公开(公告)号：US11319344B2

公开(公告)日：2022-05-03

申请号：US15550766

申请日：2016-02-15

Applicant: AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH

Inventor： Yaw Sing Tan ,  Christopher John Brown ,  Chandra S. Verma ,  Fernando Jose Ferrer Gago ,  David P. Lane ,  Thomas Joseph

IPC: A61K38/08 ,  A61K38/10 ,  C07K7/06 ,  C07K7/08 ,  A61K45/06 ,  A61P35/00 ,  A61K38/00

Abstract: The present invention relates to non-membrane disruptive and p53 activating stapled peptides, as well as methods of treatment of cancer involving the use of these peptides. In one embodiment, the peptide comprises or consist of the amino acid sequence of TSFXaa1EY-WXaa3LLXaa2, where Xaa1 is (R)-2-(7′-octenyl)alanine or derivative thereof, or is (R)-2-(4′-pentenyl)alanine or derivative thereof; and Xaa2 and Xaa3 are independently any type of amino acid or modified amino acid. In another embodiment, the peptide comprising or consisting of the amino acid sequence of TSFXaa1EYW Xaa3LLXaa2ENXaa5, wherein Xaa1 and Xaa3 are any type of amino acid or modified amino acid; Xaa2 is S, or P, or (S)-2-(4′-pentenyl)alanine or a derivative of (S)-2-(4′-pentenyl)alanine; and wherein Xaa5 is F or Y.

公开(公告)号：US20220267376A1

公开(公告)日：2022-08-25

申请号：US17618751

申请日：2020-06-16

Applicant: Tomi K. SAWYER ,  Pietro ARONICA ,  Christopher J. BROWN ,  Fernando J. FERRER ,  Charles W. JOHANNES ,  Srinivasaraghavan KANNAN ,  David P. LANE ,  Anthony W. PARTRIDGE ,  Yaw Sing TAN ,  Chandra S. VERMA ,  Tsz Ying YUEN ,  Merck Sharp & Dohme Corp. ,  Agency for Science, Technology and Research ,  MSD International GMBH (Singapore Branch)

Inventor： Pietro 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

IPC: C07K7/08 ,  A61K45/06 ,  C07K7/06 ,  A61P35/00

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.