Apabetalone information

Apabetalone
Names
	IUPAC name 2-[4-(2-Hydroxyethoxy)-3,5-dimethylphenyl]-5,7-dimethoxy-4(3H)-quinazolinone
	Other names RVX208, RVX-208
Identifiers
CAS Number	1044870-39-4 ;
3D model (JSmol)	Interactive image;
ChEMBL	ChEMBL2393130;
ChemSpider	25069708;
DrugBank	DB12000;
ECHA InfoCard	100.242.963
EC Number	12-112-4;
KEGG	D11131;
PubChem CID	135564749;
UNII	8R4A7GDZ1D ;
CompTox Dashboard (EPA)	DTXSID90146502 ;
	InChI InChI=1S/C20H22N2O5/c1-11-7-13(8-12(2)18(11)27-6-5-23)19-21-15-9-14(25-3)10-16(26-4)17(15)20(24)22-19/h7-10,23H,5-6H2,1-4H3,(H,21,22,24) Key: NETXMUIMUZJUTB-UHFFFAOYSA-N;
	SMILES CC1=CC(=CC(=C1OCCO)C)C2=NC3=C(C(=CC(=C3)OC)OC)C(=O)N2;
Properties
Chemical formula	C20H22N2O5
Molar mass	370.405 g·mol−1
Density	1.3±0.1 g/cm3
Hazards
	GHS labelling:
Pictograms
Signal word	Warning
Hazard statements	H371
Precautionary statements	P260, P264, P270, P309+P311, P405, P501
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Apabetalone (development codes RVX 208, RVX-208, and RVX000222)^[1] is an orally available small molecule created by Resverlogix Corp.^[2] that is being evaluated in clinical trials for the treatment of atherosclerosis and associated cardiovascular disease (CVD).^[3]^[4] In the phase II clinical trial ASSURE in patients with angiographic coronary disease and low high-density lipoprotein cholesterol (HDL-C) levels, apabetalone showed no greater increase in HDL-cholesterol (HDL-c) and apolipoprotein A-I (ApoA-I) levels or incremental regression of atherosclerosis than administration of placebo, while causing a statistically significant greater incidence of elevated liver enzymes.^[5] However, pooled analysis of the effect of apabetalone in three phase II clinical trials ASSERT, ASSURE, and SUSTAIN demonstrated increases in HDL-cholesterol (HDL-c) and apolipoprotein A-I (ApoA-I) levels, as well as decreases in the incidence of major adverse cardiac events (MACE).^[6] Reduction of MACE was more profound in patients with diabetes mellitus. In a short-term study in prediabetics, favorable changes in glucose metabolism were observed in patients receiving apabetalone.^[7] An international, multicenter phase III trial, “Effect of RVX000222 on Time to Major Adverse Cardiovascular Events in High-Risk Type 2 Diabetes Mellitus Subjects with Coronary Artery Disease” (BETonMACE) commenced in October 2015.^[8] The trial is designed to determine whether apabetalone in combination with statins can decrease cardiac events compared to treatment with statins alone.

^ E. McNeill, RVX-208, a stimulator of apolipoprotein AI gene expression for the treatment of cardiovascular diseases, Current opinion in investigational drugs, 11 (2010) 357-364.
^ "Home - Resverlogix Corp".
^ Nicholls, Stephen J.; Gordon, Allan; Johannson, Jan; Ballantyne, Christie M.; Barter, Philip J.; Brewer, H. Bryan; Kastelein, John J. P.; Wong, Norman C.; Borgman, Marilyn R. N.; Nissen, Steven E. (17 February 2012). "ApoA-I Induction as a Potential Cardioprotective Strategy: Rationale for the SUSTAIN and ASSURE Studies". Cardiovascular Drugs and Therapy. 26 (2): 181–187. doi:10.1007/s10557-012-6373-5. PMID 22349989. S2CID 24927630.
^ Nicholls, Stephen J.; Gordon, Allan; Johansson, Jan; Wolski, Kathy; Ballantyne, Christie M.; Kastelein, John J.P.; Taylor, Allen; Borgman, Marilyn; Nissen, Steven E. (March 2011). "Efficacy and Safety of a Novel Oral Inducer of Apolipoprotein A-I Synthesis in Statin-Treated Patients With Stable Coronary Artery Disease". Journal of the American College of Cardiology. 57 (9): 1111–1119. doi:10.1016/j.jacc.2010.11.015. PMID 21255957.
^ S.J. Nicholls, R. Puri, K. Wolski, C.M. Ballantyne, P.J. Barter, H.B. Brewer, J.J.P. Kastelein, B. Hu, K. Uno, Y. Kataoka, J-P. R. Herrman, B. Merkely, M. Borgman, S.E. Nissen. Effect of the BET Protein Inhibitor, RVX-208, on Progression of Coronary Atherosclerosis: Results of the Phase 2b, Randomized, Double-Blind, Multicenter, ASSURE Trial, Am J Cardioovascular Drugs, 16 (2016) 55-65.
^ J. Johansson, A. Gordon, C. Halliday, N.C. Wong, Effects of RVX-208 on major adverse cardiac events (MACE), apolipoprotein A-I and High-Density-Lipoproteins; A post-hoc analysis from the pooled SUSTAIN and ASSURE clinical trials (Congress abstract), Eur Heart J Suppl, 35 (2014) 723-724.
^ Siebel, Andrew L.; Trinh, Si Khiang; Formosa, Melissa F.; Mundra, Piyushkumar A.; Natoli, Alaina K.; Reddy-luthmoodoo, Medini; Huynh, Kevin; Khan, Anmar A.; Carey, Andrew L. (2016-06-01). "Effects of the BET-inhibitor, RVX-208 on the HDL lipidome and glucose metabolism in individuals with prediabetes: A randomize,ref.ed controlled trial". Metabolism. 65 (6): 904–914. doi:10.1016/j.metabol.2016.03.002. ISSN 0026-0495. PMID 27173469.
^ "www.clinicaltrials.gov". 20 August 2020.

