Adherex Technologies, Inc.

Mcgill University

Adherex Inc.

Barbara J Gour

Orest W Blaschuk

James Matthew Symonds

Stephen Byers

Riaz Farookhi

Anmar Ali

Patrick Doherty

Feng Ni

Zhigang Chen

Stephanie Denise Michaud

Zenjian Hu

Shaomeng Wang

J Steven Alexander

Shoameng Wang

Compositions and methods for modulating OB-cadherin-mediated functions are provided. The compositions and methods employ OB-cadherin modulating agents which generally comprise one or more of: (a) a peptide sequence that is at least 50% identical to an OB-cadherin CAR sequence; (b) a non-peptide mimetic of an OB-cadherin CAR sequence; (c) a substance, such as an antibody or antigen-binding fragment thereof, that specifically binds an OB-cadherin CAR sequence; and/or (d) a polynucleotide encoding a polypeptide that comprises an OB-cadherin CAR sequence or analogue thereof.

Compounds and methods for modulating OB-cadherin-mediated function

Peptidomimetics of cyclic peptides, and compositions comprising such peptidomimetics are provided. The peptidomimetics have a three-dimensional structure that is substantially similar to a three-dimensional structure of a cyclic peptide that comprises a cadherin cell adhesion recognition sequence HAV. Methods for using such peptidomimetics for modulating cadherin-mediated cell adhesion in a variety of contexts are also provided.

Peptidomimetic modulators of cell adhesion

Methods for using modulating agents to enhance or inhibit cadherin-mediated cell adhesion in a variety of in vivo and in vitro contexts are provided. In particular, the modulating agents may be used in the therapy of multiple sclerosis and other demyelinating diseases. The modulating agents comprise at least one cadherin cell adhesion recognition sequence (HAV) or an antibody or fragment thereof that specifically binds to a cadherin cell adhesion recognition sequence. Modulating agents may additionally comprise one or more cell adhesion recognition sequences recognized by other adhesion molecules. Such modulating agents may, but need not, be linked to a targeting agent, drug and/or support material.

Compounds and methods for regulating cell adhesion

Cyclic peptides and compositions comprising such cyclic peptides are provided. The cyclic peptides comprise a classical cadherin cell adhesion recognition sequence HAV. Methods for using such peptides and compositions for inducing apoptosis in cadherin-expressing cells, such as cancer cells, are also provided.

Compounds and methods for modulating apoptosis

Modulating agents for inhibiting an interaction between &#x3b1;-catenin and &#x3b2;-catenin are provided. The modulating agents comprise one or more of: (a) a &#x3b2;-catenin HAV motif; (b) a peptide analogue or mimetic of a &#x3b2;-catenin HAV motif; or (c) an antibody or antigen-binding fragment thereof that specifically binds to a &#x3b2;-catenin HAV motif. Methods for using such modulating agents for inhibiting cadherin-mediated cell adhesion in a variety of contexts are also provided.

Compounds and methods for inhibiting the interaction between &#x3b1;-catenin and &#x3b2;-catenin

Cyclic peptides comprising a cadherin cell adhesion recognition sequence HAV, and compositions comprising such cyclic peptides, are provided. Methods for using such peptides for modulating cadherin-mediated cell adhesion in a variety of contexts are also provided.

Compounds and methods for modulating cell adhesion

Modulating agents for inhibiting or enhancing nonclassical cadherin mediated cell adhesion are provided. The modulating agents comprise one or more of: (a) a peptide sequence that is at least 50% identical to a nonclassical cadherin CAR sequence; (b) a non-peptide mimetic of a nonclassical cadherin CAR sequence; (c) a substance, such as an antibody or antigen-binding fragment thereof, that specifically binds a nonclassical cadherin CAR sequence; and/or (d) a polynucleotide encoding a polypeptide that comprises a nonclassical cadherin CAR sequence or analogue thereof. Methods for using such modulating agents for modulating nonclassical cadherin-mediated cell adhesion in a variety of contexts are also provided.

Compounds and methods for modulating nonclassical cadherin-mediated functions

Cyclic peptides and compositions comprising such cyclic peptides are provided. The cyclic peptides comprise a cadherin cell adhesion recognition sequence HAV. Methods for using such peptides and compositions for modulating cadherin-mediated cell adhesion in a variety of contexts are also provided.

Methods for using modulating agents to enhance or inhibit claudin-mediated cell adhesion in a variety of in vivo and in vitro contexts are provided. Within certain embodiments, the modulating agents may be used to increase blood/brain barrier permeability. The modulating agents comprise at least one claudin cell adhesion recognition sequence or an antibody or fragment thereof that specifically binds the claudin cell adhesion recognition sequence. Modulating agents may additionally comprise one or more cell adhesion recognition sequences recognized by other adhesion molecules. Such modulating agents may, but need not, be linked to a targeting agent, drug and/or support material.

Compounds and methods for modulating claudin-mediated functions

Modulating agents and methods for enhancing or inhibiting cadherin-mediated functions are provided. The modulating agents comprise at least an HAV binding motif, an analogue or peptidomimetic thereof, or an antibody or fragment thereof that specifically binds to such a motif. Modulating agents may additionally comprise one or more cell adhesion recognition sequences recognized by cadherins and/or other adhesion molecules. Such modulating agents may, but need not, be linked to a targeting agent, drug and/or support material.

Compounds and methods for modulating adhesion molecule function

Methods for using modulating agents to enhance or inhibit occludin-mediated cell adhesion in a variety of in vivo and in vitro contexts are provided. Within certain embodiments, the modulating agents may be used for cancer therapy or to increase immune cell infiltration into tumors. The modulating agents comprise at least one occludin cell adhesion recognition sequence or an antibody or fragment thereof that specifically binds the occludin cell adhesion recognition sequence. Modulating agents may additionally comprise one or more cell adhesion recognition sequences recognized by the other adhesion molecules. Such modulating agents may, but need not, be linked to a targeting agent, drug and/or support material.

Compounds and methods for cancer therapy

Agents that inhibit the development of cancer and tumor growth are provided. Such agents comprise a classical cadherin CAR sequence HAV within a cyclic peptide ring, and may be used to prevent or treat cancer.

Method for using modulating agents to enhance or inhibit claudin-mediated cell adhesion in a variety of in vivo and in vitro contexts are provided. Within certain embodiments, the modulating agents may be used to increase blood/brain barrier permeability. The modulating agents comprise at least one claudin cell adhesion recognition sequence or an antibody or fragment thereof that specifically binds the claudin cell adhesion recognition sequence. Modulating agents may additionally comprise one or more cell adhesion recognition sequence recognized by other adhesion molecules. Such modulating agents may, but need not, be linked to a targeting agent, drug and/or support material.

Growing community of inventors

Kemptville, Canada

Barbara J Gour