Abstract: Methods and compositions using E-selectin antagonists are provided for the treatment and prevention of diseases and disorders treatable by inhibiting binding of E-selectin to an E-selectin ligand. Described herein are E-selectin antagonists including, for example, glycomimetic compounds, antibodies, aptamers and peptides that are useful in methods for treatment of cancers, and treatment and prevention of metastasis, inhibiting infiltration of the cancer cells into bone marrow, reducing or inhibiting adhesion of the cancer cells to endothelial cells including cells in bone marrow, and inhibiting thrombus formation.
Type:
Application
Filed:
April 20, 2022
Publication date:
March 30, 2023
Applicant:
GLYCOMIMETICS, INC.
Inventors:
John L. MAGNANI, Arun K. SARKAR, Myung-Gi BAEK, Frank E. ANDERSON, III, Yanhong LI
Abstract: Compounds, compositions, and methods for treatment and/or prevention of at least one disease, disorder, and/or condition by inhibiting binding of galectin-3 to ligands are disclosed. For example, inhibitors of galectin-3 are described and pharmaceutical compositions comprising at least one such agent are described.
Type:
Application
Filed:
December 23, 2020
Publication date:
March 23, 2023
Applicant:
GLYCOMIMETICS, INC.
Inventors:
John L. MAGNANI, John M. PETERSON, Yusuf U. VOHRA, lndranath GHOSH, Jason NOGUEIRA, Arun K. SARKAR, Debatosh MAJUMDAR
Abstract: Compounds, compositions, and methods for treating and/or preventing at least one disease, disorder, and/or condition N associated with E-selectin, galectin-3, and/or CXCR4 chemokine receptor activity are disclosed herein. For example, multimeric glycomimetic inhibitors of E-selectins, galectin-3, and/or CXCR4 chemokine receptors and their use for treating and/or preventing inflammatory diseases, fibrosis, and cancers are disclosed. Formula (I).
Type:
Application
Filed:
April 21, 2020
Publication date:
March 16, 2023
Applicant:
GLYCOMIMETICS, INC.
Inventors:
John L. MAGNANI, John M. PETERSON, Arun K. SARKAR, Yusufbhai U. VOHRA, Myung-Gi BAEK, Hong-Woon YANG
Abstract: Compounds, compositions, and methods for treatment and/or prevention of at least one disease, disorder, and/or condition by inhibiting binding of an E-selectin, galectin-3, or E-selectin and galectin-3 to ligands a disclosed. For example, heterobifunctional inhibitors of E-selectin and galectin-3 are described and pharmaceutical compositions comprising at least one such agent is described.
Type:
Grant
Filed:
December 28, 2018
Date of Patent:
January 10, 2023
Assignee:
GlycoMimetics, Inc.
Inventors:
John L. Magnani, John M. Peterson, Arun K. Sarkar, Yusufbhai U. Vohra, Hong-Woon Yang
Abstract: A process is provided for the synthesis of an intermediate of Formula 15 which is useful in the synthesis of E-selectin inhibitors. Also provided are useful intermediates obtained from the process.
Type:
Application
Filed:
August 18, 2020
Publication date:
September 15, 2022
Applicant:
GLYCOMIMETICS, INC.
Inventors:
Henry H. Flanner, John M. Peterson, Arun K. Sarkar, John L. Magnani, Gerd Osswald, Daniel Schwizer, Marc Lanz, Andreas Helmut Bernd Kyas
Abstract: Compositions and methods for the treatment of diseases, disorders, and/or conditions associated with the increased regulatory T lymphocyte cell function, comprising the administration of T-cell checkpoint inhibitors in combination with E-selectin inhibitors, C—X—C Motif Chemokine Receptor 4 (CXCR4) receptor inhibitors, and/or heterobifunctional inhibitors that comprise at least one E-selectin inhibitor linked to at least one CXCR4 receptor inhibitor, are disclosed.
Abstract: Cancer patients that express high levels of the E-selectin ligand (sialyl Lea/x) on their tumors have a poorer outcome. Interestingly, relapsed/refractory acute myeloid leukemia (AML) patients expressing high levels of sialyl Lex on their blasts show the greatest therapeutic response when treated with the E-selection inhibitor compound of Formula I. Transcriptome profiling of E-selectin ligand-forming glycosylation genes showed that ST3GAL4 and FUT7 were consistently expressed in the majority of cancers evaluated. Poor survival outcomes of FLT3-mutated AML patients that express high levels of ST3GAL4 and FUT7 implicated E-selectin in this disease state. These genes may be predictive biomarkers in AML patients. Methods of treatment of cancer comprising screening AML patients for expression of genes that contribute to the synthesis of the E-selectin ligand sialyl Lex, then treating those patients with an E-selection inhibitor, are disclosed.
Type:
Application
Filed:
July 12, 2020
Publication date:
August 25, 2022
Applicant:
GLYCOMIMETICS, INC.
Inventors:
John L. MAGNANI, William E. FOGLER, Helen M. THACKRAY, Eric J. FELDMAN, David STEWART
Abstract: Hematopoietic stem cell (HSC) transplantation is a promising treatment for patients with various hematological diseases, immunodeficiency, autoimmune disorders, and other genetic disorders. Considerable work continues to strive toward the identification of critical factors involved in the successful engraftment and reconstitution of HSC recipients. The identification of these critical components and the understanding of how they may be therapeutically targeted would result in improved patient survival. E-selectin inhibitors for use in increasing survival of individuals that receive HSC transplantation or for reconstitution of depleted and compromised bone marrow are disclosed.
Abstract: Methods for the treatment of sickle cell disease or complications associated therewith, including, for example, vaso-occlusive crisis, by the use of at least one E-selectin inhibitor and compositions comprising the same are disclosed.
