Aileron Therapeutics, Inc.

Medarex Inc.

E. R. Squibb Sons, Inc.

Vincent Guerlavais

Haichun Huang

Noriyuki Kawahata

Eric Feyfant

Sanjeev Gangwar

Huw M Nash

Carl Elkin

Liang Chen

Tomi K Sawyer

Bradford Graves

Zhi-Hong Li

Manoj Samant

Qian Zhang

Sharon Elaine Boyd

Nils Lonberg

Josephine M Cardarelli

David B Passmore

Chin Pan

Bilal Sufi

David Allen Annis

Scott Paul Lentini

Christopher R Conlee

Karen Olson

Manuel Aivado

Kilian Horgan

Killian Horgan

Bradford J Graves

Sharon Boyd

Sanjeev Ganwar

David John King

The present disclosure describes the synthesis of peptidomimetic macrocycles and methods of using peptidomimetic macrocycles to treat a condition. The present disclosure also describes methods of using peptidomimetic macrocycles in combination with at least one additional pharmaceutically-active agent for the treatment of a condition, for example, cancer.

Peptidomimetic macrocycles and uses thereof

The present invention provides novel peptidomimetic macrocycles and methods of using such macrocycles for the treatment of disease.

Peptidomimetic macrocycles

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.

The present invention provides peptidomimetic macrocycles capable of modulating growth hormone levels and methods of using such macrocycles for the treatment of disease.

The present invention provides peptidomimetic macrocycles capable of regulating HIF1&#x3b1; and methods of using such macrocycles for the treatment of diseases.

Peptidomimetic macrocycles and use thereof in regulating HIF1alpha

Provided herein are peptidomimetic macrocycles and methods of using such macrocycles for the treatment of disease.

Triazole-crosslinked and thioether-crosslinked peptidomimetic macrocycles

The present invention provides novel peptidomimetic macrocycles and methods of using such macrocycles for the treatment of viral disease.

The disclosed peptidomimetic macrocycles modulate the activity of MCL-1. Myeloid cell leukemia 1 (MCL-1) is a protein that inhibits cell death. Peptidomimetic macrocycles, pharmaceutical compositions, and methods disclosed herein can be used for the treatment of disease in which MCL-1 is over-expressed, such as cancer. In particular, MCL-1-modulating peptidomimetic macrocycles disclosed herein can be applied in the setting of resistance to BCL-2 family inhibitors, which is often engendered by MCL-1 over-expression or hyper-activation.

Peptidomimetic macrocycles as modulators of MCL-1

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Arlington, MA, United States of America

Vincent Guerlavais