Apabetalone | RVX-208 | CAS#1044870-39-4 | BET inhibitor

MedKoo Cat#: 206118 | Name: Apabetalone

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Apabetalone, also known as RVX-208, is a potent inhibitor of BET bromodomains. RVX-208 functions by removing atherosclerotic plaque via reverse cholesterol transport (RCT). 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. RVX-208 may be a promising new approach to the treatment of atherosclerosis.

Chemical Structure

Apabetalone

CAS#1044870-39-4

Theoretical Analysis

MedKoo Cat#: 206118

Name: Apabetalone

CAS#: 1044870-39-4

Chemical Formula: C20H22N2O5

Exact Mass: 370.1529

Molecular Weight: 370.40

Elemental Analysis: C, 64.85; H, 5.99; N, 7.56; O, 21.60

Price and Availability

Size	Price	Availability
50mg	USD 150.00	Ready to ship
100mg	USD 250.00	Ready to ship
200mg	USD 450.00	Ready to ship
500mg	USD 950.00	Ready to ship
1g	USD 1,650.00	Ready to ship
2g	USD 2,950.00	Ready to ship
5g	USD 6,550.00	Ready to ship

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Related CAS #

No Data

Synonym

RVX208; RVX 208; RVX-208; Apabetalone.

IUPAC/Chemical Name

2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one

InChi Key

NETXMUIMUZJUTB-UHFFFAOYSA-N

InChi Code

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)

SMILES Code

O=C1NC(C2=CC(C)=C(OCCO)C(C)=C2)=NC3=C1C(OC)=CC(OC)=C3

Appearance

white solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A8T04K16

QC Data

View QC data: current batch, Lot#A8T04K16

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Apabetalone (RVX-208, RVX-000222) is a potent BET bromodomain inhibitor with IC50 of 0.510 μM for BD2 in a cell-free assay, about 170-fold selectivity over BD1.

In vitro activity:

Apabetalone (RVX-208) competes with binding of an acetylated histone peptide to tandem BD1 BD2 protein constructs of the four BET proteins, with IC50s between 0.5 and 1.8 µM. Apabetalone increases the production of ApoA-I in hepatocytes in vitro, which results in increased high density lipoprotein cholesterol (HDL-C). Apabetalone 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. Apabetalone increases Apolipoprotein A-I (ApoA-I) production through an epigenetic mechanism and suggests that BET inhibition may be a promising new approach to the treatment of atherosclerosis. Apabetalone increases ApoA-I expression in liver cells. Reference: PLoS One. 2013 Dec 31;8(12):e83190. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24391744/

In vivo activity:

In the atherosclerosis prophylactic treatment study design, mice are fed a Western diet concurrent with the treatment with 150 mg/kg/dose b.i.d. for 12 weeks. Mice are sacrificed at 12 weeks after treatment. There is a progressive increase in body weight in both the vehicle treated as well as the Apabetalone (RVX-208) treated groups. However, there is only an increase of 4 g (from 24 g to 28 g) body weight after 12 weeks on Western diet in the Apabetalone treated group whereas this increase is found to be 9 g (25 g-34 g) in the vehicle treated group. The significant decrease in body weight gain in Apabetalone treated mice is not due to decreased feed consumption, suggesting a positive attribute of the molecule. Plasma lipid measurements are done at 6 weeks and 12 weeks of treatment with either the vehicle or Apabetalone. Compared to the vehicle control animals, Apabetalone treated mice show significant increase (~200%) in the levels of HDL-C at 6 weeks of treatment, which is sustained until end of the study (12 weeks). Reference: Atherosclerosis. 2014 Sep;236(1):91-100. https://linkinghub.elsevier.com/retrieve/pii/S0021-9150(14)01238-6

	Solvent	mg/mL	mM
Solubility
	DMSO	74.0	199.78

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 370.40 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

In vitro protocol:

