MedKoo Biosciences, Inc.
Tel:   +1-919-636-5577    Fax:   +1-919-980-4831    Email:   sales@medkoo.com
Search
Login Register
Search
MedKoo Cat#: 314262 | Name: Sacubitril calcium salt
Featured New

Description:

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

Sacubitril, also known as AHU377, is angiotensin receptor neprilysin inhibitor being studied for use in combination with valsartan for heart failure. Sacubitril is a prodrug that is activated to LBQ657 by de-ethylation via esterases. LBQ657 inhibits the enzyme neprilysin, which is responsible for the degradation of atrial and brain natriuretic peptide, two blood pressure lowering peptides that work mainly by reducing blood volume.

Chemical Structure

Sacubitril calcium salt
Sacubitril calcium salt
CAS#1369773-39-6 (hemi-calcium)

Theoretical Analysis

MedKoo Cat#: 314262

Name: Sacubitril calcium salt

CAS#: 1369773-39-6 (hemi-calcium)

Chemical Formula: C48H56CaN2O10

Exact Mass: 0.0000

Molecular Weight: 861.06

Elemental Analysis: C, 66.96; H, 6.56; Ca, 4.65; N, 3.25; O, 18.58

Price and Availability

Size Price Availability Quantity
200mg USD 150.00 Ready to ship
1g USD 350.00 Ready to ship
2g USD 550.00 Ready to ship
5g USD 1,150.00 Ready to ship
10g USD 2,050.00 Ready to ship
Bulk Inquiry
Buy Now
Add to Cart
Related CAS #
1369773-39-6 (hemi-calcium) 149709-62-6 (free acid) 149690-05-1 (sodium) 936623-90-4 (Valsarta + sacubitril) 936623-90-4 137862-53-4
Synonym
AHU337; AHU-337; AHU 337; LCZ696; LCZ 696; LCZ696; Sacubitril; Entresto.
IUPAC/Chemical Name
calcium 4-(((2S,4R)-1-([1,1'-biphenyl]-4-yl)-5-ethoxy-4-methyl-5-oxopentan-2-yl)amino)-4-oxobutanoate
InChi Key
DDLCKLBRBPYKQS-OXXXZDCLSA-L
InChi Code
InChI=1S/2C24H29NO5.Ca/c2*1-3-30-24(29)17(2)15-21(25-22(26)13-14-23(27)28)16-18-9-11-20(12-10-18)19-7-5-4-6-8-19;/h2*4-12,17,21H,3,13-16H2,1-2H3,(H,25,26)(H,27,28);/q;;+2/p-2/t2*17-,21+;/m11./s1
SMILES Code
O=C(CCC(N[C@H](CC1=CC=C(C=C1)C2=CC=CC=C2)C[C@H](C(OCC)=O)C)=O)[O-].O=C(CCC(N[C@H](CC3=CC=C(C=C3)C4=CC=CC=C4)C[C@H](C(OCC)=O)C)=O)[O-].[Ca+2]
Appearance
white to off-white solid powder
Purity
>99% (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 (10 mg/mL) and in ethanol (5mg/mL).
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO or water
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
Sacubitril is an antihypertensive drug used in combination with valsartan. The combination drug, valsartan/sacubitril, known during trials as LCZ696 and marketed under the brand name, Entresto, is a treatment for heart failure. It was approved under the FDA's priority review process for use in heart failure on July 7, 2015. Sacubitril is a prodrug that is activated to LBQ657 by de-ethylation via esterases. LBQ657 inhibits the enzyme neprilysin, which is responsible for the degradation of atrial and brain natriuretic peptide, two blood pressure lowering peptides that work mainly by reducing blood volume. (source: https://en.wikipedia.org/wiki/Sacubitril).
Biological target:
Sacubitril hemicalcium salt (AHU-377 hemicalcium salt) is a potent NEP inhibitor with an IC50 of 5 nM.
In vitro activity:
In vitro incubation studies revealed that sacubitril is hydrolyzed by the liver, but not by the intestines, kidneys, or plasma, indicating that sacubitril is selectively activated by hepatic CES1. This conclusion is further supported by the observations that sacubitril was efficiently activated by purified recombinant CES1, but not CES2. Reference: Drug Metab Dispos. 2016 Apr;44(4):554-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810765/
In vivo activity:
LCZ696 (sacubitril/valsartan) and valsartan dose dependently prolonged the survival of these animals, and the effect of LCZ696-(30 mg/kg) was significantly greater than that of valsartan-(15 mg/kg). In this study, LCZ696 and valsartan dose dependently reduced urinary protein excretion in rats with subtotal nephrectomy, and the effect of LCZ696-(30 mg/kg) was significantly greater than that of valsartan-(15 mg/kg). In addition, compared to the vehicle group, glomerular sclerosis was significantly alleviated in the LCZ696-(30 mg/kg), but not the valsartan-(15 mg/kg) groups at 8 weeks in Experiment 2. Reference: Pharmacol Res Perspect. 2017 Aug; 5(4): e00336. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5684857/
Solvent mg/mL mM
Solubility
DMSO 72.0 83.63
DMSO:PBS (pH 7.2) (1:3) 0.3 0.29
DMF 20.0 23.23
Ethanol 6.8 7.91
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 861.06 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.

