P53 ACTIVATOR PEPTIDOMIMETIC MACROCYCLES
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United States of America Patent
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Issued Date -
Aug 25, 2022
app pub date -
Jun 16, 2020
filing date -
Jun 21, 2019
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Abstract
Peptidomimetic macrocycles that comprise all-D configuration ?-amino acids and bind mouse double minute 2 (MDM2 aka E3 ubiquitin-protein ligase) and MDMX (aka MDM4) are described. These all-D configuration α-amino acid peptidomimetic macrocycles are protease resistant, cell permeable without inducing membrane disruption, and intracellularly activate p53 by binding MDM2 and MDMX thereby antagonizing MDM2 and MDMX binding to p53. These peptidomimetic macrocycles may be useful in anticancer therapies, particularly in combination with chemotherapy or radiation therapy.
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