Aliskiren Hemifumarate | CGP-060536B | CAS#173334-58-2 | renin inhibitor

MedKoo Cat#: 317166 | Name: Aliskiren Hemifumarate

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Description:

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

Aliskiren hemifumarate is a direct renin inhibitor. Aliskiren was approved by the US Food and Drug Administration (FDA) in March 2007, and in Europe in August 2007 for the treatment of hypertension (marketed as Tekturna and Rasilez, respectively).

Chemical Structure

Aliskiren Hemifumarate

CAS#173334-58-2 (hemifumarate)

Theoretical Analysis

MedKoo Cat#: 317166

Name: Aliskiren Hemifumarate

CAS#: 173334-58-2 (hemifumarate)

Chemical Formula: C30H53N3O6.1/2C4H4O4

Exact Mass: 0.0000

Molecular Weight: 609.83

Elemental Analysis:

Price and Availability

Size	Price	Availability
50mg	USD 250.00	2 weeks
100mg	USD 400.00	2 Weeks
250mg	USD 750.00	2 Weeks

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Related CAS #

173334-58-2 (hemifumarate) 173334-57-1 (free base)

Synonym

Aliskiren hemifumarate; CGP 060536B; CGP-060536B; CGP060536B; Rasilez; SPP100; Tekturna

IUPAC/Chemical Name

(αS,γS,δS,ζS)-δ-amino-N-(3-amino-2,2-dimethyl-3-oxopropyl)-γ-hydroxy-4-methoxy-3-(3-methoxypropoxy)-α,ζ-bis(1-methylethyl)-benzeneoctanamide, 2E-butenedioate

InChi Key

KLRSDBSKUSSCGU-KRQUFFFQSA-N

InChi Code

InChI=1S/2C30H53N3O6.C4H4O4/c2*1-19(2)22(14-21-10-11-26(38-8)27(15-21)39-13-9-12-37-7)16-24(31)25(34)17-23(20(3)4)28(35)33-18-30(5,6)29(32)36;5-3(6)1-2-4(7)8/h2*10-11,15,19-20,22-25,34H,9,12-14,16-18,31H2,1-8H3,(H2,32,36)(H,33,35);1-2H,(H,5,6)(H,7,8)

SMILES Code

COC1=C(OCCCOC)C=C(C[C@H](C(C)C)C[C@H](N)[C@@H](O)C[C@H](C(NCC(C)(C)C(N)=O)=O)C(C)C)C=C1.OC(/C=C/C(O)=O)=O

Appearance

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

Instruction

View handling instruction

Biological target:

Aliskiren hemifumarate(CGP 60536 hemifumarate) is a direct renin inhibitor with IC50 of 1.5 nM.

In vitro activity:

The human EPCs cultured for 7 days were pretreated with 1 μmol/L, 10 μmol/L, or 50 μmol/L aliskiren for 12 h. Treatment with aliskiren resulted in a dose-dependent increase in the migratory (Figure 3(a)) and proliferative (Figure 3(b)) activity of EPCs, respectively. Furthermore, aliskiren markedly enhanced the adhesion of EPCs (Figure 3(c)). Reference: Cardiol Res Pract. 2020; 2020: 6534512. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275222/

In vivo activity:

To investigate the cardioprotective effects of ALS (Aliskiren) on ISO-induced cardiac hypertrophy and fibrosis in vivo, a rat model of cardiac hypertrophy and fibrosis was successfully constructed. First, it was observed that ISO induced marked cardiac hypertrophy by increasing the cardiomyocyte width, which was significantly suppressed in the ALS+ISO treatment group (Figure 1A and B). In addition, both the ratio of heart weight to body weight (HW/BW) and LV weight to BW (LVW/BW) were increased following ISO injection, but HW/BW and LVW/BW were lowered in the combined ALS + ISO group (Figure 2A and B). Furthermore, the hypertrophic markers, including atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), α-myosin heavy chain (α-MHC) and β-myosin heavy chain (β-MHC), were evaluated in the LVs of rats. RT-qPCR analysis demonstrated that the levels of ANP, BNP, and β-MHC were significantly higher in the LVs from ISO-treated rats compared with the control group, but treatment with ALS significantly decreased the ISO-mediated increase in ANP, BNP, and β-MHC mRNA expression (Figure 2C, D and F). It was also observed that ISO treatment markedly decreased α-MHC mRNA expression. However, ALS treatment significantly reversed the ISO-induced downregulation of α-MHC in the LVs of rats (Figure 2E). Reference: Braz J Med Biol Res. 2020; 53(2): e8793. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6984373/