Recalculate based on batch purity %
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. Burke RM, Lighthouse JK, Mickelsen DM, Small EM. Sacubitril/Valsartan Decreases Cardiac Fibrosis in Left Ventricle Pressure Overload by Restoring PKG Signaling in Cardiac Fibroblasts. Circ Heart Fail. 2019 Apr;12(4):e005565. doi: 10.1161/CIRCHEARTFAILURE.118.005565. PMID: 30998392; PMCID: PMC6530564. 2. Shi J, Wang X, Nguyen J, Wu AH, Bleske BE, Zhu HJ. Sacubitril Is Selectively Activated by Carboxylesterase 1 (CES1) in the Liver and the Activation Is Affected by CES1 Genetic Variation. Drug Metab Dispos. 2016 Apr;44(4):554-9. doi: 10.1124/dmd.115.068536. Epub 2016 Jan 27. PMID: 26817948; PMCID: PMC4810765. 3. Ushijima K, Ando H, Arakawa Y, Aizawa K, Suzuki C, Shimada K, Tsuruoka SI, Fujimura A. Prevention against renal damage in rats with subtotal nephrectomy by sacubitril/valsartan (LCZ696), a dual-acting angiotensin receptor-neprilysin inhibitor. Pharmacol Res Perspect. 2017 Aug;5(4):e00336. doi: 10.1002/prp2.336. PMID: 28805977; PMCID: PMC5684857. 4. Seki T, Goto K, Kansui Y, Ohtsubo T, Matsumura K, Kitazono T. Angiotensin II Receptor-Neprilysin Inhibitor Sacubitril/Valsartan Improves Endothelial Dysfunction in Spontaneously Hypertensive Rats. J Am Heart Assoc. 2017 Oct 17;6(10):e006617. doi: 10.1161/JAHA.117.006617. PMID: 29042424; PMCID: PMC5721864.
In vitro protocol:
1. Burke RM, Lighthouse JK, Mickelsen DM, Small EM. Sacubitril/Valsartan Decreases Cardiac Fibrosis in Left Ventricle Pressure Overload by Restoring PKG Signaling in Cardiac Fibroblasts. Circ Heart Fail. 2019 Apr;12(4):e005565. doi: 10.1161/CIRCHEARTFAILURE.118.005565. PMID: 30998392; PMCID: PMC6530564. 2. Shi J, Wang X, Nguyen J, Wu AH, Bleske BE, Zhu HJ. Sacubitril Is Selectively Activated by Carboxylesterase 1 (CES1) in the Liver and the Activation Is Affected by CES1 Genetic Variation. Drug Metab Dispos. 2016 Apr;44(4):554-9. doi: 10.1124/dmd.115.068536. Epub 2016 Jan 27. PMID: 26817948; PMCID: PMC4810765.
In vivo protocol:
1. Ushijima K, Ando H, Arakawa Y, Aizawa K, Suzuki C, Shimada K, Tsuruoka SI, Fujimura A. Prevention against renal damage in rats with subtotal nephrectomy by sacubitril/valsartan (LCZ696), a dual-acting angiotensin receptor-neprilysin inhibitor. Pharmacol Res Perspect. 2017 Aug;5(4):e00336. doi: 10.1002/prp2.336. PMID: 28805977; PMCID: PMC5684857. 2. Seki T, Goto K, Kansui Y, Ohtsubo T, Matsumura K, Kitazono T. Angiotensin II Receptor-Neprilysin Inhibitor Sacubitril/Valsartan Improves Endothelial Dysfunction in Spontaneously Hypertensive Rats. J Am Heart Assoc. 2017 Oct 17;6(10):e006617. doi: 10.1161/JAHA.117.006617. PMID: 29042424; PMCID: PMC5721864.
