Ibudilast (Synonyms: AV 411,KC-404)

IC50: 54-239 nM

Ibudilast is an inhibitor of PDE4.

Phosphodiesterases (PDEs) are critical inflammation and wound healing modulators. Specific targeting of PDEs for the treatment of various diseases, such as chronic obstructive pulmonary disease (COPD), has been investigated.

In vitro: Ibudilast could potently inhibit purified human PDE4A, 4B, 4C and 4D with IC50 values at 54, 65, 239 and 166 nM, respectively. Ibudilast was also able to effectively block LPS-induced tumor necrosis factor and N-formyl-MetLeu-Phe-induced leukotriene B4 biosynthesis in human whole blood [1].

In vivo: Rats received a daily oral administration of 10, 30 or 60 mg/kg ibudilast. Results showed that in the vehicle-treated animals, white matter lesions and microglial activation occurred in the optic tract, internal capsule and corpus callosum. A low dose of ibudilast failed to suppress the white matter lesions and microglial activation, whereas a dose of either 30 or 60 mg/kg ibudilast ameliorated these lesions [2].

Clinical trial: Ibudilast was studied in 13 asthmatics for its effect on airway hypersensitivity to histamine inhalation. The PC20 values improved significantly following the initial treatment with ibudilast. In addition, the severity of the attacks decreased significantly. Improvements in the PC20 and asthmatic symptoms also were observed in the disodium chromoglycate group, but these were equal to or lesser than those in the ibudilast group [3].

References:
[1] Huang, Z. ,Liu, S.,Zhang, L., et al. Preferential inhibition of human phosphodiesterase 4 by ibudilast. Life Sciences 78(23), 2663-2668 (2006).
[2] Wakita H, Tomimoto H, Akiguchi I, Lin JX, Ihara M, Ohtani R, Shibata M.  Ibudilast, a phosphodiesterase inhibitor, protects against white matter damage under chronic cerebral hypoperfusion in the rat. Brain Res. 2003 Nov 28;992(1):53-9.
[3] Kawasaki A, Hoshino K, Osaki R, Mizushima Y, Yano S.  Effect of ibudilast: a novel antiasthmatic agent, on airway hypersensitivity in bronchial asthma. J Asthma. 1992;29(4):245-52.