Revolution Medicines, Inc.

Warp Drive Bio, Inc.

Dylan Talbot Stiles

Gregory Lawrence Verdine

Sharon Ann Townson

Uddhav Kumar Shigdel

Neville J Anthony

Brian Roger Bowman

Mathew Edward Sowa

Jay Paul Morgenstern

Seung-Joo Lee

Keith Earl Robison

Joshua Alan Van Dyke Blodgett

M James Nichols

Matthew James Nichols

The invention features compounds (e.g., macrocyclic compounds) capable of modulating biological processes, for example through binding to a presenter protein (e.g., a member of the FKBP family, a member of the cyclophilin family, or PIN1) and a target protein such as CEP250. These compounds bind endogenous intracellular presenter proteins, such as the FKBPs or cyclophilins, and the resulting binary complexes selectively bind and modulate the activity of the target protein. Formation of a tripartite complex among the presenter protein, the compound, and the target protein is driven by both protein-compound and protein-protein interactions, and both are required for modulation of target protein activity.

Compounds that participate in cooperative binding and uses thereof

The invention features compounds (e.g., macrocyclic compounds) capable of modulating biological processes, for ex ample through binding to a presenter protein (e.g., a member of the FKBP family, a member of the cyclophilin family, or PIN1) and a target protein such as CEP250. These compounds bind endogenous intracellular presenter proteins, such as the FKBPs or cyclophilins, and the resulting binary complexes selectively bind and modulate the activity of the target protein. Formation of a tripartite complex among the presenter protein, the compound, and the target protein is driven by both protein-compound and protein-protein interactions, and both are required for modulation of target protein activity.

The present disclosure provides methods and reagents useful for analyzing protein-protein interfaces such as interfaces between a presenter protein (e.g., a member of the FKBP family, a member of the cyclophilin family, or PIN1) and a target protein. In some embodiments, the target and/or presenter proteins are intracellular proteins. In some embodiments, the target and/or presenter proteins are mammalian proteins.

Methods and reagents for analyzing protein-protein interfaces

The invention relates to macrocyclic compounds capable of modulating biological processes through binding to a presenter protein and a target protein. These compounds bind endogenous intracellular presenter proteins, such as the FKBPs or cyclophilins, and the resulting binary complexes selectively bind and modulate the activity of intracellular target proteins. Formation of a tripartite complex among the presenter protein, the compound, and the target protein is driven by both protein-compound and protein-protein interactions, and both are required for modulation of the targeted protein's activity. In some embodiment, the compounds of the invention 're-program' the binding of the presenter proteins to protein targets that either do not normally bind to the presenter protein.

Growing community of inventors

Chestnut Hill, MA, United States of America

Dylan Talbot Stiles