Abstract: Compounds, compositions, and methods for modulating in vitro and in vivo processes mediated by selectin binding are described herein. For example, multimeric selectin modulators and their use are described, wherein the multimeric selectin modulators comprise a glycomimetic linked to a member of a class of compounds termed BASAs (Benzyl Amino Sulfonic Acids) or a member of a class of compounds termed BACAs (Benzyl Amino Carboxylic Acids).
Abstract: Compounds, compositions, and methods for treatment and/or prevention of at least one disease, disorder, and/or condition by inhibiting binding of an E-selectin to an E-selectin ligand are disclosed. For example, E-selectin antagonists are described and pharmaceutical compositions comprising at least one of the same.
Type:
Application
Filed:
November 9, 2021
Publication date:
June 9, 2022
Applicant:
GLYCOMIMETICS, INC.
Inventors:
John L. MAGNANI, John M. PETERSON, Arun K. SARKAR, Yusuf U. VOHRA, Myung-Gi BAEK
Abstract: Methods and compositions using E-selectin antagonists are provided for the treatment and prevention of diseases and disorders treatable by inhibiting binding of E-selectin to an E-selectin ligand. Described herein are E-selectin antagonists including, for example, glycomimetic compounds, antibodies, aptamers and peptides that are useful in methods for treatment of cancers, and treatment and prevention of metastasis, inhibiting infiltration of the cancer cells into bone marrow, reducing or inhibiting adhesion of the cancer cells to endothelial cells including cells in bone marrow, and inhibiting thrombus formation.
Type:
Grant
Filed:
August 17, 2020
Date of Patent:
May 17, 2022
Assignee:
GLYCOMIMETICS, INC.
Inventors:
John L. Magnani, Arun K. Sarkar, Myung-Gi Baek, Frank E. Anderson, III, Yanhong Li
Abstract: New methods for treating and/or preventing cardiovascular disease including, for example, myocardial infarction and atherosclerosis, by the use of at least one E-selectin inhibitor and compositions comprising the same are disclosed.
Type:
Grant
Filed:
March 1, 2017
Date of Patent:
April 5, 2022
Assignees:
GLYCOMIMETICS, INC, THE GENERAL HOSPITAL CORPORATION
Abstract: Compounds, compositions, and methods for treatment and/or prevention of at least one disease, disorder, and/or condition by inhibiting binding of an E-selectin, galectin-3, or E-selectin and galectin-3 to ligands are disclosed. For example, heterobifunctional inhibitors of E-selectin and galectin-3 are described and pharmaceutical compositions comprising at least one such agent is described.
Type:
Application
Filed:
December 26, 2019
Publication date:
March 24, 2022
Applicant:
GLYCOMIMETICS, INC.
Inventors:
John L. MAGNANI, John M. PETERSON, Arun K. SARKAR, Yusufbhai U. VOHRA, Indranath GHOSH, Jason NOGUEIRA
Abstract: Compounds, compositions, and methods for treatment and/or prevention of at least one disease, disorder, and/or condition by inhibiting binding of galectin-3 to ligands are disclosed. For example, inhibitors of galectin-3 are described and pharmaceutical compositions comprising at least one such agent is described.
Type:
Application
Filed:
December 26, 2019
Publication date:
March 10, 2022
Applicant:
GLYCOMIMETICS, INC.
Inventors:
John L. MAGNANI, John M. PETERSON, Arun K. SARKAR, Yusufbhai U. VOHRA, Indranath GHOSH, Jason NOGUEIRA
Abstract: Compounds, compositions, and methods for treatment and/or prevention of at least one disease, disorder, and/or condition by inhibiting binding of an E-selectin to an E-selectin ligand are disclosed. For example, E-selectin antagonists are described and pharmaceutical compositions comprising at least one of the same.
Type:
Grant
Filed:
March 12, 2018
Date of Patent:
December 14, 2021
Assignee:
GLYCOMIMETICS. INC.
Inventors:
John L Magnani, John M Peterson, Arun K Sarkar, Yusuf U Vohra, Myung-Gi Baek
Abstract: Compounds, compositions, and methods for treatment and/or prevention of at least one disease, disorder, and/or condition by inhibiting binding of an E-selectin to an E-selectin ligand are disclosed. For example, highly potent multimeric E-selectin antagonist are dessorbed and pharmaceutical compositions comprising at least one of the same.
Type:
Application
Filed:
June 15, 2021
Publication date:
October 21, 2021
Applicant:
GLYCOMIMETICS, INC.
Inventors:
John L. MAGNANI, John M. PETERSON, Myung-Gi BAEK
Abstract: Compounds, compositions, and methods for treatment and/or prevention of at least one disease, disorder, and/or condition by inhibiting binding of an E-selectin to an E-selectin ligand are disclosed. For example, highly potent multimeric E-selectin antagonist are desorbed and pharmaceutical compositions comprising at least one of the same.
Type:
Grant
Filed:
October 6, 2017
Date of Patent:
July 27, 2021
Assignee:
GLYCOMIMETICS, INC.
Inventors:
John L. Magnani, John M. Peterson, Myung-Gi Baek
Abstract: Compounds, compositions, and methods for the diagnosis and/or treatment of medical conditions involving infections with and colonization by Pseudomonas bacteria including, for example, Pseudomonas aeruginosa in the lungs of patients with cystic fibrosis are described.
Abstract: Methods are disclosed for the mobilization of marrow infiltrating cells (MILs) using E-selectin antagonists for the treatment of disorders such as cancer. Methods for treating or preventing cancers using MILs mobilized by E-selectin antagonists are further disclosed.