLIDE
Protein Preparation Wizard tool
GraphPad

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Urologia Internationalis
Gerd Lümmen, Herbert Rübben
FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Kathryn E LukerGary D Luker
Theranostics
Bikash DebnathNouri Neamati
© 2021 Meta ULC. All rights reserved