Matsumoto Norimasa, Kohno Takeyuki, Uchida Shuji, Shimizu Takaaki, Kusumoto Haruko, Hirose Ryoji, Yanada Kazuo, Kurio Wasako, Yamaguchi Shoji, Watabe Kazuhito, Fujita Tetsuro
Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka 573-0101, Japan.
Bioorg Med Chem. 2006 Jun 15;14(12):4182-92. doi: 10.1016/j.bmc.2006.01.071. Epub 2006 Feb 28.
FTY720 (1) is a novel immunosuppressant (immunomodulator), derived from ISP-I (2: myriocin and thermozymocidin). To clarify the pharmacokinetic properties of 1, antibodies against 1 were prepared and a competitive enzyme immunoassay (EIA) was developed. Two kinds of haptens, 3 and 4, for 1 were synthesized and coupled to ovalbumin (OVA). Rabbits were immunized with 3-OVA or 4-OVA, and corresponding antibodies were obtained. Both antibodies recognized the 2-amino-2-(2-phenylethyl)propane-1,3-diol moiety in 1. Using the anti-3-OVA antibody, a competitive EIA for 1 was developed and evaluated. The range of quantification by the EIA was 0.06-10 ng/mL. The application of the EIA has enabled us to measure the FTY720 concentration in serum after oral administration of 1 (1mg/kg) to rats.
FTY720 (1) 是一种新型免疫抑制剂（免疫调节剂），由ISP-I（2：麦立若菌素和嗜热栖热放线菌素）衍生而来。为阐明1的药代动力学特性，制备了针对1的抗体并开发了竞争性酶免疫测定法（EIA）。合成了两种针对1的半抗原3和4，并将其与卵清蛋白（OVA）偶联。用3-OVA或4-OVA免疫兔子，获得了相应抗体。两种抗体均识别1中的2-氨基-2-(2-苯乙基)丙烷-1,3-二醇部分。使用抗3-OVA抗体，开发并评估了1的竞争性EIA。EIA的定量范围为0.06-10 ng/mL。EIA的应用使我们能够测量大鼠口服1（1mg/kg）后血清中的FTY720浓度。
