Identification of 2,4-diamino-6,7-dimethoxyquinoline derivatives as G9a inhibitors†Electronic supplementary information (ESI) available. See DOI: 10.1039/c4md00274a

MedChemComm
Nitipol SrimongkolpithakMatthew J Fuchter

Abstract

G9a is a histone lysine methyltransferase (HKMT) involved in epigenetic regulation via the installation of histone methylation marks. 6,7-Dimethoxyquinazoline analogues, such as BIX-01294, are established as potent, substrate competitive inhibitors of G9a. With an objective to identify novel chemotypes for substrate competitive inhibitors of G9a, we have designed and synthesised a range of heterocyclic scaffolds, and investigated their ability to inhibit G9a. These studies have led to improved understanding of the key pharmacophoric features of BIX-01294 and the identification of a new core quinoline inhibitory scaffold, which retains excellent potency and high selectivity. Molecular docking was carried out to explain the observed in vitro data.

References

Feb 10, 2007·Molecular Cell·Stefan KubicekThomas Jenuwein
Apr 29, 2008·Nature Chemical Biology·Philipp RathertAlbert Jeltsch
Feb 17, 2009·Nature Structural & Molecular Biology·Yanqi ChangXiaodong Cheng
May 4, 2010·Journal of Molecular Biology·Yanqi ChangXiaodong Cheng
Jul 7, 2010·Molecular Cell·Jason S LeeSung Hee Baek
Jun 24, 2011·PloS One·Hongtao Zhao, Danzhi Huang
Jul 12, 2011·Nature Chemical Biology·Masoud VedadiJian Jin
Jul 26, 2011·Journal of Medicinal Chemistry·Feng LiuJian Jin
Jan 10, 2012·Journal of Molecular Biology·Anup K UpadhyayXiaodong Cheng
Sep 27, 2012·Proceedings of the National Academy of Sciences of the United States of America·Nicholas A MalmquistMatthew J Fuchter
Feb 16, 2013·Journal of Chemical Information and Modeling·Kong T NguyenMatthieu Schapira
Oct 10, 2013·Journal of Medicinal Chemistry·Feng LiuJian Jin
Feb 11, 2014·Nature Medicine·Laurent DembéléDominique Mazier
Jun 6, 2014·ACS Medicinal Chemistry Letters·Ramzi F SweisWilliam N Pappano

❮ Previous
Next ❯

Citations

Aug 11, 2015·Frontiers in Chemistry·Chunngai Hui, Tao Ye
Aug 23, 2016·Future Medicinal Chemistry·Uttara Soumyanarayanan, Brian W Dymock
Apr 20, 2017·Journal of Medicinal Chemistry·Andrew C FlickChristopher J O'Donnell
Oct 10, 2015·Journal of Laboratory Automation·Bonnie EdwardsCarl Peters
May 30, 2019·Future Medicinal Chemistry·Mariasoosai Ramya Chandar CharlesMohane Selvaraj Coumar
May 11, 2019·Chemistry : a European Journal·Shingo HirashimaHiroshi Sugiyama
Jul 1, 2017·Bioorganic & Medicinal Chemistry·Yan XiongJian Jin
May 31, 2021·European Journal of Medicinal Chemistry·Antonino LauriaAnnamaria Martorana

❮ Previous
Next ❯

Methods Mentioned

BETA
X-ray

Software Mentioned

Glide
RDkit
Epik

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.