Quadriga Biosciences, Inc.

Xenoport, Inc.

Symyx Technologies, Inc.

Acorda Therapeutics, Inc.

Maxymune Therapeutics, Inc.

Bernd Jandeleit

Wolf-Nicolas Fischer

Kerry J Koller

Mark A Gallop

Yunxiao Li

Noa Zerangue

Ralph B Nielsen

Gerrit Klaerner

Gordon Ringold

Anil S Guram

Timothy S Powers

Dominique Charmot

Thomas R Boussie

Paul Mansky

Adam Luke Safir

Laxminarayan Bhat

Anne Marie Lapointe

Peter Virsik

Didier G Benoit

Cheryl Lund

Peter Huefner

Keith R Bley

Xiaohong Bei

Peter Y Tam

Shixiang Yan

Laura T Mazzola

Thomas Crevier

Guangyao Gao

Ruifang Liu

Phenylalanine-based inhibitors of the Large Amino Acid Transporter 1 (LAT1) are disclosed. The compounds are useful in modulating the transcellular transport of substrates of LAT1 such as large neutral amino acids. The compounds are useful in immunomodulation therapies.

Phenylalanine-based LAT1 inhibitors and uses thereof

&#x3b2;-Substituted &#x3b2;-amino acids, &#x3b2;-substituted &#x3b2;-amino acid derivatives, and &#x3b2;-substituted &#x3b2;-amino acid analogs and (bio)isosteres and their use as chemotherapeutic agents are disclosed. The &#x3b2;-substituted &#x3b2;-amino acid derivatives and &#x3b2;-substituted &#x3b2;-amino acid analogs and (bio)isosteres are selective LAT1/4F2hc substrates and exhibit rapid uptake and retention in tumors expressing the LAT1/4F2hc transporter. Methods of synthesizing the &#x3b2;-substituted &#x3b2;-amino acid derivatives and &#x3b2;-substituted &#x3b2;-amino acid analogs and methods of using the compounds for treating cancer are also disclosed. The &#x3b2;-substituted &#x3b2;-amino acid derivatives and &#x3b2;-substituted &#x3b2;-amino acid analogs exhibit selective uptake in tumor cells expressing the LAT1/4F2hc transporter and accumulate in cancerous cells when administered to a subject in vivo. The &#x3b2;-substituted &#x3b2;-amino acid derivatives and &#x3b2;-substituted &#x3b2;-amino acid analogs and (bio)isosteres exhibit cytotoxicity toward several tumor types.

&#x3b2;-substituted &#x3b2;-amino acids and analogs as chemotherapeutic agents

Beta-substituted beta-amino acids and analogs as chemotherapeutic agents and uses thereof

Beta-substituted beta-amino acids and analogs as chemotherapeutic agents

&#x3b2;-substituted &#x3b2;-amino acids and analogs as chemotherapeutic agents and uses thereof

&#x3b2;-Substituted &#x3b3;-amino acids, &#x3b2;-substituted &#x3b3;-amino acid derivatives, and &#x3b2;-substituted &#x3b3;-amino acid analogs and (bio)isosteres and their use as chemotherapeutic agents are disclosed. The &#x3b2;-substituted &#x3b3;-amino acid derivatives and &#x3b2;-substituted &#x3b3;-amino acid analogs and (bio)isosteres are selective LAT1/4F2hc substrates, capable of passing through the blood-brain barrier, and exhibit rapid uptake and retention in tumors expressing the LAT1/4F2hc transporter. Methods of synthesizing the &#x3b2;-substituted &#x3b3;-amino acid derivatives and &#x3b2;-substituted &#x3b3;-amino acid analogs and (bio)isosteres and methods of using the compounds for treating tumors are also disclosed. The &#x3b2;-substituted &#x3b3;-amino acid derivatives and &#x3b2;-substituted &#x3b3;-amino acid analogs and (bio)isosteres exhibit an improved selectivity toward tumor cells expressing the LAT1/4F2hc transporter and accumulate in cancerous cells when administered to a subject in vivo. The &#x3b2;-substituted &#x3b3;-amino acid derivatives and &#x3b2;-substituted &#x3b3;-amino acid analogs and (bio)isosteres exhibit an increased efficacy on a variety of tumor types.

&#x3b2;-substituted &#x3b3;-amino acids and analogs as chemotherapeutic agents

Acetaminophen conjugates are provided, which have an acetaminophen moiety covalently linked to a second moiety. The conjugates provided may have one or more advantageous properties, including increased water solubility as compared to acetaminophen, reduced toxicity profile as compared to acetaminophen and an altered pharmacokinetic profile. Formulations comprising the conjugates are also provided, as are methods of using the conjugates and kits comprising the conjugates.

Acetaminophen conjugates, compositions and methods of use thereof

Acyloxyalkyl carbamate prodrugs of trans-4-(aminomethyl)-cyclohexanecarboxylic acid, pharmaceutical compositions thereof, methods of making prodrugs of trans-4-(aminomethyl)-cyclohexane-carboxylic acid, and methods of using prodrugs of trans-4-(aminomethyl)-cyclohexanecarboxylic acid and pharmaceutical compositions thereof to treat or prevent various diseases or disorders are disclosed. Acyloxyalkyl carbamate prodrugs of trans-4-(aminomethyl)-cyclohexanecarboxylic acid and pharmaceutical compositions thereof suitable for oral and topical administration and for administration using sustained release dosage forms are also disclosed.

Acyloxyalkyl carbamate prodrugs of tranexamic acid, methods of synthesis and use

Pantoic acid ester neopentyl sulfonyl ester prodrugs of acamprosate, pharmaceutical compositions comprising such prodrugs, and methods of using such prodrugs and compositions thereof for treating diseases are disclosed. In particular, acamprosate prodrugs exhibiting enhanced oral bioavailability and methods of using acamprosate prodrugs to treat neurodegenerative disorders, psychotic disorders, mood disorders, anxiety disorders, somatoform disorders, movement disorders, substance abuse disorders, binge eating disorder, cortical spreading depression related disorders, tinnitus, sleeping disorders, multiple sclerosis, and pain are disclosed.

Complex pantoic acid ester neopentyl sulfonyl ester cyclization release prodrugs of acamprosate, compositions thereof, and methods of use

Simple pantoic acid ester neopentyl sulfonyl ester cyclization release prodrugs of acamprosate, compositions thereof, and methods of use

Growing community of inventors

Menlo Park, CA, United States of America

Bernd Jandeleit