	Solvent	mg/mL	mM
Solubility
	DMSO	87.0	142.65
	Ethanol	100.0	163.98
	Water	77.8	127.49

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 609.83 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:

1. Yao S, Su C, Wu SH, Hu DJ, Liu X. Aliskiren Improved the Endothelial Repair Capacity of Endothelial Progenitor Cells from Patients with Hypertension via the Tie2/PI3k/Akt/eNOS Signalling Pathway. Cardiol Res Pract. 2020 May 28;2020:6534512. doi: 10.1155/2020/6534512. PMID: 32566272; PMCID: PMC7275222. 2. Chiang MH, Liang CJ, Liu CW, Pan BJ, Chen WP, Yang YF, Lee IT, Tsai JS, Lee CW, Chen YL. Aliskiren Improves Ischemia- and Oxygen Glucose Deprivation-Induced Cardiac Injury through Activation of Autophagy and AMP-Activated Protein Kinase. Front Pharmacol. 2017 Nov 14;8:819. doi: 10.3389/fphar.2017.00819. PMID: 29184499; PMCID: PMC5694452. 3. Essam M, Barakat N, Elkashef A, Awadalla A, Behery AE, Abdel-Maboud M. Functional and molecular evaluation of using aliskiren during acute and chronic partial ureteral obstruction in rat solitary kidney. Life Sci. 2021 Jan 15;265:118811. doi: 10.1016/j.lfs.2020.118811. Epub 2020 Nov 28. PMID: 33259867. 4. Zhao Z, Liu H, Guo D. Aliskiren attenuates cardiac dysfunction by modulation of the mTOR and apoptosis pathways. Braz J Med Biol Res. 2020 Jan 24;53(2):e8793. doi: 10.1590/1414-431X20198793. PMID: 31994601; PMCID: PMC6984373.

In vitro protocol:

In vivo protocol:

1. Essam M, Barakat N, Elkashef A, Awadalla A, Behery AE, Abdel-Maboud M. Functional and molecular evaluation of using aliskiren during acute and chronic partial ureteral obstruction in rat solitary kidney. Life Sci. 2021 Jan 15;265:118811. doi: 10.1016/j.lfs.2020.118811. Epub 2020 Nov 28. PMID: 33259867. 2. Zhao Z, Liu H, Guo D. Aliskiren attenuates cardiac dysfunction by modulation of the mTOR and apoptosis pathways. Braz J Med Biol Res. 2020 Jan 24;53(2):e8793. doi: 10.1590/1414-431X20198793. PMID: 31994601; PMCID: PMC6984373.

