Israpafant

Israpafant

Israpafant

Chemical compound

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 thienotriazolodiazepine, 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 mobilize calcium transport.[8]

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See also

References

  1. [1]
    Hirota N, Yasuda D, Hashidate T, Yamamoto T, Yamaguchi S, Nagamune T, et al. (February 2010). "Amino acid residues critical for endoplasmic reticulum export and trafficking of platelet-activating factor receptor". The Journal of Biological Chemistry. 285 (8): 5931–40. doi:10.1074/jbc.M109.066282. PMC 2820818. PMID 20007715.
  2. [2]
    Hozawa S, Haruta Y, Ishioka S, Yamakido M (October 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 Pt 1): 1198–202. doi:10.1164/ajrccm.152.4.7551370. PMID 7551370.
  3. [3]
    Takehara S, Mikashima H, Muramoto Y, Terasawa M, Setoguchi M, Tahara T (December 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): 571–83. doi:10.1016/0090-6980(90)90002-D. PMID 1965554.
  4. [4]
    Komatsu H, Amano M, Yamaguchi S, Sugahara K (1999). "Inhibition of activation of human peripheral blood eosinophils by Y-24180, an antagonist to platelet-activating factor receptor". Life Sciences. 65 (13): PL171-6. doi:10.1016/s0024-3205(99)00385-9. PMID 10503965.
  5. [5]
    Mizuki M, Komatsu H, Akiyama Y, Iwane S, Tsuda T (1999). "Inhibition of eosinophil activation in bronchoalveolar lavage fluid from atopic asthmatics by Y-24180, an antagonist to platelet-activating factor". Life Sciences. 65 (20): 2031–9. doi:10.1016/s0024-3205(99)00470-1. PMID 10579457.
  6. [6]
    Satoh T, Tahara E, Yamada T, Watanabe C, Itoh T, Terasawa K, et al. (February 2000). "Differential effect of antiallergic drugs on IgE-mediated cutaneous reaction in passively sensitized mice". Pharmacology. 60 (2): 97–104. doi:10.1159/000028353. PMID 10657759. S2CID 6264992.
  7. [7]
    Kawaguchi A, Sugimoto K, Fujimura A (January 2001). "Preventive effect of platelet-activating factor antagonist, Y-24180, against cyclosporine-induced acute nephrotoxicity". Life Sciences. 68 (10): 1181–90. doi:10.1016/s0024-3205(00)01028-6. PMID 11228102.
  8. [8]
    Chao YY, Jan CR (January 2004). "Effect of Y-24180 on Ca2+ movement and proliferation in renal tubular cells". Life Sciences. 74 (7): 923–33. doi:10.1016/j.lfs.2003.09.033. PMID 14659980.
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