Johns Hopkins University

Institute of Organic Chemistry and Biochemistry Ascr, V.v.i.

Ústav Organické Chemie a Biochemie Av {hacek Over (c)}r, V.v.i.

Ustav Organicke Chemie a Biochemie Av Cr, V.v.i.

Institute of Organic Chemistry & Biochemistry

Adarga Limited

Inst of Organic Chem. and Biochemistry As Cr V.v.i

Rana Rais

Barbara S Slusher

Pavel Majer

Andrej Jancarik

Lukas Tenora

Tomas Tichy

Marcela Krecmerova

Jan Vavra

Luis Garza

Xuhang Li

Mohameed Islam

Gregory J Riggins

Ivan Snajdr

James Vornov

Katerina Novotna

Diane E Peters

Michael Nedelcovych

Clemens Kratochwil

Jesse Alt

Benjamin Bell

The use of a class of prodrugs of 2-PMPA that alter tissue distribution of 2-PMPA to non-prostate tissues is disclosed. The presently disclosed prodrugs preferentially distribute to healthy tissues including the kidney, lacrimal glands, and salivary glands, which represent sites of off-target binding and toxicity for PSMA-targeted prostate cancer imaging agents and therapies. Accordingly, the 2-PMPA prodrugs can be used to pretreat, bind to, and shield the kidney and salivary glands from PSMA-targeted cytotoxic or radiotherapy.

Prodrugs of 2-PMPA for healthy tissue protection during PSMA-targeted cancer imaging or radiotherapy

Methods for the use of prodrugs of itaconic acid and 1- and 4-methyl itaconic acid for inducing hair growth and treating an inflammatory, or immune activation (adaptive or innate), skin condition or other condition associated with hair loss are disclosed.

Use of itaconate and its derivatives/analogues to induce hair growth

Prodrugs of itaconic acid and 1- and 4-methyl itaconic acid and their use for treating a disease, disorder, or condition associated with inflammation are disclosed.

Prodrugs of itaconate and methyl itaconate

Glutamine antagonists and their use for treating oncological, immunological, and neurological diseases are disclosed. Also disclosed are methods for treating an oncological, immunological, infectious or neurological disease or disorder, the method comprising administering to a subject in need of treatment thereof a therapeutically effective amount of a glutamine antagonist of the disclosure or the pharmaceutical composition thereof. Also disclosed are methods of enhancing the effects of an immune checkpoint inhibitor, enabling a subject to respond to an immune checkpoint inhibitor, or enabling the toxicity or the dose or number of treatments with an immune checkpoint inhibitor to be reduced, comprising administering to a subject in need of treatment thereof a therapeutically effective amount of a glutamine antagonist of the disclosure or the pharmaceutical composition thereof, and an immune checkpoint inhibitor. Also disclosed are methods for treating an oncological, immunological, infectious or neurological disease or disorder that is refractory to checkpoint inhibitor therapy, the method comprising administering to a subject in need thereof, and having the refractory disease or disorder, a therapeutically effective amount of a glutamine antagonist of the disclosure or the pharmaceutical composition thereof.

Glutamine antagonists and uses thereof

Methods and compounds are disclosed for treating a disease or condition by inhibiting PSMA (Prostate Specific Membrane Antigen) using prodrugs of 2-PMPA.

Prodrugs of prostate specific membrane antigen (PSMA) inhibitor

The disclosure provides compounds having formula (I): and the pharmaceutically acceptable salts thereof, wherein R, R, R′, and X are as defined as set forth in the specification. Compounds having formula (I) are prodrugs that release glutamine analogs, e.g., 6-diazo-5-oxo-L-norleucine (DON). The disclosure also provides compounds having formula (I) for use in treating cancer.

Prodrugs of glutamine analogs

Prodrugs of hydroxamate-based GCPII inhibitors and methods of their use for treating a disease or condition are disclosed.

Prodrugs of hydroxamate-based GCPII inhibitors

Prodrugs of mebendazole and methods for their use in treating a disease, disorder, or disorder, including cancer, are disclosed.

Mebendazole prodrugs with enhanced solubility and oral bioavailability

Methods for buccally, sublingually, or intranasally administering a prodrug of propofol to a subject in need of treatment thereof in an amount sufficient to deliver a therapeutically effective amount of propofol to the subject are disclosed.

Buccal, sublingual and intranasal delivery of fospropofol

Prodrug compositions and utility of hydroxamate-based GCPII inhibitors

The disclosure provides compounds having formula (I): and the pharmaceutically acceptable salts thereof, wherein R, R, R', and X are as defined as set forth in the specification. Compounds having formula (I) are prodrugs that release glutamine analogs, e.g., 6-diazo-5-oxo-L-norleucine (DON). The disclosure also provides compounds having formula (I) for use in treating cancer.

Methods and compounds are disclosed for treating inflammatory bowel disease (IBD) by using Prostate Specific Membrane Antigen (PSMA) inhibitors.

Growing community of inventors

West Friendship, MD, United States of America

Rana Rais