1: Fabris E, Merlo M, Rapezzi C, Ferrari R, Metra M, Frigerio M, Sinagra G. Sacubitril/Valsartan: Updates and Clinical Evidence for a Disease-Modifying Approach. Drugs. 2019 Sep;79(14):1543-1556. doi: 10.1007/s40265-019-01181-2. Review. PubMed PMID: 31432436. 2: Dewan P, Docherty KF, McMurray JJV. Sacubitril/Valsartan in Asian Patients with Heart Failure with Reduced Ejection Fraction. Korean Circ J. 2019 Jun;49(6):469-484. doi: 10.4070/kcj.2019.0136. Review. PubMed PMID: 31172710; PubMed Central PMCID: PMC6554586. 3: De Vecchis R, Ariano C. Vasodilatory Properties of Sacubitril/Valsartan Explored in Hypertensives Aged Over 55 Years: A Meta-Analysis. High Blood Press Cardiovasc Prev. 2019 Apr 1. doi: 10.1007/s40292-019-00313-9. [Epub ahead of print] Review. PubMed PMID: 30937854. 4: Fonseca C, Brito D, Ferreira J, Franco F, Morais J, Silva Cardoso J; Experts opinion, endorsed by the Working Group on Heart Failure of the Portuguese Society of cardiology. Sacubitril/valsartan: A practical guide. Rev Port Cardiol. 2019 May;38(5):309-313. doi: 10.1016/j.repc.2018.10.008. Epub 2019 Jan 22. Review. English, Portuguese. PubMed PMID: 30679005. 5: Sauer AJ, Cole R, Jensen BC, Pal J, Sharma N, Yehya A, Vader J. Practical guidance on the use of sacubitril/valsartan for heart failure. Heart Fail Rev. 2019 Mar;24(2):167-176. doi: 10.1007/s10741-018-9757-1. Review. PubMed PMID: 30565021; PubMed Central PMCID: PMC6394573. 6: Gori M, D'Elia E, Senni M. Sacubitril/valsartan therapeutic strategy in HFpEF: Clinical insights and perspectives. Int J Cardiol. 2019 Apr 15;281:158-165. doi: 10.1016/j.ijcard.2018.06.060. Epub 2018 Nov 9. Review. PubMed PMID: 30420146. 7: Huet F, Akodad M, Kalmanovitch E, Adda J, Agullo A, Batistella P, Roubille C, Roubille F. Potential Uses of Sacubitril/Valsartan: Need for Data on Efficacy and Safety. Am J Cardiovasc Drugs. 2019 Feb;19(1):1-10. doi: 10.1007/s40256-018-0306-z. Review. PubMed PMID: 30345485. 8: Baliga RR. Sacubitril/Valsartan: The Newest Neurohormonal Blocker for Guideline-Directed Medical Therapy for Heart Failure. Heart Fail Clin. 2018 Oct;14(4):479-491. doi: 10.1016/j.hfc.2018.06.012. Epub 2018 Aug 17. Review. PubMed PMID: 30266357. 9: Dargad RR, Prajapati MR, Dargad RR, Parekh JD. Sacubitril/valsartan: A novel angiotensin receptor-neprilysin inhibitor. Indian Heart J. 2018 Jul;70 Suppl 1:S102-S110. doi: 10.1016/j.ihj.2018.01.002. Epub 2018 Jan 8. Review. PubMed PMID: 30122239; PubMed Central PMCID: PMC6097164. 10: Anderson SL, Marrs JC. Sacubitril/valsartan: evaluation of safety and efficacy as an antihypertensive treatment. Drugs Context. 