Varespladib

Varespladib
Clinical data
Pregnancy
category
ATC code none
Legal status
Legal status
  • investigational
Identifiers
CAS Number 172732-68-2 YesY
PubChem (CID) 155815
ChemSpider 137248 N
UNII 2Q3P98DATH YesY
KEGG D08107 N
ChEMBL CHEMBL148674 N
Chemical and physical data
Formula C21H20N2O5
Molar mass 380.4 g/mol
3D model (Jmol) Interactive image
 NYesY (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

Main article: varespladib methyl

Intravenous varespladib

Varespladib sodium
Clinical data
Pregnancy
category
Routes of
administration
IV
ATC code none
Legal status
Legal status
  • Investigational
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

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

  1. "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.
  2. "A-002: Short Term (16 week) Treatment of Acute Coronary Syndrome.". Anthera Pharmaceuticals. Retrieved 6 September 2011.
  3. "Varespladib". American Journal of Cardiovascular Drugs. 11 (2): 137–43. April 2011. doi:10.2165/11533650-000000000-00000. PMID 21446779.
  4. Baynes JW, Dominiczak MH (2005). Medical Biochemistry (2 ed.). Elsevier Mosby. p. 555. ISBN 0-7234-3341-0.
  5. 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.
  6. "Science: sPLA2". Anthera Pharmaceuticals. Retrieved 6 August 2011.
  7. 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.
  8. "A-001: Prevention of Acute Chest Syndrome in Sickle Cell Disease.". Anthera Pharmaceuticals. Retrieved 18 August 2011.
  9. 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.
  10. 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.
  11. 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.
  12. "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.
  13. ClinicalTrials.gov. "IMPACTS Trial: Investigation of the Modulation of Phospholipase in Acute Chest Syndrome.". United States National Institute of Health. Retrieved 18 August 2011.


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