Israpafant

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]

Israpafant
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
ChemSpider
Chemical and physical data
FormulaC28H29ClN4S
Molar mass489.074 g/mol g·mol−1
3D model (JSmol)

See also

References
  1. Hirota, N; Yasuda, D; Hashidate, T; Yamamoto, T; Yamaguchi, S; Nagamune, T; Nagase, T; Shimizu, T; Nakamura, M (Feb 2010). "Amino acid residues critical for endoplasmic reticulum export and trafficking of platelet-activating factor receptor". Journal of Biological Chemistry. 285 (8): 5931–40. doi:10.1074/jbc.M109.066282. PMC 2820818. 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. PMID 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 Sci. 65 (13): PL171–6. doi:10.1016/s0024-3205(99)00385-9. PMID 10503965.
  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. Satoh, T; Tahara, E; Yamada, T; Watanabe, C; Itoh, T; Terasawa, K; Nagai, H; Saiki, I (Feb 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.
  7. Kawaguchi, A; Sugimoto, K; Fujimura, A (Jan 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. Chao, YY; Jan, CR (Jan 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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