1. McLure KG, Gesner EM, Tsujikawa L, Kharenko OA, Attwell S, Campeau E, Wasiak S, Stein A, White A, Fontano E, Suto RK, Wong NC, Wagner GS, Hansen HC, Young PR. RVX-208, an inducer of ApoA-I in humans, is a BET bromodomain antagonist. PLoS One. 2013 Dec 31;8(12):e83190. doi: 10.1371/journal.pone.0083190. PMID: 24391744; PMCID: PMC3877016. 2. Bailey D, Jahagirdar R, Gordon A, Hafiane A, Campbell S, Chatur S, Wagner GS, Hansen HC, Chiacchia FS, Johansson J, Krimbou L, Wong NC, Genest J. RVX-208: a small molecule that increases apolipoprotein A-I and high-density lipoprotein cholesterol in vitro and in vivo. J Am Coll Cardiol. 2010 Jun 8;55(23):2580-9. doi: 10.1016/j.jacc.2010.02.035. Erratum in: J Am Coll Cardiol. 2010 Aug 31;56(10):825. PMID: 20513599.

In vivo protocol:

1. Jahagirdar R, Zhang H, Azhar S, Tobin J, Attwell S, Yu R, Wu J, McLure KG, Hansen HC, Wagner GS, Young PR, Srivastava RA, Wong NC, Johansson J. A novel BET bromodomain inhibitor, RVX-208, shows reduction of atherosclerosis in hyperlipidemic ApoE deficient mice. Atherosclerosis. 2014 Sep;236(1):91-100. doi: 10.1016/j.atherosclerosis.2014.06.008. Epub 2014 Jun 28. PMID: 25016363. 2. Bailey D, Jahagirdar R, Gordon A, Hafiane A, Campbell S, Chatur S, Wagner GS, Hansen HC, Chiacchia FS, Johansson J, Krimbou L, Wong NC, Genest J. RVX-208: a small molecule that increases apolipoprotein A-I and high-density lipoprotein cholesterol in vitro and in vivo. J Am Coll Cardiol. 2010 Jun 8;55(23):2580-9. doi: 10.1016/j.jacc.2010.02.035. Erratum in: J Am Coll Cardiol. 2010 Aug 31;56(10):825. PMID: 20513599.

