Varespladib
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MedKoo CAT#: 522365

CAS#: 172732-68-2 (free acid)

Description: Varespladib, aslo known as LY315920, is a secreted phospholipase A2 (sPLA2) inhibitor (IC50 = 50 - 750 nM for a range of sPLA2 isoforms). Varespladib reduces atherosclerosis and aneurysm formation in ApoE-/- mice and in guinea pigs. Varespladib significantly reduces the post-ACS inflammatory response in those with and without diabetes. Varespladib may be potentially useful for treatment of coronary artery disease.


Chemical Structure

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Varespladib
CAS# 172732-68-2 (free acid)

Theoretical Analysis

MedKoo Cat#: 522365
Name: Varespladib
CAS#: 172732-68-2 (free acid)
Chemical Formula: C21H20N2O5
Exact Mass: 380.13722
Molecular Weight: 380.4
Elemental Analysis: C, 66.31; H, 5.30; N, 7.36; O, 21.03

Price and Availability

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5.0mg USD 150.0 Ready to ship
10.0mg USD 250.0 Ready to ship
25.0mg USD 550.0 Ready to ship
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Related CAS #: 172733-42-5 (sodium)   172732-68-2 (free acid)    

Synonym: LY315920; LY-315920; LY 315920; A-002; A002; A 002; Varespladib

IUPAC/Chemical Name: 2-((3-(2-amino-2-oxoacetyl)-1-benzyl-2-ethyl-1H-indol-4-yl)oxy)acetic acid

InChi Key: BHLXTPHDSZUFHR-UHFFFAOYSA-N

InChi Code: InChI=1S/C21H20N2O5/c1-2-14-19(20(26)21(22)27)18-15(9-6-10-16(18)28-12-17(24)25)23(14)11-13-7-4-3-5-8-13/h3-10H,2,11-12H2,1H3,(H2,22,27)(H,24,25)

SMILES Code: NC(C(C1=C(CC)N(CC2=CC=CC=C2)C3=C1C(OCC(O)=O)=CC=C3)=O)=O

Appearance: White to beige 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: Varespladib (LY315920) is a secretory phospholipase A2 (sPLA2) inhibitor with an IC50 of 9 nM.
In vitro activity: Varespladib was tested in vitro against pancreatic sPLA2 mixed with different albumin concentration. Varespladib was able to inhibit sPLA2 in the types of neonatal lung injury investigated. sPLA2 activity was reduced in hyaline membrane disease (P < .0001), infections (P = .003), and meconium aspiration (P = .04) using 40 µM varespladib; 10 µM was able to lower enzyme activity (P = .001), with an IC(50) of 87 µM. An inverse relationship existed between protein level and activity reduction (r = 0.5; P = .029). Reference: J Clin Pharmacol. 2012 May;52(5):729-37. https://accp1.onlinelibrary.wiley.com/doi/abs/10.1177/0091270011405498
In vivo activity: The effects of A-002 (Varespladib) on atherosclerosis was evaluated in 2 ApoE mouse models. In a high-fat diet model, A-002 (30 and 90 mg/kg twice a day for 16 weeks) reduced aortic atherosclerosis by 50% (P < 0.05). Plasma total cholesterol was decreased (P < 0.05) by 1 month and remained lowered throughout the study. In an accelerated atherosclerosis model, with angiotensin II-induced aortic lesions and aneurysms, A-002 (30 mg/kg twice a day) reduced aortic atherosclerosis by approximately 40% (P < 0.05) and attenuated aneurysm formation (P = 0.0096). Reference: J Cardiovasc Pharmacol. 2009 Jan;53(1):60-5. https://journals.lww.com/cardiovascularpharm/Abstract/2009/01000/Varespladib__A_002_,_a_Secretory_Phospholipase_A2.9.aspx

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 37.0 97.27
DMSO:PBS (pH 7.2) (1:1) 0.5 1.31
DMF 2.0 5.26
Ethanol 1.0 2.63

