NDLI: RVX-208, an Inducer of ApoA-I in Humans, Is a BET Bromodomain Antagonist

Content Provider	PubMed Central
Author	Mclure, Kevin G. Gesner, Emily M. Laura, Tsujikawa Kharenko, Olesya A. Attwell, Sarah Campeau, Eric Wasiak, Sylwia Stein, Adam White, Andre Fontano, Eric Suto, Robert K. Wong, Norman C. W. Wagner, Gregory S. Hansen, Henrik C. Young, Peter R.
Editor	Vertessy, Beata G.
Copyright Year	2013
Abstract	Increased synthesis of Apolipoprotein A-I (ApoA-I) and HDL is believed to provide a new approach to treating atherosclerosis through the stimulation of reverse cholesterol transport. RVX-208 increases the production of ApoA-I in hepatocytes in vitro, and in vivo in monkeys and humans, which results in increased HDL-C, but the molecular target was not previously reported. Using binding assays and X-ray crystallography, we now show that RVX-208 selectively binds to bromodomains of the BET (Bromodomain and Extra Terminal) family, competing for a site bound by the endogenous ligand, acetylated lysine, and that this accounts for its pharmacological activity. siRNA experiments further suggest that induction of ApoA-I mRNA is mediated by BET family member BRD4. These data indicate that RVX-208 increases ApoA-I production through an epigenetic mechanism and suggests that BET inhibition may be a promising new approach to the treatment of atherosclerosis.
Related Links	http://dx.doi.org/10.1371/journal.pone.0083190
Starting Page	83190
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	12
Volume Number	8
Language	English
Publisher	Public Library of Science
Publisher Date	2013-12-31
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

RVX-208, an inhibitor of BET transcriptional regulators with selectivity for the second bromodomain

SP071APABETALONE (RVX-208), A SELECTIVE BROMODOMAIN AND EXTRA-TERMINAL (BET) PROTEIN INHIBITOR, DECREASES ABUNDANCE AND ACTIVITY OF COMPLEMENT PROTEINS IN VITRO, IN MICE AND IN CLINICAL STUDIES

RVX-208, an inhibitor of BET transcriptional regulators with selectivity for the second bromodomain.

BET inhibitors RVX-208 and PFI-1 reactivate HIV-1 from latency

Bromodomain and Extraterminal Protein Inhibitor, Apabetalone (RVX-208), Reduces ACE2 Expression and Attenuates SARS-Cov-2 Infection In Vitro

Selective inhibition mechanism of RVX-208 to the second bromodomain of bromo and extraterminal proteins: insight from microsecond molecular dynamics simulations

Downregulation of the Complement Cascade In Vitro, in Mice and in Patients with Cardiovascular Disease by the BET Protein Inhibitor Apabetalone (RVX-208)

Apabetalone (RVX-208) reduces vascular inflammation in vitro and in CVD patients by a BET-dependent epigenetic mechanism

BET protein inhibitor apabetalone (RVX-208) suppresses pro-inflammatory hyper-activation of monocytes from patients with cardiovascular disease and type 2 diabetes

RVX-208, an Inducer of ApoA-I in Humans, Is a BET Bromodomain Antagonist

Similar Documents

RVX-208, an inhibitor of BET transcriptional regulators with selectivity for the second bromodomain

SP071APABETALONE (RVX-208), A SELECTIVE BROMODOMAIN AND EXTRA-TERMINAL (BET) PROTEIN INHIBITOR, DECREASES ABUNDANCE AND ACTIVITY OF COMPLEMENT PROTEINS IN VITRO, IN MICE AND IN CLINICAL STUDIES

RVX-208, an inhibitor of BET transcriptional regulators with selectivity for the second bromodomain.

BET inhibitors RVX-208 and PFI-1 reactivate HIV-1 from latency

Bromodomain and Extraterminal Protein Inhibitor, Apabetalone (RVX-208), Reduces ACE2 Expression and Attenuates SARS-Cov-2 Infection In Vitro

Selective inhibition mechanism of RVX-208 to the second bromodomain of bromo and extraterminal proteins: insight from microsecond molecular dynamics simulations

Downregulation of the Complement Cascade In Vitro, in Mice and in Patients with Cardiovascular Disease by the BET Protein Inhibitor Apabetalone (RVX-208)

Apabetalone (RVX-208) reduces vascular inflammation in vitro and in CVD patients by a BET-dependent epigenetic mechanism

BET protein inhibitor apabetalone (RVX-208) suppresses pro-inflammatory hyper-activation of monocytes from patients with cardiovascular disease and type 2 diabetes

RVX-208, an Inducer of ApoA-I in Humans, Is a BET Bromodomain Antagonist