1: Allison S. Apabetalone in chronic kidney disease. Nat Rev Nephrol. 2021 Jul;17(7):437. doi: 10.1038/s41581-021-00443-1. PMID: 33990792. 2: Mohammed SA, Albiero M, Ambrosini S, Gorica E, Karsai G, Caravaggi CM, Masi S, Camici GG, Wenzl FA, Calderone V, Madeddu P, Sciarretta S, Matter CM, Spinetti G, Lüscher TF, Ruschitzka F, Costantino S, Fadini GP, Paneni F. The BET Protein Inhibitor Apabetalone Rescues Diabetes-Induced Impairment of Angiogenic Response by Epigenetic Regulation of Thrombospondin-1. Antioxid Redox Signal. 2022 Apr;36(10-12):667-684. doi: 10.1089/ars.2021.0127. Epub 2022 Apr 1. PMID: 34913726. 3: Gilham D, Tsujikawa LM, Sarsons CD, Halliday C, Wasiak S, Stotz SC, Jahagirdar R, Sweeney M, Johansson JO, Wong NCW, Kalantar-Zadeh K, Kulikowski E. Apabetalone downregulates factors and pathways associated with vascular calcification. Atherosclerosis. 2019 Jan;280:75-84. doi: 10.1016/j.atherosclerosis.2018.11.002. Epub 2018 Nov 14. PMID: 30476723. 4: Brandts J, Ray KK. Apabetalone - BET protein inhibition in cardiovascular disease and Type 2 diabetes. Future Cardiol. 2020 Sep;16(5):385-395. doi: 10.2217/fca-2020-0017. Epub 2020 May 7. PMID: 32378426. 5: Nicholls SJ, Schwartz GG, Buhr KA, Ginsberg HN, Johansson JO, Kalantar-Zadeh K, Kulikowski E, Toth PP, Wong N, Sweeney M, Ray KK; BETonMACE Investigators. Apabetalone and hospitalization for heart failure in patients following an acute coronary syndrome: a prespecified analysis of the BETonMACE study. Cardiovasc Diabetol. 2021 Jan 7;20(1):13. doi: 10.1186/s12933-020-01199-x. PMID: 33413345; PMCID: PMC7791841. 6: Tsujikawa LM, Fu L, Das S, Halliday C, Rakai BD, Stotz SC, Sarsons CD, Gilham D, Daze E, Wasiak S, Studer D, Rinker KD, Sweeney M, Johansson JO, Wong NCW, Kulikowski E. Apabetalone (RVX-208) reduces vascular inflammation in vitro and in CVD patients by a BET-dependent epigenetic mechanism. Clin Epigenetics. 2019 Jul 12;11(1):102. doi: 10.1186/s13148-019-0696-z. PMID: 31300040; PMCID: PMC6626370. 7: Chelladurai P, Boucherat O, Stenmark K, Kracht M, Seeger W, Bauer UM, Bonnet S, Pullamsetti SS. Targeting histone acetylation in pulmonary hypertension and right ventricular hypertrophy. Br J Pharmacol. 2021 Jan;178(1):54-71. doi: 10.1111/bph.14932. Epub 2020 Jan 26. PMID: 31749139. 8: Haarhaus M, Ray KK, Nicholls SJ, Schwartz GG, Kulikowski E, Johansson JO, Sweeney M, Halliday C, Lebioda K, Wong N, Brandenburg V, Beddhu S, Tonelli M, Zoccali C, Kalantar-Zadeh K. Apabetalone lowers serum alkaline phosphatase and improves cardiovascular risk in patients with cardiovascular disease. Atherosclerosis. 2019 Nov;290:59-65. doi: 10.1016/j.atherosclerosis.2019.09.002. Epub 2019 Sep 17. PMID: 31568963. 9: Wasiak S, Tsujikawa LM, Halliday C, Stotz SC, Gilham D, Jahagirdar R, Kalantar-Zadeh K, Robson R, Sweeney M, Johansson JO, Wong NC, Kulikowski E. Benefit of Apabetalone on Plasma Proteins in Renal Disease. Kidney Int Rep. 2017 Dec 8;3(3):711-721. doi: 10.1016/j.ekir.2017.12.001. PMID: 29854980; PMCID: PMC5976837. 10: Wasiak S, Dzobo KE, Rakai BD, Kaiser Y, Versloot M, Bahjat M, Stotz SC, Fu L, Sweeney M, Johansson JO, Wong NCW, Stroes ESG, Kroon J, Kulikowski E. BET protein inhibitor apabetalone (RVX-208) suppresses pro-inflammatory hyper- activation of monocytes from patients with cardiovascular disease and type 2 diabetes. Clin Epigenetics. 2020 Nov 11;12(1):166. doi: 10.1186/s13148-020-00943-0. PMID: 33172487; PMCID: PMC7657365. 11: Kalantar-Zadeh K, Schwartz GG, Nicholls SJ, Buhr KA, Ginsberg HN, Johansson JO, Kulikowski E, Lebioda K, Toth PP, Wong N, Sweeney M, Ray KK; BETonMACE Investigators. Effect of Apabetalone on Cardiovascular Events in Diabetes, CKD, and Recent Acute Coronary Syndrome: Results from the BETonMACE Randomized Controlled Trial. Clin J Am Soc Nephrol. 