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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Favipiravir (T-705) is a potent and selective RNA-dependent RNA polymerase inhibitor, used to treat influenza virus infections.
Vidarabine is an antiviral drug by interfering with the synthesis of viral DNA, used to treat herpes simplex and varicella zoster viruses.
Uridine is a nucleoside, contains a uracil attached to a ribose ring via a β-N1-glycosidic bond.
Rifampin is a DNA-dependent RNA polymerase inhibitor, used to treat a number of bacterial infections.
Mitomycin C is an antineoplastic antibiotic by inhibiting DNA synthesis, used to treat different cancers.
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