1: Kappert K, Unger T, Kintscher U. Aliskiren [Aliskiren hemifumarate]. Dtsch Med Wochenschr. 2008 Jun;133(24):1308-12. German. doi: 10.1055/s-2008-1077232. Epub 2008 May 9. PMID: 18465684. 2: Kunamaneni P, Kovvasu S, Yeung S, Wang J, Shah S, Betageri G. Aliskiren Hemifumarate Proliposomes for Improved Oral Drug Delivery: Formulation Development, In Vitro and In Vivo Permeability Testing. Molecules. 2022 Jul 28;27(15):4828. doi: 10.3390/molecules27154828. PMID: 35956779; PMCID: PMC9369865. 3: Ali AK. Pharmacovigilance analysis of adverse event reports for aliskiren hemifumarate, a first-in-class direct renin inhibitor. Ther Clin Risk Manag. 2011;7:337-44. doi: 10.2147/TCRM.S23889. Epub 2011 Aug 9. PMID: 21941439; PMCID: PMC3176166. 4: Salim MM, Ebeid WM, El-Enany N, Belal F, Walash M, Patonay G. Simultaneous determination of aliskiren hemifumarate, amlodipine besylate, and hydrochlorothiazide in their triple mixture dosage form by capillary zone electrophoresis. J Sep Sci. 2014 May;37(9-10):1206-13. doi: 10.1002/jssc.201301140. Epub 2014 Mar 25. PMID: 24574149. 5: Ebeid WM, Elkady EF, El-Zaher AA, El-Bagary RI, Patonay G. Simultaneous Determination of Aliskiren Hemifumarate, Amlodipine Besylate and Hydrochlorothiazide in Spiked Human Plasma Using UPLC-MS/MS. J Chromatogr Sci. 2015 Aug;53(7):1178-84. doi: 10.1093/chromsci/bmu213. Epub 2015 Jan 9. PMID: 25575509. 6: Hussar DA. New drugs: aliskiren hemifumarate, lisdexamfetamine dimesylate, and lapatinib. J Am Pharm Assoc (2003). 2007 May-Jun;47(3):425-6, 428-30. doi: 10.1331/JAPhA.2007.07504. PMID: 17510042. 7: Anwer MK, Muqtader M, Iqbal M, Ali R, Almutairy BK, Alshetaili A, Alshahrani SM, Aldawsari MF, Alalaiwe A, Shakeel F. Estimating the Solubility, Solution Thermodynamics, and Molecular Interaction of Aliskiren Hemifumarate in Alkylimidazolium Based Ionic Liquids. Molecules. 2019 Aug 1;24(15):2807. doi: 10.3390/molecules24152807. PMID: 31374890; PMCID: PMC6695967. 8: Ashok S, Varma MS, Swaminathan S. A validated LC method for the determination of the enantiomeric purity of aliskiren hemifumarate in bulk drug samples. J Chromatogr Sci. 2012 Oct;50(9):799-802. doi: 10.1093/chromsci/bms073. Epub 2012 Jun 24. PMID: 22732253. 9: Ebeid WM, Elkady EF, El-Zaher AA, El-Bagary RI, Patonay G. Steady-state and synchronous spectrofluorimetric methods for simultaneous determination of aliskiren hemifumarate and amlodipine besylate in dosage forms. Luminescence. 2014 Nov;29(7):878-83. doi: 10.1002/bio.2636. Epub 2014 Mar 31. PMID: 24687516. 10: Özdemir FA, Akyüz A. Simultaneous determination of amlodipine and aliskren in tablets by high-performance liquid chromatography. J Chromatogr Sci. 2014 Aug;52(7):685-90. doi: 10.1093/chromsci/bmt099. Epub 2013 Jul 9. PMID: 23839804. 11: Burckhardt BB, Tins J, Ramusovic S, Läer S. Tailored Assays for Pharmacokinetic and Pharmacodynamic Investigations of Aliskiren and Enalapril in Children: An Application in Serum, Urine, and Saliva. J Pediatr Pharmacol Ther. 2015 Nov-Dec;20(6):431-52. doi: 10.5863/1551-6776-20.6.431. PMID: 26766933; PMCID: PMC4708953. 12: Waldmeier F, Glaenzel U, Wirz B, Oberer L, Schmid D, Seiberling M, Valencia J, Riviere GJ, End P, Vaidyanathan S. Absorption, distribution, metabolism, and elimination of the direct renin inhibitor aliskiren in healthy volunteers. Drug Metab Dispos. 2007 Aug;35(8):1418-28. doi: 10.1124/dmd.106.013797. Epub 2007 May 17. PMID: 17510248. 13: Janek K, Niewienda A, Wöstemeyer J, Voigt J. The cleavage specificity of the aspartic protease of cocoa beans involved in the generation of the cocoa- specific aroma precursors. Food Chem. 2016 Nov 15;211:320-8. doi: 10.1016/j.foodchem.2016.05.033. Epub 2016 May 13. PMID: 27283639. 14: Moussa BA, El-Zaher AA, Mahrouse MA, Ahmed MS. Resolution of overlapped spectra for the determination of ternary mixture using different and modified spectrophotometric methods. Spectrochim Acta A Mol Biomol Spectrosc. 2016 Aug 5;165:127-137. doi: 10.1016/j.saa.2016.04.003. Epub 2016 Apr 7. PMID: 27128521. 15: Ebeid WM, Elkady EF, El-Zaher AA, El-Bagary RI, Patonay G. Synchronized separation of seven medications representing most commonly prescribed antihypertensive classes by using reversed-phase liquid chromatography: Application for analysis in their combined formulations. J Sep Sci. 2014 Apr;37(7):748-57. doi: 10.1002/jssc.201301298. Epub 2014 Mar 7. PMID: 24482404.