2021 May 8;16(5):705-716. doi: 10.2215/CJN.16751020. Epub 2021 Apr 27. PMID: 33906908; PMCID: PMC8259488. 12: Ray KK, Nicholls SJ, Buhr KA, Ginsberg HN, Johansson JO, Kalantar-Zadeh K, Kulikowski E, Toth PP, Wong N, Sweeney M, Schwartz GG; BETonMACE Investigators and Committees. Effect of Apabetalone Added to Standard Therapy on Major Adverse Cardiovascular Events in Patients With Recent Acute Coronary Syndrome and Type 2 Diabetes: A Randomized Clinical Trial. JAMA. 2020 Apr 28;323(16):1565-1573. doi: 10.1001/jama.2020.3308. PMID: 32219359; PMCID: PMC7101505. 13: Wasiak S, Gilham D, Daze E, Tsujikawa LM, Halliday C, Stotz SC, Rakai BD, Fu L, Jahagirdar R, Sweeney M, Johansson JO, Wong NCW, Kulikowski E. Epigenetic Modulation by Apabetalone Counters Cytokine-Driven Acute Phase Response In Vitro, in Mice and in Patients with Cardiovascular Disease. Cardiovasc Ther. 2020 Jul 21;2020:9397109. doi: 10.1155/2020/9397109. PMID: 32821285; PMCID: PMC7416228. 14: Mills RJ, Humphrey SJ, Fortuna PRJ, Lor M, Foster SR, Quaife-Ryan GA, Johnston RL, Dumenil T, Bishop C, Rudraraju R, Rawle DJ, Le T, Zhao W, Lee L, Mackenzie-Kludas C, Mehdiabadi NR, Halliday C, Gilham D, Fu L, Nicholls SJ, Johansson J, Sweeney M, Wong NCW, Kulikowski E, Sokolowski KA, Tse BWC, Devilée L, Voges HK, Reynolds LT, Krumeich S, Mathieson E, Abu-Bonsrah D, Karavendzas K, Griffen B, Titmarsh D, Elliott DA, McMahon J, Suhrbier A, Subbarao K, Porrello ER, Smyth MJ, Engwerda CR, MacDonald KPA, Bald T, James DE, Hudson JE. BET inhibition blocks inflammation-induced cardiac dysfunction and SARS-CoV-2 infection. Cell. 2021 Apr 15;184(8):2167-2182.e22. doi: 10.1016/j.cell.2021.03.026. Epub 2021 Mar 16. PMID: 33811809; PMCID: PMC7962543. 15: Borck PC, Guo LW, Plutzky J. BET Epigenetic Reader Proteins in Cardiovascular Transcriptional Programs. Circ Res. 2020 Apr 24;126(9):1190-1208. doi: 10.1161/CIRCRESAHA.120.315929. Epub 2020 Apr 23. PMID: 32324495; PMCID: PMC8111334. 16: Kulikowski E, Halliday C, Johansson J, Sweeney M, Lebioda K, Wong N, Haarhaus M, Brandenburg V, Beddhu S, Tonelli M, Zoccali C, Kalantar-Zadeh K. Apabetalone Mediated Epigenetic Modulation is Associated with Favorable Kidney Function and Alkaline Phosphatase Profile in Patients with Chronic Kidney Disease. Kidney Blood Press Res. 2018;43(2):449-457. doi: 10.1159/000488257. Epub 2018 Mar 16. PMID: 29566379. 17: Fu L, Wasiak S, Tsujikawa LM, Rakai BD, Stotz SC, Wong NCW, Johansson JO, Sweeney M, Mohan CM, Khan A, Kulikowski E. Inhibition of epigenetic reader proteins by apabetalone counters inflammation in activated innate immune cells from Fabry disease patients receiving enzyme replacement therapy. Pharmacol Res Perspect. 2022 Jun;10(3):e00949. doi: 10.1002/prp2.949. PMID: 35417091; PMCID: PMC9007222. 18: Zhang XX, Lin J, Liang TZ, Duan H, Tan XH, Xi BM, Li L, Liu SW. The BET bromodomain inhibitor apabetalone induces apoptosis of latent HIV-1 reservoir cells following viral reactivation. Acta Pharmacol Sin. 2019 Jan;40(1):98-110. doi: 10.1038/s41401-018-0027-5. Epub 2018 May 22. PMID: 29789664; PMCID: PMC6318340. 19: Shahid S, Pantakani M, Binder L, Fischer A, Pantakani K, Asif AR. Small Molecule BRD4 Inhibitors Apabetalone and JQ1 Rescues Endothelial Cells Dysfunction, Protects Monolayer Integrity and Reduces Midkine Expression. Molecules. 2022 Nov 2;27(21):7453. doi: 10.3390/molecules27217453. PMID: 36364277; PMCID: PMC9692972. 20: Gilham D, Smith AL, Fu L, Moore DY, Muralidharan A, Reid SPM, Stotz SC, Johansson JO, Sweeney M, Wong NCW, Kulikowski E, El-Gamal D. Bromodomain and Extraterminal Protein Inhibitor, Apabetalone (RVX-208), Reduces ACE2 Expression and Attenuates SARS-Cov-2 Infection In Vitro. Biomedicines. 2021 Apr 18;9(4):437. doi: 10.3390/biomedicines9040437. PMID: 33919584; PMCID: PMC8072876.