Varespladib
Clinical data | |
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ATC code | none |
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Identifiers | |
CAS Number | 172732-68-2 |
PubChem (CID) | 155815 |
ChemSpider | 137248 |
UNII | 2Q3P98DATH |
KEGG | D08107 |
ChEMBL | CHEMBL148674 |
Chemical and physical data | |
Formula | C21H20N2O5 |
Molar mass | 380.4 g/mol |
3D model (Jmol) | Interactive image |
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(what is this?) |
Varespladib is an inhibitor of the IIa, V, and X isoforms of secretory phospholipase A2 (sPLA2).[1][2][3] The molecule acts as an anti-inflammatory agent by disrupting the first step of the arachidonic acid pathway of inflammation.[4] From 2006 to 2012, varespladib was under active investigation by Anthera Pharmaceuticals as a potential therapy for several inflammatory diseases, including acute coronary syndrome and acute chest syndrome.[5][6] The trial was halted in March 2012 due to inadequate efficacy.[7]
Oral varespladib
Intravenous varespladib
Clinical data | |
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Pregnancy category |
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Routes of administration | IV |
ATC code | none |
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Identifiers | |
Synonyms | A-001 |
CAS Number | 172733-42-5 |
PubChem (CID) | 23674730 |
ChemSpider | 137249 |
UNII | F6M52CDT0W |
KEGG | D06283 |
ChEMBL | CHEMBL2107809 |
Chemical and physical data | |
Formula | C21H19N2NaO5 |
Molar mass | 402.4 g/mol |
3D model (Jmol) | Interactive image |
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Varespladib sodium (also known as A-001, previously LY315920 and S-5920) is a sodium salt of varespladib designed for intravenous delivery.[8] It was under evaluation by Anthera Pharmaceuticals as an anti-inflammatory sPLA2 inhibitor for the prevention of acute chest syndrome (ACS), the leading cause of death for patients with sickle-cell disease.[5]
Elevated serum levels of sPLA2 have been observed in sickle-cell patients preceding and during ACS episodes. This profound elevation in sPLA2 levels is not observed in sickle-cell patients at steady-state or during a vaso-occlusive crisis, or in patients with respiratory diseases such as pneumonia.[9][10] A reduction in serum sPLA2 levels, for example through blood transfusion, reduces the risk of an ACS, suggesting that sPLA2 plays an important role in the onset of ACS.[11]
Anthera Pharmaceuticals acquired varespladib sodium from Lilly and Shionogi in 2006.[5] In 2007, the U.S. Food and Drug Administration (FDA) granted varespladib sodium orphan drug status for its potential to treat patients with sickle-cell disease.[12] In 2009, Anthera Pharmaceuticals completed a Phase II study of varespladib sodium in subjects with sickle cell disease at risk for ACS.[13]
References
- ↑ "Following Encouraging Results, Anthera to Continue IMACTS Trial for the Prevention of Acute Chest Syndrome in Patients with Sickle Cell Disease." (Press release). Anthera Pharmaceuticals, Inc. 24 March 2009.
- ↑ "A-002: Short Term (16 week) Treatment of Acute Coronary Syndrome.". Anthera Pharmaceuticals. Retrieved 6 September 2011.
- ↑ "Varespladib". American Journal of Cardiovascular Drugs. 11 (2): 137–43. April 2011. doi:10.2165/11533650-000000000-00000. PMID 21446779.
- ↑ Baynes JW, Dominiczak MH (2005). Medical Biochemistry (2 ed.). Elsevier Mosby. p. 555. ISBN 0-7234-3341-0.
- 1 2 3 "Anthera Licenses Portfolio of Anti-Inflammatory Products From Eli Lilly and Company and Shionogi & Co., Ltd." (Press release). Anthera Pharmaceuticals, Inc. 6 September 2006.
- ↑ "Science: sPLA2". Anthera Pharmaceuticals. Retrieved 6 August 2011.
- ↑ ClinicalTrials.gov. "VISTA-16 Trial: Evaluation of Safety and Efficacy of Short-term A-002 Treatment in Subjects With Acute Coronary Syndrome.". United States National Institute of Health. Retrieved 2011-08-17.
- ↑ "A-001: Prevention of Acute Chest Syndrome in Sickle Cell Disease.". Anthera Pharmaceuticals. Retrieved 18 August 2011.
- ↑ Styles LA, Schalkwijk CG, Aarsman AJ, Vichinsky EP, Lubin BH, Kuypers FA (March 1996). "Phospholipase A2 levels in acute chest syndrome of sickle cell disease." (PDF). Blood. 87 (6): 2573–78. PMID 8630425.
- ↑ Styles LA, Aarsman AJ, Vichinsky EP, Kuypers FA (November 2000). "Secretory phospholipase A(2) predicts impending acute chest syndrome in sickle cell disease". Blood. 96 (9): 3276–78. PMID 11050014.
- ↑ Bostrom M, Boyanovsky B, Jordan C, Wadsworth M, Taatjes D, de Beer F, et al. (March 2007). "Group v secretory phospholipase A2 promotes atherosclerosis: evidence from genetically altered mice.". Arteriosclerosis, Thrombosis, and Vascular Biology. 27 (3): 600–06. doi:10.1161/01.ATV.0000257133.60884.44. PMID 17204667.
- ↑ "Anthera's A-001 Receives Orphan Drug Status For The Prevention Of Acute Chest Syndrome In Patients With Sickle Cell Disease." (Press release). Anthera Pharmaceuticals, Inc. 18 December 2007.
- ↑ ClinicalTrials.gov. "IMPACTS Trial: Investigation of the Modulation of Phospholipase in Acute Chest Syndrome.". United States National Institute of Health. Retrieved 18 August 2011.
External links
- Varespladib methyl at Anthera.com
- Varespladib sodium at Anthera.com
- Varespladib methyl Phase III study at ClinicalTrials.gov
- Varespladib sodium Phase II study at ClinicalTrials.gov