US 2026/0308203 A1 · P53 ACTIVATOR PEPTIDOMIMETIC MACROCYCLES

P53 activator peptidomimetic macrocycles

AssigneesMerck Sharp & Dohme Corp., Agency for Science, Technology and Research, MSD International GMBH (Singapore Branch)

InventorsPietro Aronica, Christopher J. Brown, Fernando J. Ferrer, Charles W. Johannes, Srinivasaraghavan Kannan, David P. Lane, Anthony W. Partridge, Tomi K. Sawyer, Yaw Sing Tan, Chandra S. Verma, Tsz Ying Yuen

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Abstract

Peptidomimetic macrocycles that comprise all-D configuration α-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.

Claims20

Dependent claims

A peptidomimetic macrocycle comprising:

a peptide of D configuration α-amino acids having the amino acid sequence set forth in SEQ ID NO:
16 and two staples or one stitch, wherein each staple comprises a hydrocarbon crosslinker linking the α-carbons of two α,α-disubstituted amino acids separated by at least two α-amino acids and each stitch comprises two hydrocarbon crosslinkers linking the α-carbons of two α,α-disubstituted amino acids to the α-carbon of a common α,α-disubstituted amino acid situated between the two α,α-disubstituted amino acids.

Dependencies are inferred from the claim text.

Facts

Application

19/702,235Filed 9 Jun 2026

Priority

21 Jun 2019

Published

8 Oct 2026

Term ends

Not estimatedThe source records don’t support an estimate.

Classification8 codes

C07K 7/08
Linear peptides containing only normal peptide links: having 12 to 20 amino acids
A61K 45/06
Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00: mixtures of active ingredients without…
A61P 35/00
Antineoplastic agents
C07K 7/06
Linear peptides containing only normal peptide links: having 5 to 11 amino acids