PR-104A is a corresponding alcohol that is systemically converted from PR-104 and a hypoxia-targeted anticancer agent with IC50 of 153 and 60 μM for wild-type CHO AA8 under aerobic and anoxic conditions. PR-104A itself showed modest but significant selectivity for anoxic cells. In a study, the estimated unbound human clearance of PR-104A was 211 L/h/70 kg, with a steady state unbound volume of 105 L/70 kg. The size equivalent unbound PR-104A clearance was 2.5 times faster in dogs, 0.78 times slower in rats and 0.63 times slower in mice, which may reflect reported species differences in PR-104A O-glucuronidation. PR-104A is glucuronidated by UGT2B7 with high specificity and appears to make a major contribution to clearance of PR-104A in humans.
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
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Madrasin is a potent and cell penetrant splicing inhibitor that interferes with the early stages of spliceosome assembly.
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