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NTRX-07

A potent and selective CB2 agonist

Immune cells, including microglia within the central nervous system, express CB2 receptors. When activated these receptors can modulate immune cell migration and cytokine release decreasing pro-inflammatory responses. For this reason, CB2 receptors have become the subject of considerable research as a potential therapeutic target to treat a host of neuro-inflammatory disorders.

NTRX%20Decreases%20Inflammation_edited.j

NTRX-07 is an ideal therapeutic candidate with high affinity for the CB2 receptor while avoiding the adverse psychotropic effects that accompany CB1 receptor-based therapies. Furthermore, it  penetrates the blood-brain barrier providing for high expression levels in the CNS.
 

Multiple pre-clinical studies have demonstrated that NTRX-07 promotes neuronal survival through decreasing pro-inflammatory microglial activity.

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NTRX-07 has been shown to decrease neuroinflammation, improve A-beta clearance and improve memory loss observed in Alzheimer disease rodent models.

Pre-clinical efficacy has also been established in multiple neuropathic pain models, including chemotherapy-induced peripheral neuropathy (CIPN), nerve ligation, and complex regional pain syndrome (CRPS) induced by ischemic injury.

 

NTRX-07 has passed all basic ADMET testing as well as genotoxicity and in-vitro cardiac safety; no in vivo toxicology or psychomimetic effects have been observed. Preclinical safety studies at high doses have shown a good safety profile.

The FDA has issued an IND for NTRX-07 and a Phase I safety study in normal volunteers has been completed. The drug was well tolerated at expected therapeutic doses and no serious adverse event were identified.

ALZHEIMER’S DISEASE MODEL

Key Publications

BIE, B, WU, J, B, YANG, H, XU, J, BROWN, DL. NAGUIB, M. SUPPRESSION OF NEUROLIGIN 1 UNDERLIES AMYLOID-INDUCED MEMORY DEFICIENCY. NATURE NEUROSCIENCE, 2014;17:223-31

WU, J, BIE, B, YANG, H, XU, J, BROWN, DL. NAGUIB, M. ACTIVATION OF THE CB2 RECEPTOR SYSTEM REVERSES AMYLOID-INDUCED MEMORY DEFICIENCY. NEUROBIOLOGY OF AGING 2012. 2013;34:791-804.

WU, J, BIE, B, YANG, H, XU, J, BROWN, DL. NAGUIB, M. SUPPRESSION OF CENTRAL CHEMOKINE FRACTALKINE SIGNALING ALLEVIATES AMYLOID-INDUCED MEMORY DEFICIENCY. NEUROBIOLOGY OF AGING, 2013;34:2843-2852.

NAGUIB M, BIE B, TING AH. FUNDAMENTAL CONCEPTS OF EPIGENETICS FOR CONSIDERATION IN ANESTHESIOLOGY. CURRENT OPINION IN ANESTHESIOLOGY. 2012; 25:434-443.

NEUROPATHIC PAIN MODEL

Key Publications

NAGUIB M, XU JJ, DIAZ P, BROWN DL, BIE B, HU J, CRAIG S, HITTELMAN WN. PREVENTION OF PACLITAXEL-INDUCED NEUROPATHY THROUGH ACTIVATION OF THE CENTRAL CANNABINOID TYPE 2 RECEPTOR SYSTEM. ANESTHESIA & ANALGESIA 2012;114:1104-1120.

NAGUIB M, DIAZ F, XU JJ, ASTRUC-DIAZ F, CRAIG S, VIVAS-MEJIA PE, BROWN DL. MDA7: A NOVEL SELECTIVE CANNABINOID RECEPTOR 2 AGONIST THAT PREVENTS ALLODYNIA IN RODENT NEUROPATHIC PAIN MODELS. BRITISH JOURNAL OF PHARMACOLOGY 2008; 155: 1104-1116

XU JJ, DIAZ P, BIE, B, WU J, ASTRUC-DIAZ F, BROWN DL, NAGUIB M. SPINAL GENE EXPRESSION PROFILING AND PATHWAYS ANALYSES OF A CB2 AGONIST (MDA7)-TARGETED PREVENTION OF PACLITAXEL-INDUCED NEUROPATHY. NEUROSCIENCE 2014;260:185-94.

XU JJ, DIAZ F, ASTRUC-DIAZ F, CRAIG S, MUNOZ E, AND NAGUIB M. PHARMACOLOGICAL CHARACTERIZATION OF A NOVEL CANNABINOID LIGAND, MDA19, FOR TREATMENT OF NEUROPATHIC PAIN. ANESTHESIA AND ANALGESIA 2010; 111: 99-109.

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