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Chemical Compound Review:

Brd-MP [(2R,3S,4R,5R)-5-(4- aminocarbonyl-5...

Synonyms: AC1L3ZBD, AC1Q6RVW, AR-1C3521, Mizoribine monophosphate, Bredinin 5'-monophosphate

Koyama, H. et al., Horie, T. et al., Mizushina, Y. et al.

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High impact information on Brd-MP

These results support the mechanism of bredinin cytotoxicity, that Brd-MP formed in sensitive cells exposed to the antibiotic blocks the conversion of IMP to XMP by inhibiting IMP dehydrogenase [1].
These results demonstrate that the bredinin resistance is attributed to a defective AK activity and, therefore, that bredinin is metabolized by AK, which may phosphorylate it to a toxic nucleotide, bredinin 5'-monophosphate (Brd-MP), in sensitive cells [1].
We found that bredinin-5'-monophosphate (breMP) could be a potent inhibitor of mammalian DNA polymerase alpha(pol.alpha) and (pol.beta) in vitro, although bredinin itself has no such effects [2].
The biochemical inhibition mode of bredinin-5'-monophosphate on DNA polymerase beta [3].

References

Genetic and biochemical studies on the activation and cytotoxic mechanism of bredinin, a potent inhibitor of purine biosynthesis in mammalian cells. Koyama, H., Tsuji, M. Biochem. Pharmacol. (1983) [Pubmed]
A 5'-monophosphate form of bredinin selectively inhibits the activities of mammalian DNA polymerases in vitro. Horie, T., Mizushina, Y., Takemura, M., Sugawara, F., Matsukage, A., Yoshida, S., Sakaguchi, K. Int. J. Mol. Med. (1998) [Pubmed]
The biochemical inhibition mode of bredinin-5'-monophosphate on DNA polymerase beta. Mizushina, Y., Matsukage, A., Sakaguchi, K. Biochim. Biophys. Acta (1998) [Pubmed]

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