2018 Aug 6;7:212542. doi: 10.7573/dic.212542. eCollection 2018. Review. PubMed PMID: 30116284; PubMed Central PMCID: PMC6089617. 11: Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006-. Available from http://www.ncbi.nlm.nih.gov/books/NBK500875/ PubMed PMID: 29999934. 12: Das BB, Scholl F, Vandale B, Chrisant M. Sacubitril/Valsartan: potential treatment for paediatric heart failure. Cardiol Young. 2018 Sep;28(9):1077-1081. doi: 10.1017/S1047951118001014. Epub 2018 Jul 6. Review. PubMed PMID: 29979147. 13: Nicolas D, Reed M. Sacubitril/Valsartan. 2019 Oct 17. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK507904/ PubMed PMID: 29939681. 14: Yandrapalli S, Khan MH, Rochlani Y, Aronow WS. Sacubitril/valsartan in cardiovascular disease: evidence to date and place in therapy. Ther Adv Cardiovasc Dis. 2018 Aug;12(8):217-231. doi: 10.1177/1753944718784536. Epub 2018 Jun 19. Review. PubMed PMID: 29921166; PubMed Central PMCID: PMC6041873. 15: Sciatti E, Senni M, Lombardi CM, Gori M, Metra M. Sacubitril/valsartan: from a large clinical trial to clinical practice. J Cardiovasc Med (Hagerstown). 2018 Sep;19(9):473-479. doi: 10.2459/JCM.0000000000000687. Review. PubMed PMID: 29917003. 16: Liu RC. Focused Treatment of Heart Failure with Reduced Ejection Fraction Using Sacubitril/Valsartan. Am J Cardiovasc Drugs. 2018 Dec;18(6):473-482. doi: 10.1007/s40256-018-0280-5. Review. PubMed PMID: 29850980; PubMed Central PMCID: PMC6267534. 17: Joly JM, Desai AS. Sacubitril/Valsartan: From Clinical Trials to Real-world Experience. Curr Treat Options Cardiovasc Med. 2018 Apr 23;20(6):45. doi: 10.1007/s11936-018-0638-7. Review. PubMed PMID: 29687191. 18: Kario K. The Sacubitril/Valsartan, a First-in-Class, Angiotensin Receptor Neprilysin Inhibitor (ARNI): Potential Uses in Hypertension, Heart Failure, and Beyond. Curr Cardiol Rep. 2018 Jan 27;20(1):5. doi: 10.1007/s11886-018-0944-4. Review. PubMed PMID: 29374807. 19: Zaid Iskandar M, Lang CC. Sacubitril and valsartan fixed combination to reduce heart failure events in post-acute myocardial infarction patients. Drugs Today (Barc). 2017 Oct;53(10):545-551. doi: 10.1358/dot.2017.53.10.2722396. Review. PubMed PMID: 29286056. 20: Institute for Quality and Efficiency in Health Care. Sacubitril / Valsartan -- Benefit Assessment According to §35a Social Code Book V [Internet]. Cologne, Germany: Institute for Quality and Efficiency in Health Care (IQWiG); 2016 Mar 30. Available from http://www.ncbi.nlm.nih.gov/books/NBK458434/ PubMed PMID: 29144684.

View History

Decarestrictine D

Decarestrictine D

HY17541A

HY17541A

Froxiprost

Froxiprost