Peptidomimetic macrocycles
First Claim
1. A method for treating a cancer, comprising administering to a subject with the cancer a therapeutically effective amount of a pharmaceutical product comprising:
- (a) a first therapeutic agent comprising an inhibitor of an interaction between p53 and MDM2 and/or an inhibitor of an interaction between p53 and MDMX, and(b) a second therapeutic agent comprising a chemotherapeutic agent;
wherein the first therapeutic agent is a peptidomimetic macrocycle comprising an amino acid sequence with at least about 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ IP NOs;
10-457, or pharmaceutically acceptable salt thereof; and
wherein the peptidomimetic macrocycle has a Formula;
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Accused Products
Abstract
Provided herein are peptidomimetic macrocycles containing amino acid sequences with at least two modified amino acids that form an intramolecular cross-link that can help to stabilize a secondary structure of the amino acid sequence. Suitable sequences for stabilization include those with homology to the p53 protein. These sequences can bind to the MDM2 and/or MDMX proteins. Also provided herein are methods of using such macrocycles for the treatment of diseases and disorders, such as cancers or other disorders characterized by a low level or low activity of a p53 protein or high level of activity of a MDM2 and/or MDMX protein.
596 Citations
21 Claims
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1. A method for treating a cancer, comprising administering to a subject with the cancer a therapeutically effective amount of a pharmaceutical product comprising:
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(a) a first therapeutic agent comprising an inhibitor of an interaction between p53 and MDM2 and/or an inhibitor of an interaction between p53 and MDMX, and (b) a second therapeutic agent comprising a chemotherapeutic agent; wherein the first therapeutic agent is a peptidomimetic macrocycle comprising an amino acid sequence with at least about 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ IP NOs;
10-457, or pharmaceutically acceptable salt thereof; and
wherein the peptidomimetic macrocycle has a Formula; - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21)
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Specification