YM-976

YM-976 is a phosphodiesterase 4 (PDE4) inhibitor (IC₅₀ = 2.2 nM for the human peripheral leukocyte enzyme).¹ It is selective for PDE4 over PDE1, -2, -3, and -5 (IC₅₀s = >3 µM for all). YM-976 inhibits LPS-induced TNF-α production in human peripheral blood mononuclear cells (PBMCs). In vivo, YM-976 inhibits carrageenan-induced pleural cavity cell infiltration in a rat model of pleurisy (ED₃₀ = 9.1 mg/kg). It inhibits antigen-induced lung eosinophil infiltration in rats, mice, and ferrets (ED₅₀s = 1.7, 5.8, and 1.2 mg/kg, respectively) and does not induce emesis in ferrets when administered at doses up to 10 mg/kg.² YM-976 reduces ovalbumin-induced bronchoconstriction, as well as airway plasma leakage, eosinophil infiltration, and hyperreactivity in a guinea pig model of asthma (ED₅₀s = 7.3, 5.7, 1, and 0.52 mg/kg, respectively).³ It also reduces citric acid-induced cough in guinea pigs.⁴

WARNING This product is not for human or veterinary use.

1. Aoki, M., Kobayashi, M., Ishikawa, J., et al. A novel phosphodiesterase type 4 inhibitor, YM976 (4-(3-chlorophenyl)-1,7-diethylpyrido[2,3-d]pyrimidin-2(1H)-one), with little emetogenic activity. J. Pharmacol. Exp. Ther. 295(1), 255-260 (2000).

2. Aoki, M., Fukunaga, M., Kitagawa, M., et al. Effect of a novel anti-inflammatory compound, YM976, on antigen-induced eosinophil infiltration into the lungs in rats, mice, and ferrets. J. Pharmacol. Exp. Ther. 295(3), 1149-1155 (2000).

3. Aoki, M., Yamamoto, S., Kobayashi, M., et al. Antiasthmatic effect of YM976, a novel PDE4 inhibitor, in guinea pigs. J. Pharmacol. Exp. Ther. 297(1), 165-173 (2001).

4. Mokrý, J., Urbanová, A., Medvedová, I., et al. Effects of selective inhibition of PDE4 by YM976 on airway reactivity and cough in ovalbumin-sensitized guinea pigs. Adv. Exp. Med. Biol. 921, 61-70 (2016).