Israpafant

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Israpafant
Israpafant.svg
Systematic (IUPAC) name
4-(2-Chlorophenyl)-6,9-dimethyl-2-[2-[4-(2-methylpropyl)phenyl]ethyl]-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine
Clinical data
Legal status
  • Investigational New Drug
Identifiers
CAS Registry Number 117279-73-9 YesY
PubChem CID: 636426
ChemSpider 552203
Chemical data
Formula C28H29ClN4S
Molecular mass 489.074

Israpafant (Y-24180) is a drug which acts as a selective antagonist for the platelet-activating factor receptor,[1] and was originally developed for the treatment of asthma.[2] Its chemical structure is a triazolothienodiazepine, closely related to the sedative benzodiazepine derivative etizolam. However israpafant binds far more tightly to the platelet-activating factor receptor, with an IC50 of 0.84nM for inhibiting PAF-induced human platelet aggregation (compared to etizolam's IC50 of 998nM at this target), while it binds only weakly to benzodiazepine receptors, with a Ki of 3680nM.[3] Israpafant has been found to inhibit the activation of eosinophil cells,[4][5][6] and consequently delays the development of immune responses. It has also been shown to have anti-nephrotoxic properties,[7] and to mobilise calcium transport.[8]


See also[edit]

References[edit]

  1. ^ Hirota N, Yasuda D, Hashidate T, Yamamoto T, Yamaguchi S, Nagamune T, Nagase T, Shimizu T, Nakamura M. Amino acid residues critical for endoplasmic reticulum export and trafficking of platelet-activating factor receptor. Journal of Biological Chemistry. 2010 Feb 19;285(8):5931-40. doi: 10.1074/jbc.M109.066282. PMID 20007715
  2. ^ Hozawa, S (1995). "Effects of a PAF antagonist, Y-24180, on bronchial hyperresponsiveness in patients with asthma.". American Journal of Respiratory and Critical Care Medicine 152 (4): 1198–1202. doi:10.1164/ajrccm.152.4.7551370. 
  3. ^ Takehara, S. (1990). "Pharmacological actions of Y-24180, a new specific antagonist of Platelet Activating Factor (PAF): II. Interactions with PAF and benzodiazepine receptors". Prostaglandins 40 (6): 571–583. doi:10.1016/0090-6980(90)90002-D. 
  4. ^ Komatsu H, Amano M, Yamaguchi S, Sugahara K. Inhibition of activation of human peripheral blood eosinophils by Y-24180, an antagonist to platelet-activating factor receptor. Life Sciences. 1999;65(13):PL171-6. PMID 10503965
  5. ^ Mizuki M, Komatsu H, Akiyama Y, Iwane S, Tsuda T. Inhibition of eosinophil activation in bronchoalveolar lavage fluid from atopic asthmatics by Y-24180, an antagonist to platelet-activating factor. Life Sciences. 1999;65(20):2031-9. PMID 10579457
  6. ^ Satoh T, Tahara E, Yamada T, Watanabe C, Itoh T, Terasawa K, Nagai H, Saiki I. Differential effect of antiallergic drugs on IgE-mediated cutaneous reaction in passively sensitized mice. Pharmacology. 2000 Feb;60(2):97-104. PMID 10657759
  7. ^ Kawaguchi A, Sugimoto K, Fujimura A. Preventive effect of platelet-activating factor antagonist, Y-24180, against cyclosporine-induced acute nephrotoxicity. Life Sciences. 2001 Jan 26;68(10):1181-90. PMID 11228102
  8. ^ Chao YY, Jan CR. Effect of Y-24180 on Ca2+ movement and proliferation in renal tubular cells. Life Sciences. 2004 Jan 2;74(7):923-33. PMID 14659980