Preparing Stock Solutions

The following data is based on the product molecular weight 380.4 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. De Luca D, Minucci A, Trias J, Tripodi D, Conti G, Zuppi C, Capoluongo E; Study Group on Secretory Phospholipase in Pediatrics. Varespladib inhibits secretory phospholipase A2 in bronchoalveolar lavage of different types of neonatal lung injury. J Clin Pharmacol. 2012 May;52(5):729-37. doi: 10.1177/0091270011405498. Epub 2011 May 20. PMID: 21602519. 2. Fraser H, Hislop C, Christie RM, Rick HL, Reidy CA, Chouinard ML, Eacho PI, Gould KE, Trias J. Varespladib (A-002), a secretory phospholipase A2 inhibitor, reduces atherosclerosis and aneurysm formation in ApoE-/- mice. J Cardiovasc Pharmacol. 2009 Jan;53(1):60-5. doi: 10.1097/FJC.0b013e318195bfbc. PMID: 19129734.
In vitro protocol: 1. De Luca D, Minucci A, Trias J, Tripodi D, Conti G, Zuppi C, Capoluongo E; Study Group on Secretory Phospholipase in Pediatrics. Varespladib inhibits secretory phospholipase A2 in bronchoalveolar lavage of different types of neonatal lung injury. J Clin Pharmacol. 2012 May;52(5):729-37. doi: 10.1177/0091270011405498. Epub 2011 May 20. PMID: 21602519.
In vivo protocol: 1. Fraser H, Hislop C, Christie RM, Rick HL, Reidy CA, Chouinard ML, Eacho PI, Gould KE, Trias J. Varespladib (A-002), a secretory phospholipase A2 inhibitor, reduces atherosclerosis and aneurysm formation in ApoE-/- mice. J Cardiovasc Pharmacol. 2009 Jan;53(1):60-5. doi: 10.1097/FJC.0b013e318195bfbc. PMID: 19129734.

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1: Nicholls SJ, Kastelein JJ, Schwartz GG, Bash D, Rosenson RS, Cavender MA, Brennan DM, Koenig W, Jukema JW, Nambi V, Wright RS, Menon V, Lincoff AM, Nissen SE; VISTA-16 Investigators. Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial. JAMA. 2014 Jan 15;311(3):252-62. doi: 10.1001/jama.2013.282836. PubMed PMID: 24247616.

2: De Luca D, Vendittelli F, Trias J, Fraser H, Minucci A, Gentile L, Perez-Gil J, Conti G, Antonelli M, Capoluongo ED. Surfactant and varespladib co-administration in stimulated rat alveolar macrophages culture. Curr Pharm Biotechnol. 2013;14(4):445-8. PubMed PMID: 23590147.

3: De Luca D, Minucci A, Piastra M, Cogo PE, Vendittelli F, Marzano L, Gentile L, Giardina B, Conti G, Capoluongo ED. Ex vivo effect of varespladib on secretory phospholipase A2 alveolar activity in infants with ARDS. PLoS One. 2012;7(10):e47066. doi: 10.1371/journal.pone.0047066. Epub 2012 Oct 11. PubMed PMID: 23071714; PubMed Central PMCID: PMC3469496.

4: Rosenson RS, Fraser H, Goulder MA, Hislop C. Anti-inflammatory effects of varespladib methyl in diabetic patients with acute coronary syndrome. Cardiovasc Drugs Ther. 2011 Dec;25(6):539-44. doi: 10.1007/s10557-011-6344-2. PubMed PMID: 21989792.

5: De Luca D, Minucci A, Trias J, Tripodi D, Conti G, Zuppi C, Capoluongo E; Study Group on Secretory Phospholipase in Pediatrics. Varespladib inhibits secretory phospholipase A2 in bronchoalveolar lavage of different types of neonatal lung injury. J Clin Pharmacol. 2012 May;52(5):729-37. doi: 10.1177/0091270011405498. Epub 2011 May 20. PubMed PMID: 21602519.

6: Varespladib. Am J Cardiovasc Drugs. 2011;11(2):137-43. doi: 10.2165/11533650-000000000-00000. Review. PubMed PMID: 21446779.

7: Rosenson RS. After FRANCIS: next steps in the clinical evaluation of varespladib methyl. Future Cardiol. 2011 Jan;7(1):11-8. doi: 10.2217/fca.10.118. PubMed PMID: 21174506.

8: Arsenault BJ, Boekholdt SM, Kastelein JJ. Varespladib: targeting the inflammatory face of atherosclerosis. Eur Heart J. 2011 Apr;32(8):923-6. doi: 10.1093/eurheartj/ehq385. Epub 2010 Nov 25. PubMed PMID: 21112895.

9: Rosenson RS, Hislop C, Elliott M, Stasiv Y, Goulder M, Waters D. Effects of varespladib methyl on biomarkers and major cardiovascular events in acute coronary syndrome patients. J Am Coll Cardiol. 2010 Sep 28;56(14):1079-88. doi: 10.1016/j.jacc.2010.06.015. Erratum in: J Am Coll Cardiol. 2011 Mar 29;57(13):1501. PubMed PMID: 20863951.

10: Rosenson RS, Fraser H, Trias J, Hislop C. Varespladib methyl in cardiovascular disease. Expert Opin Investig Drugs. 2010 Oct;19(10):1245-55. doi: 10.1517/13543784.2010.517193. Review. PubMed PMID: 20809869.