2014
DOI: 10.1016/j.atherosclerosis.2014.06.008
|View full text |Cite
|
Sign up to set email alerts
|

A novel BET bromodomain inhibitor, RVX-208, shows reduction of atherosclerosis in hyperlipidemic ApoE deficient mice

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1
1

Citation Types

3
94
1

Year Published

2015
2015
2020
2020

Publication Types

Select...
7
1

Relationship

1
7

Authors

Journals

citations
Cited by 110 publications
(98 citation statements)
references
References 85 publications
3
94
1
Order By: Relevance
“…Most of the oral administration of HDL-raising agents, such as niacin, cholesteryl ester transfer protein (CETP) inhibitors, and fibrates, has yielded convincing results in increasing HDL-C levels, but the effects on reducing cardiovascular risk and enhancing RCT need to be further investigated (9)(10)(11). Turning on endogenous production of ApoA-I to facilitate new HDL particle formation is becoming one of the most attractive approaches, which is strongly supported by results from human ApoA-I transgenic mice and virus-mediated overexpression of ApoA-I in a mouse model of experimental atherosclerosis (11,12). RVX-208, a bromodomain and extraterminal domain inhibitor, is an orally active small molecule that upregulates ApoA-I production (12)(13)(14).…”
Section: Introductionmentioning
confidence: 92%
See 1 more Smart Citation
“…Most of the oral administration of HDL-raising agents, such as niacin, cholesteryl ester transfer protein (CETP) inhibitors, and fibrates, has yielded convincing results in increasing HDL-C levels, but the effects on reducing cardiovascular risk and enhancing RCT need to be further investigated (9)(10)(11). Turning on endogenous production of ApoA-I to facilitate new HDL particle formation is becoming one of the most attractive approaches, which is strongly supported by results from human ApoA-I transgenic mice and virus-mediated overexpression of ApoA-I in a mouse model of experimental atherosclerosis (11,12). RVX-208, a bromodomain and extraterminal domain inhibitor, is an orally active small molecule that upregulates ApoA-I production (12)(13)(14).…”
Section: Introductionmentioning
confidence: 92%
“…Turning on endogenous production of ApoA-I to facilitate new HDL particle formation is becoming one of the most attractive approaches, which is strongly supported by results from human ApoA-I transgenic mice and virus-mediated overexpression of ApoA-I in a mouse model of experimental atherosclerosis (11,12). RVX-208, a bromodomain and extraterminal domain inhibitor, is an orally active small molecule that upregulates ApoA-I production (12)(13)(14). However, in patients with CHD, administration of RVX-208 did not statistically reduce cardiovascular events and the percentage of coronary atheroma volume due to its small effect on HDL-C levels and significant side effects in the ASSURE study (15,16).…”
Section: Introductionmentioning
confidence: 98%
“…Whereas most BETis in development have similar affinity for both (i.e., pan) BET protein BDs, RVX-297 is a novel, orally bioavailable BETi with selectivity for BD2 (Kharenko et al, 2016). Apabetalone is another BD2-selective BETi currently in clinical trials for cardiovascular disease (McLure et al, 2013); the antiinflammatory properties of apabetalone have been demonstrated in a mouse model of atherosclerosis (Jahagirdar et al, 2014). To extend the understanding of the anti-inflammatory properties of RVX-297, we examined the activity of RVX-297 in vitro and in five preclinical in vivo models of autoimmune pathology including, the mouse LPS, rCIA, mCIA, mCAIA, and mouse EAE models.…”
Section: Discussionmentioning
confidence: 99%
“…RVX-297 was dosed orally for all animal studies and was prepared in formulation EA006 as described by Jahagirdar et al (2014). The concentration of the test compound in each preparation was verified by liquid chromatography tandem mass spectrometry.…”
Section: Compound Formulation In Animal Studiesmentioning
confidence: 99%
“…Interestingly, unlike other BET inhibitors, RVX-208 binds preferentially to the BD2 domain of BRD2 and BRD3 proteins. RVX-208 provides proof-of-concept that selective inhibition within the BET family is feasible [Picaud et al 2013;Jahagirdar et al 2014]. This observation may have clinical implications in cancer, for instance the development of BET inhibitors that spare BRDT and therefore may be more suitable for the paediatric population.…”
Section: The Development Of the Bet Proteins Inhibitorsmentioning
confidence: 99%