Sandbox Reserved 1105: Difference between revisions
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=== Non-steroidal anti-inflammatory drugs=== | === Non-steroidal anti-inflammatory drugs=== | ||
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[[Image:nat_lig.jpg|thumb|left|alt=Puzzle globe|Caption for the image|Structures of thyroxine (T4), the natural ligand of TTR and other designed TTR fibril formation inhibitors|200px]] | |||
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The fibril formation inhibitors studied are ligands that resemble to the natural ligand T4 but more efficient in binding TTR, leading to a decrease of the amyloidogenic potential. The first potent amyloid inhibitors developed were non-steroidal anti-inflammatory drugs (NSAID), such as flufenamic acid ([[1bm7]]), resveratrol ([[1dvs]]), diclofenac ([[1dvx]]), flurbiprofen ([[1dvt]]), indomethacin, diflunisal, meclofenamic acid, mefenamic acid, or fenoprofen. | The fibril formation inhibitors studied are ligands that resemble to the natural ligand T4 but more efficient in binding TTR, leading to a decrease of the amyloidogenic potential. The first potent amyloid inhibitors developed were non-steroidal anti-inflammatory drugs (NSAID), such as flufenamic acid ([[1bm7]]), resveratrol ([[1dvs]]), diclofenac ([[1dvx]]), flurbiprofen ([[1dvt]]), indomethacin, diflunisal, meclofenamic acid, mefenamic acid, or fenoprofen. | ||
However, regardless of a noticeable decrease of the TTR’s amyloidogenic potential <ref name="Klabunde" />, prolonged NSAIDs administration could provoke renal failure, cardiac side effects, and gastrointestinal ulcers. <ref>Bally, M; Dendukuri, N; Rich, B; Nadeau, L; Helin-Salmivaara, A; Garbe, E; Brophy, JM (9 May 2017). "Risk of acute myocardial infarction with NSAIDs in real world use: bayesian meta-analysis of individual patient data". BMJ (Clinical Research Ed.). 357: j1909. PMC 5423546. PMID 28487435 doi: http://dx.doi.org/10.1136/bmj.j1909</ref> Gastric toxicity is linked to NSAID’s binding to a [[cyclooxygenase]] isoform, resulting in an inhibition of the activity of COX-1 and/or COX-2 associated to prostaglandin’s negative regulation. <ref name="Klabunde" /> | However, regardless of a noticeable decrease of the TTR’s amyloidogenic potential <ref name="Klabunde" />, prolonged NSAIDs administration could provoke renal failure, cardiac side effects, and gastrointestinal ulcers. <ref>Bally, M; Dendukuri, N; Rich, B; Nadeau, L; Helin-Salmivaara, A; Garbe, E; Brophy, JM (9 May 2017). "Risk of acute myocardial infarction with NSAIDs in real world use: bayesian meta-analysis of individual patient data". BMJ (Clinical Research Ed.). 357: j1909. PMC 5423546. PMID 28487435 doi: http://dx.doi.org/10.1136/bmj.j1909</ref> Gastric toxicity is linked to NSAID’s binding to a [[cyclooxygenase]] isoform, resulting in an inhibition of the activity of COX-1 and/or COX-2 associated to prostaglandin’s negative regulation. <ref name="Klabunde" /> | ||