Licofelone

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Licofelone
Licofelone structure.svg
Legal status
Legal status
  • Investigational
Identifiers
  • [6-(4-Chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl]acetic acid
CAS Number
PubChem CID
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.222.821 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C23H22ClNO2
Molar mass 379.88 g·mol−1
  • InChI=1S/C23H22ClNO2/c1-23(2)13-19-22(15-6-4-3-5-7-15)21(16-8-10-17(24)11-9-16)18(12-20(26)27)25(19)14-23/h3-11H,12-14H2,1-2H3,(H,26,27) X mark.svgN
  • Key:UAWXGRJVZSAUSZ-UHFFFAOYSA-N X mark.svgN
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Licofelone is a dual COX/LOX inhibitor [1] [2] that was studied in clinical trials as a treatment for osteoarthritis [3] and which was under development by Merckle GmbH with partners Alfa Wassermann and Lacer.

Licofelone is both an analgesic and an anti-inflammatory. Inhibition of 5-lipoxygenase (5-LOX) may reduce the gastrointestinal toxicity associated with other nonsteroidal anti-inflammatory drugs (NSAID), which only inhibit cyclooxygenase (COX). Licofelone is the first drug to inhibit both.

Phase III trials for osteoarthritis were conducted in the early 2000s, [4] [5] but results were mixed and the drug has never been submitted for regulatory approval.

Related Research Articles

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<span class="mw-page-title-main">Nonsteroidal anti-inflammatory drug</span> Class of therapeutic drug for relieving pain and inflammation

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<span class="mw-page-title-main">Cyclooxygenase</span> Class of enzymes

Cyclooxygenase (COX), officially known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme that is responsible for biosynthesis of prostanoids, including thromboxane and prostaglandins such as prostacyclin, from arachidonic acid. A member of the animal-type heme peroxidase family, it is also known as prostaglandin G/H synthase. The specific reaction catalyzed is the conversion from arachidonic acid to prostaglandin H2 via a short-living prostaglandin G2 intermediate.

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<span class="mw-page-title-main">Mofezolac</span> Chemical compound

Mofezolac (INN), sold under the name Disopain in Japan, is a nonsteroidal anti-inflammatory drug (NSAID) used for its analgesic and anti-inflammatory actions. It is often prescribed for rheumatoid arthritis, lower back pain, frozen shoulder, and pain management after surgery or trauma. It is also being investigated for potential use in the treatment of neuroinflammation.

Cyclooxygenases are enzymes that take part in a complex biosynthetic cascade that results in the conversion of polyunsaturated fatty acids to prostaglandins and thromboxane(s). Their main role is to catalyze the transformation of arachidonic acid into the intermediate prostaglandin H2, which is the precursor of a variety of prostanoids with diverse and potent biological actions. Cyclooxygenases have two main isoforms that are called COX-1 and COX-2. COX-1 is responsible for the synthesis of prostaglandin and thromboxane in many types of cells, including the gastro-intestinal tract and blood platelets. COX-2 plays a major role in prostaglandin biosynthesis in inflammatory cells and in the central nervous system. Prostaglandin synthesis in these sites is a key factor in the development of inflammation and hyperalgesia. COX-2 inhibitors have analgesic and anti-inflammatory activity by blocking the transformation of arachidonic acid into prostaglandin H2 selectively.

<span class="mw-page-title-main">Polmacoxib</span> COX-2 selective NSAID medication

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<span class="mw-page-title-main">Otenaproxesul</span> Chemical compound

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An antiarthritic is any drug used to relieve or prevent arthritic symptoms, such as joint pain or joint stiffness. Depending on the antiarthritic drug class, it is used for managing pain, reducing inflammation or acting as an immunosuppressant. These drugs are typically given orally, topically or through administration by injection. The choice of antiarthritic medication is often determined by the nature of arthritis, the severity of symptoms as well as other factors, such as the tolerability of side effects.

References

  1. Fischer L, Hornig M, Pergola C, Meindl N, Franke L, Tanrikulu Y, et al. (October 2007). "The molecular mechanism of the inhibition by licofelone of the biosynthesis of 5-lipoxygenase products". British Journal of Pharmacology. 152 (4): 471–80. doi:10.1038/sj.bjp.0707416. PMC   2050828 . PMID   17704828.
  2. Vidal C, Gómez-Hernández A, Sánchez-Galán E, González A, Ortega L, Gómez-Gerique JA, et al. (January 2007). "Licofelone, a balanced inhibitor of cyclooxygenase and 5-lipoxygenase, reduces inflammation in a rabbit model of atherosclerosis". The Journal of Pharmacology and Experimental Therapeutics. 320 (1): 108–16. doi:10.1124/jpet.106.110361. PMID   17015640. S2CID   73105840.
  3. Alvaro-Gracia JM (February 2004). "Licofelone--clinical update on a novel LOX/COX inhibitor for the treatment of osteoarthritis". Rheumatology. 43 Suppl 1 (90001): i21-5. doi: 10.1093/rheumatology/keh105 . PMID   14752172.
  4. "Licofelone – Novel Analgesic and Anti-Inflammatory Agent for Osteoarthritis" . Retrieved January 12, 2018.
  5. Wildi LM, Raynauld JP, Martel-Pelletier J, Abram F, Dorais M, Pelletier JP (December 2010). "Relationship between bone marrow lesions, cartilage loss and pain in knee osteoarthritis: results from a randomised controlled clinical trial using MRI". Annals of the Rheumatic Diseases. 69 (12): 2118–24. doi:10.1136/ard.2009.127993. PMID   20610445. S2CID   206864399.