[1] E. McNeill, RVX-208, a stimulator of apolipoprotein AI gene expression for the treatment of cardiovascular diseases, Current opinion in investigational drugs, 11 (2010) 357-364.

[2] "Home - Resverlogix Corp".

[3] Nicholls, Stephen J.; Gordon, Allan; Johannson, Jan; Ballantyne, Christie M.; Barter, Philip J.; Brewer, H. Bryan; Kastelein, John J. P.; Wong, Norman C.; Borgman, Marilyn R. N.; Nissen, Steven E. (17 February 2012). "ApoA-I Induction as a Potential Cardioprotective Strategy: Rationale for the SUSTAIN and ASSURE Studies". Cardiovascular Drugs and Therapy. 26 (2): 181–187. doi:10.1007/s10557-012-6373-5. PMID 22349989. S2CID 24927630.

[4] Nicholls, Stephen J.; Gordon, Allan; Johansson, Jan; Wolski, Kathy; Ballantyne, Christie M.; Kastelein, John J.P.; Taylor, Allen; Borgman, Marilyn; Nissen, Steven E. (March 2011). "Efficacy and Safety of a Novel Oral Inducer of Apolipoprotein A-I Synthesis in Statin-Treated Patients With Stable Coronary Artery Disease". Journal of the American College of Cardiology. 57 (9): 1111–1119. doi:10.1016/j.jacc.2010.11.015. PMID 21255957.

[5] S.J. Nicholls, R. Puri, K. Wolski, C.M. Ballantyne, P.J. Barter, H.B. Brewer, J.J.P. Kastelein, B. Hu, K. Uno, Y. Kataoka, J-P. R. Herrman, B. Merkely, M. Borgman, S.E. Nissen. Effect of the BET Protein Inhibitor, RVX-208, on Progression of Coronary Atherosclerosis: Results of the Phase 2b, Randomized, Double-Blind, Multicenter, ASSURE Trial, Am J Cardioovascular Drugs, 16 (2016) 55-65.

[6] J. Johansson, A. Gordon, C. Halliday, N.C. Wong, Effects of RVX-208 on major adverse cardiac events (MACE), apolipoprotein A-I and High-Density-Lipoproteins; A post-hoc analysis from the pooled SUSTAIN and ASSURE clinical trials (Congress abstract), Eur Heart J Suppl, 35 (2014) 723-724.

[7] Siebel, Andrew L.; Trinh, Si Khiang; Formosa, Melissa F.; Mundra, Piyushkumar A.; Natoli, Alaina K.; Reddy-luthmoodoo, Medini; Huynh, Kevin; Khan, Anmar A.; Carey, Andrew L. (2016-06-01). "Effects of the BET-inhibitor, RVX-208 on the HDL lipidome and glucose metabolism in individuals with prediabetes: A randomize,ref.ed controlled trial". Metabolism. 65 (6): 904–914. doi:10.1016/j.metabol.2016.03.002. ISSN 0026-0495. PMID 27173469.

[8] "www.clinicaltrials.gov". 20 August 2020.

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