| Description | Bunaprolast (U66858) is a novel and potent leukotriene B4 (LTB4) inhibitor.Bunaprolast exhibits oxidative degradation activity and inhibits lipoxygenase and TXB2 release. |
| In vitro | Bunaprolast (U-66,858) undergoes deacetylation to an initial metabolite with similar pharmacological potency. The inhibitory effects of the semi-quinone Bunaprolast and its metabolite U-68,244 on the ionophore-induced formation of leukotriene B4 (LTB4) are examined in human whole blood (WB). Preincubation of Bunaprolast and U-68,244 for 1 min prior to the challenge of blood with calcium ionophore A23187 results in IC50s of 1080±644 and 820±442 nM, respectively. After 60 min preincubation, IC50s are 250±85 and 270±79 nM. The activity of the lipoxygenase inhibitor AA-861 in this system is similar to that of Bunaprolast, while vitamin K and the sulfate conjugate of Bunaprolast show significant inhibition of LTB4 release only at micromolar concentrations. Bunaprolast exhibits significant inhibition of thromboxane A2 release (p<0.02) in a comparative study with the known cyclooxygenase (CO) inhibitor Flurbiprofen[2]. |
| In vivo | The IgE-mediated hypersensitivity to Ascaris antigen in reactor rhesus primates is used to assess the pharmacologic profile of Bunaprolast (U-66,858). When given orally, Bunaprolast shows dose-related inhibition of resistance (RL) and compliance (Cdyn) changes. When administered via aerosol, it exhibits dose-independent inhibition. In 15 animals receiving aerosols (52±32 to 53±10% for RL, p=0.05, and 45±19 to 28±19% Cdyn inhibitions, p=0.05) at concentrations ranging from 5.0% to 0.1%, Bunaprolast demonstrates significant effects. By the oral route, inhibition is observed at 1-4 h following administration. In 5 animals, oral doses of 10 and 5 mg/kg result in inhibition (RL by 98±2 to 78±1.5%, p=0.01, and Cdyn by 75±17 to 60.9±9.1%, p=0.05) for 10 and 5 mg/kg of Bunaprolast, respectively[1]. |
| Target activity | LTB4:250±85 nM |
| Synonyms | U66858 |
| molecular weight | 272.34 |
| Molecular formula | C17H20O3 |
| CAS | 99107-52-5 |
| Storage | store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| References | 1. Johnson HG, et al. Activity of a novel hydroquinone inhibitor of leukotriene synthesis (U-66,858) in the rhesus monkey Ascaris reactor. Int Arch Allergy Appl Immunol. 1988;87(2):204-7. 2. Summers JA, et al. Lipoxygenase inhibitory activity of U-66,858 and its deacetylated metabolite U-68,244 in human whole blood. Agents Actions. 1994 Mar;41(1-2):32-6. |