WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 206449
CAS#: 149709-44-4
Description: Sacubitrilat, also known as LBQ-657, is endopeptidase inhibitor. 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.
MedKoo Cat#: 206449
Name: Sacubitrilat
CAS#: 149709-44-4
Chemical Formula: C22H25NO5
Exact Mass: 383.1733
Molecular Weight: 383.444
Elemental Analysis: C, 68.91; H, 6.57; N, 3.65; O, 20.86
Synonym: LBQ-657; LBQ 657; LBQ657; Sacubitrilat.
IUPAC/Chemical Name: (2R,4S)-5-([1,1'-biphenyl]-4-yl)-4-(3-carboxypropanamido)-2-methylpentanoic acid
InChi Key: DOBNVUFHFMVMDB-BEFAXECRSA-N
InChi Code: InChI=1S/C22H25NO5/c1-15(22(27)28)13-19(23-20(24)11-12-21(25)26)14-16-7-9-18(10-8-16)17-5-3-2-4-6-17/h2-10,15,19H,11-14H2,1H3,(H,23,24)(H,25,26)(H,27,28)/t15-,19+/m1/s1
SMILES Code: O=C(O)[C@H](C)C[C@H](NC(CCC(O)=O)=O)CC1=CC=C(C2=CC=CC=C2)C=C1
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
| Biological target: | Sacubitrilat (Desethyl Sacubitril) is an active neprilysin (NEP) inhibitor. |
| In vitro activity: | N/A |
| In vivo activity: | This study demonstrates that neprilysin inhibitor Sac directly improves Ca2+ homeostasis in human end‐stage HF by reducing pro‐arrhythmogenic SR Ca2+ leak without acutely affecting systolic Ca2+ release and inotropy. Reference: ESC Heart Fail. 2020 Oct;7(5):2992-3002. https://pubmed.ncbi.nlm.nih.gov/32710603/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMF | 30.0 | 78.24 | |
| DMSO | 77.0 | 200.81 | |
| Ethanol | 77.0 | 200.81 | |
| Ethanol:PBS (pH 7.2) (1:1) | 0.5 | 1.3 |
The following data is based on the product molecular weight 383.444 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. Eiringhaus J, Wünsche CM, Tirilomis P, Herting J, Bork N, Nikolaev VO, Hasenfuss G, Sossalla S, Fischer TH. Sacubitrilat reduces pro-arrhythmogenic sarcoplasmic reticulum Ca2+ leak in human ventricular cardiomyocytes of patients with end-stage heart failure. ESC Heart Fail. 2020 Oct;7(5):2992-3002. doi: 10.1002/ehf2.12918. Epub 2020 Jul 25. PMID: 32710603; PMCID: PMC7586991. |
| In vitro protocol: | N/A |
| In vivo protocol: | 1. Eiringhaus J, Wünsche CM, Tirilomis P, Herting J, Bork N, Nikolaev VO, Hasenfuss G, Sossalla S, Fischer TH. Sacubitrilat reduces pro-arrhythmogenic sarcoplasmic reticulum Ca2+ leak in human ventricular cardiomyocytes of patients with end-stage heart failure. ESC Heart Fail. 2020 Oct;7(5):2992-3002. doi: 10.1002/ehf2.12918. Epub 2020 Jul 25. PMID: 32710603; PMCID: PMC7586991. |
1: Gan L, Langenickel T, Petruck J, Kode K, Rajman I, Chandra P, Zhou W, Rebello S, Sunkara G. Effects of age and sex on the pharmacokinetics of LCZ696, an angiotensin receptor neprilysin inhibitor. J Clin Pharmacol. 2015 Jun 12. doi: 10.1002/jcph.571. [Epub ahead of print] PubMed PMID: 26073563.
2: Minguet J, Sutton G, Ferrero C, Gomez T, Bramlage P. LCZ696 : a new paradigm for the treatment of heart failure? Expert Opin Pharmacother. 2015 Feb;16(3):435-46. doi: 10.1517/14656566.2015.1000300. Review. PubMed PMID: 25597387.
3: von Lueder TG, Wang BH, Kompa AR, Huang L, Webb R, Jordaan P, Atar D, Krum H. Angiotensin receptor neprilysin inhibitor LCZ696 attenuates cardiac remodeling and dysfunction after myocardial infarction by reducing cardiac fibrosis and hypertrophy. Circ Heart Fail. 2015 Jan;8(1):71-8. doi: 10.1161/CIRCHEARTFAILURE.114.001785. Epub 2014 Oct 31. PubMed PMID: 25362207.
4: Gu J, Noe A, Chandra P, Al-Fayoumi S, Ligueros-Saylan M, Sarangapani R, Maahs S, Ksander G, Rigel DF, Jeng AY, Lin TH, Zheng W, Dole WP. Pharmacokinetics and pharmacodynamics of LCZ696, a novel dual-acting angiotensin receptor-neprilysin inhibitor (ARNi). J Clin Pharmacol. 2010 Apr;50(4):401-14. doi: 10.1177/0091270009343932. Epub 2009 Nov 23. PubMed PMID: 19934029.
