Johns Hopkins University

Institute of Organic Chemistry & Biochemistry

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

Camilo Rojas

Barbara S Slusher

Takashi Tsukamoto

Norman J Haughey

Ajit G Thomas

Niyada Hin

Dana Victor Ferraris

Xin Hu

Marc Ferrer

Bridget Duvall

Michal Sala

Michael Polydefkis

Ondrej Stepanek

Hubert Hrebabecky

Radim Nencka

Marigo Stathis

Jesse Alt

Michal SÁLA

Small molecule inhibitors of neutral sphingomyelinase 2 (nSMase2) and their use for treating neurodegenerative diseases, such as, neurodegenerative diseases associated with high levels of ceramide, including, but not limited to Alzheimer's disease (AD), HIV-associated neurocognitive disorder (HAND), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS), and, in other aspects, for treating cancer or HIV-1, are provided.

Small molecule neutral sphingomyelinase 2 (nSMase2) inhibitors

Methods for treating one or more diseases associated with neutral sphingomyelinase 2 (nSMase2) in a subject in need of treatment thereof, the method comprising administering to the subject a therapeutically effective amount of 2,6-dimethoxy-4-(5-phenyl-4-thiophen-2-yl-1H-imidazol-2-yl)-phenol (DPTIP) or a pharmaceutically acceptable salt thereof, are disclosed.

2,6-dimethoxy-4-(5-phenyl-4-thiophene-2-yl-1H-imidazol-2-yl)-phenol (DPTIP) a small molecule inhibitor of neutral sphingomyelinase 2 (nSMase-2) for the treatment of neurodegenerative and oncologic diseases

Methods for treating a Human Immunodeficiency Virus (HIV) infection comprising administering to a subject in need of treatment thereof an effective amount of a small molecule nSMase2 inhibitor.

Inhibition of nSMase for the treatment of human immunodeficiency virus infection

Small molecule inhibitors of neutral sphingomyelinase 2 (nSMase2) and their use for treating neurodegenerative diseases, such as, neurodegenerative diseases associated with high levels of ceramide, including, but not limited to Alzheimer's disease (AD), HIV-associated neurocognitive disorder (HAND), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS), and, in other aspects, for treating cancer, are provided.

Small molecule inhibitors of neutral sphingomyelinase 2 (nSMase2) for the treatment of neurodegenerative diseases

D-amino acid oxidase (DAAO) inhibitors and methods of their use, either alone or in combination with D-serine or D-alanine, to facilitate allosteric activation of NMDA receptor-mediated neurotransmission and methods of their use as therapeutic agents for treating a subject afflicted with one or more cognitive-disorders, such as schizophrenia, including subjects suffering from negative symptoms and cognitive impairments, post-traumatic stress disorder (PTSD), or pain, are disclosed.

Inhibitors of D-amino acid oxidase

Described herein are high-throughput methods of monitoring D-serine levels in plasma. The assay involves the use of strong cation solid phase extraction (SPE) to isolate D-serine from plasma, followed by quantitation of D-serine using the D-amino acid oxidase- (DAAO-) catalyzed reaction. Also described are methods of screening for compounds that act as DAAO inhibitors.

High-throughput methods for determining pharmacological levels of plasma D-serine

Provided herein are methods for quantitating glutamate carboxypeptidase II activity in a biological sample, such as a skin biopsy sample, and for determining whether an agent is inhibiting GCP in a subject.

Quantitation of GCP activity in biological samples

Growing community of inventors

Baltimore, MD, United States of America

Camilo Rojas