YM-90709 is a new-type antagonist inhibiting the binding of interleukin-5 to the interleukin-5 receptor.

YM-90709 强效抑制了 100 pM [125I]-IL-5 与人外周嗜酸性粒细胞和嗜酸性HL-60克隆15细胞上的IL-5R的结合，其IC50值分别为1.0±0.40 μM和0.57±0.21 μM。YM-90709以浓度依赖性方式抑制4 pM IL-5诱导的效应，IC50值为0.45±0.024 μM。同时，YM-90709还能抑制高浓度(12 和 40 pM)IL-5诱导的效应，其IC50值分别为0.89±0.29 μM和1.0±0.22 μM。[1] 作为一种新型的白细胞介素-5受体拮抗剂，YM-90709抑制抗原诱导的嗜酸性粒细胞招募进入气道，与抗IL-5 mAb的作用相同。YM-90709能够抑制IL-5与人嗜酸性粒细胞上的IL-5R的结合，但不抑制GM-CSF与GM-CSFR的结合。此外，YM-90709抑制了IL-5诱导的嗜酸性粒细胞存活和Janus激酶2的酪氨酸磷酸化，但对GM-CSF诱导的没有影响。[2]

YM-90709抑制布朗挪威大鼠抗原诱导的气道炎症。YM-90709是一种新型的IL-5R拮抗剂，具有抗IL-5 mAb对抗原诱导的嗜酸性粒细胞浸润到常用于抗体估计的BDF1小鼠气道的效果。[2]这是首次报道YM-90709作为新型IL-5R拮抗剂对抗原诱导的嗜酸性粒细胞和其他白细胞浸润到布朗挪威（BN）大鼠BALF中的体内效应的研究。[3]

Nuclease assay: Reactions with oligonucleotide nonhairpin substrates contains 25 mM MOPS (pH 7.0), 60 mM KCl, 0.2% Tween 20, 2 mM DTT, 1 mM or 5 MnCl2 (or 5 mM MgCl2, or 5 mM CaCl2), 0.1 pmol of DNA substrate, and 0.3 pmol of Mre11 (or an equivalent amount of Mre11 complexed with Rad50) in a volume of 10 μl, and are incubated at 37°C for 30 min. SDS, EDTA, and proteinase K are then added to final concentrations of 0.2%, 5 mM, and 0.1 mg/ml, respectively, and incubated for another 15 min. 4 μl of each reaction is mixed with 4 μl of formamide loading buffer, and then loaded onto a sequencing gel containing 10% acrylamide and 7 M urea. After the run, each gel is analyzed using a phosphorimaging system. Reactions containing hairpin substrates are identical to those with nonhairpin substrates except that 3 pmol of Mre11 is added to reactions as indicated, and the reactions are incubated at room temperature overnight. Nonhomologous end-joining reactions contains 25 mM MOPS (pH 7.0), 60 mM KCl, 0.2% Tween 20, 2 mM DTT, 4 mM MgCl2, 2 mM MnCl2, 0.5 mM ATP, 4 ng of plasmid DNA, 10% polyethylene glycol, 0.01 pmol of human DNA ligase I, and 0.06 pmol of Mre11 or 0.1 units of E. coli exonuclease III (GIBCO-BRL), in a volume of 10 μl. After incubation at 37°C for 25 min, Tween 20 is added to a final concentration of 0.5%, and a 2.5 μl aliquot is amplified by PCR using primers DAR5 and DAR147. PCR products are cloned using the TA cloning kit and sequenced using an automated ABI Capillary Genetic Analyzer.