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Mimosine


ACCESSION NB: DB01055 (APRD00647)


TYPE: small molecule


GROUP: approved


DESCRIPTION:
3-Hydroxy-4-oxo-1(4H)-pyridinealanine. An antineoplastic alanine-substituted pyridine derivative isolated from Leucena glauca. [PubChem]

CATEGORIES:
Antineoplastic Agents

PHARMACODYNAMICS:
Mimosine inhibits DNA synthesis at the level of elongation of nascent chains by altering deoxyribonucleotide metabolism. It arrests the cell cycle in the late G(1) phase.

MECHANISM OF ACTION:
Mimosine causes inhibition of DNA replication, changes in the progression of the cells in the cell cycle, and apoptosis. Mimosine appears to introduce breaks into DNA. Mimosine is an iron/zinc chelator. Iron depletion induces DNA double-strand breaks in treated cells, and activates a DNA damage response that results in focal phosphorylation of histones. This leads to inhibition of DNA replication and/or DNA elongation. Some studies indicate that mimosine prevents the initiation of DNA replication, whereas other studies indicate that mimosine disrupts elongation of the replication fork by impairing deoxyribonucleotide synthesis by inhibiting the activity of the iron-dependent enzyme ribonucleotide reductase and the transcription of the cytoplasmic serine hydroxymethyltransferase gene (SHMT). Inhibition of serine hydroxymethyltransferase is moderated by a zinc responsive unit located in front of the SHMT gene.

PROTEIN BINDING:
>99.5%

AFECTED ORGANISMS:
Humans and other mammals