Massachusetts Institute of Technology

Dana-Farber-Cancer Institute Inc.

Yivan Jiang

Jeremiah Allen Johnson

Hung Vanthanh Nguyen

Farrukh Vohidov

Nolan Gallagher

Yoshiki Shibuya

Irene M Ghobrial

Jonathan Christopher Barnes

Deborah June Choi Ehrlich

Angela Xiaodi Gao

Alexandre Detappe

Michael Agius

XueZhou Wang

The present disclosure provides, in some aspects, macromonomers of Formula (I), and salts thereof; methods of preparing the macromonomers, and salts thereof; Brush prodrugs (polymers); methods of preparing the Brush prodrugs; compounds of Formula (II); conjugates of Formula (III), and salts thereof; pharmaceutical compositions comprising a Brush prodrug, or a conjugate or a salt thereof; kits comprising: a macromonomer or a salt thereof, a Brush prodrug, a compound, a conjugate or a salt thereof, or a pharmaceutical composition; methods of using the Brush prodrugs, or conjugates or salts thereof; and uses of the Brush prodrugs, and conjugates or salts thereof. These chemical entities may be useful in delivering pharmaceutical agents to a subject or cell.

Brush prodrugs and uses thereof

Disclosed are methods, compositions, reagents, systems, and kits to prepare and utilize branched multi-functional macromonomers, which contain a ring-opening metathesis polymerizable norbornene group, one or more reactive sites capable of undergoing click chemistry, and a terminal acyl group capable of undergoing a coupling reaction; branched multi-cargo macromonomers; and the corresponding polymers are disclosed herein. Various embodiments show that the macromonomers and polymers disclosed herein display unprecedented control of cargo loading of agents. These materials have the potential to be utilized for the treatment of diseases and conditions such as cancer and hypertension.

Branched multi-functional macromonomers and related polymers and uses thereof

Disclosed multifunctional compounds, conjugates, macromolecules, and polymers that target dysregulated proteins for degradation. Also disclosed are methods of preparation, compositions, kits, and methods of use relating to the degraders.

Proteolysis targeting chimeric molecules (PROTACs) with functional handles and uses thereof

Macromolecules comprising triazoles and related compositions and methods are provided. In some embodiments, a macromolecule may comprise one or more repeat units including a triazole and a functionalizable pendant group. The macromolecule may also comprise one or more orthogonally addressable end groups. In some embodiments, one or more repeat units may be formed by a synthetic process that allows for precise control over stereochemistry, pendant functionality, and/or the spatial relationship (e.g., distance) between groups in the repeat unit(s). Such precise control over pendant group and repeat unit structure allows for the macromolecule functionality, stereochemistry, and spacing between groups (e.g., pendant groups) to be precisely controlled. Macromolecules described herein may be used for a wide variety of applications, including the delivery of active agents.

Macromolecules comprising triazoles and related compounds

Macromolecules comprising triazoles

Branched multi-functional macromonomers and uses thereof

In some embodiments, macromolecules and related methods are provided. In some embodiments, an iterative growth process may be used to form a macromolecule comprising one or more repeat units comprising a functionalizable pendant group, with precise control over mass, length, backbone sequence, pendant group sequence, and/or stereochemistry, amongst other features. Macromolecules (e.g., non-natural macromolecules) form from the iterative growth process, described herein, may be used for a wide variety of applications, including the delivery of active agents.

Formation of macromolecules using iterative growth and related compounds

Growing community of inventors

Revere, MA, United States of America

Yivan Jiang