Delving into the Latest Updates on MK-3168 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug, Diagnostic radiopharmaceuticals

Synonyms

Target

FAAH

Mechanism

FAAH inhibitors(Anandamide amidohydrolase inhibitors), PET imaging(Positron-emission tomography enhancers)

Therapeutic Areas

Other DiseasesNervous System Diseases

Active Indication-

Inactive Indication

Alcohol Use DisorderBehavioural disordersNervous System Diseases+ [1]

Originator Organization

Merck Sharp & Dohme Corp.

Active Organization

Celgene Corp.

Inactive Organization

Yale University

Merck Sharp & Dohme Corp.Janssen Research & Development LLC

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC21H21ClN4OS

InChIKeyWRBFPGYDKJBYBI-LGNYVVAJSA-N

CAS Registry1242441-58-2

A Phase 1, Open-label, Multi-part Positron Emission Tomography (PET) Imaging Study to Evaluate the Biodistribution and Radiation Dosimetry of the Monoacylglycerol Lipase (MGLL) PET Ligand [18F]T-401 and to Evaluate Fatty Acid Amide Hydrolase (FAAH) and MGLL Enzyme Availability in the Central Nervous System Using [11C]MK-3168 and [18F]T-401 PET Ligands Before and After Oral Administration of Single and Multiple Doses of CC-97489 in Healthy Adult Subjects

The purpose of this study is to evaluate enzyme availability in the central nervous system before and after CC-97489 administration in healthy participants

Start Date24 Sep 2021

Sponsor / Collaborator

Celgene Corp.

NCT04404712

/ TerminatedEarly Phase 1IIT

FAAH Availability in Psychiatric Disorders: A PET Study

The aim of the present study is to examine Fatty Acid Amide Hydrolase (FAAH) availability in humans, including healthy individuals and across a spectrum of psychiatric disorders in which alterations in the endocannabinoid system are observed.

Start Date23 Sep 2020

Sponsor / Collaborator

Yale University

NCT02169973

/ CompletedPhase 1

An Open-Label Study to Investigate the Regional Brain Kinetics of the Positron Emission Tomography Ligand 11C-MK-3168 and the Blocking of the Retention of the Ligand in the Human Brain by JNJ-42165279

The purpose of the study is to measure the uptake, distribution, and clearance of 11C-MK-3168 by Positron Emission Tomography (PET) scan and to model the tissue specific kinetics of 11C-MK-3168 with the appropriate input function in human brain in Part A; to measure blocking of retention of 11C-MK-3168 at the estimated time to maximum plasma concentration after dosing (tmax) following each single oral doses of JNJ-42165279 and model the exposure/enzyme interaction of JNJ-42165279 in Part B; to measure the saturation of enzyme inhibition in the brain at steady state plasma concentrations of JNJ-42165279 (on Day 8) after 7 once-daily doses of JNJ-42165279 by conducting PET studies with 11C-MK-3168 at trough plasma concentrations on Day 2 in Part C.

Start Date01 Feb 2014

Sponsor / Collaborator

Janssen Research & Development LLC

100 Clinical Results associated with MK-3168

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100 Translational Medicine associated with MK-3168

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100 Patents (Medical) associated with MK-3168

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2

Literatures (Medical) associated with MK-3168

01 Jul 2018·Clinical and Translational Science

Fatty Acid Amide Hydrolase Inhibition by JNJ‐42165279: A Multiple‐Ascending Dose and a Positron Emission Tomography Study in Healthy Volunteers

Article

Author: Celen, Sofie ; Pemberton, Darrel J. ; Zannikos, Peter ; Palmer, James A. ; van Laere, Koen ; van den Boer, Maarten ; Bormans, Guy ; Schmidt, Mark E. ; Rassnick, Stef ; Postnov, Andrey ; de Hoon, Jan ; van der Ark, Peter ; van Hecken, Anne

AbstractInhibition of fatty acid amide hydrolase (FAAH) potentiates endocannabinoid activity and is hypothesized to have therapeutic potential for mood and anxiety disorders and pain. The clinical profile of JNJ‐42165279, an oral selective FAAH inhibitor, was assessed by investigating the pharmacokinetics, pharmacodynamics, safety, and binding to FAAH in the brain of healthy human volunteers. Concentrations of JNJ‐42165279 (plasma, cerebrospinal fluid (CSF), urine) and fatty acid amides (FAA; plasma, CSF), and FAAH activity in leukocytes was determined in a phase I multiple ascending dose study. A positron emission tomography study with the FAAH tracer [11C]MK3168 was conducted to determine brain FAAH occupancy after single and multiple doses of JNJ‐42165279. JNJ‐42165279 administration resulted in an increase in plasma and CSF FAA. Significant blocking of brain FAAH binding of [11C]MK3168 was observed after pretreatment with JNJ‐42165279. JNJ‐42165279 produces potent central and peripheral FAAH inhibition. Saturation of brain FAAH occupancy occurred with doses ≥10 mg of JNJ‐42165279. No safety concerns were identified.

13 Jun 2013·ACS Medicinal Chemistry LettersQ3 · MEDICINE

Discovery of MK-3168: A PET Tracer for Imaging Brain Fatty Acid Amide Hydrolase

Q3 · MEDICINE

Article

Author: Abbadie, Catherine ; Guo, Yan ; Jin, Hong ; Sanabria, Sandra ; Chobanian, Harry ; Posavec, Diane ; Salituro, Gino ; Chioda, Marc ; Shiao, Lin-Lin ; Chang, Linda ; Madeira, Maria ; Hamill, Terence G ; DeVita, Robert J ; Holahan, Marie ; Hong, Qingmei ; Alexander, Jessica ; Jochnowitz, Nina ; Rosenbach, Mark ; Lin, Linus S ; Terebetski, Jenna L ; Purcell, Mona ; Powell, Joyce ; O'Malley, Stacey ; Hajdu, Richard ; Chen, Tsing-Bau ; Karanam, Bindhu ; Nargund, Ravi P ; Bakshi, Raman ; Cook, Jacquelynn ; Sullivan, Kathleen A ; Mandala, Suzanne ; Dellureficio, James ; Williams, David ; Liu, Ping ; Riffel, Kerry ; Miller, Patricia ; Hargreaves, Richard ; Williams, Mangay ; Leone, Joseph F ; Zeng, Zhizhen ; Joshi, Aniket ; Li, Wenping ; Xu, Ling ; Fung, Selena

We report herein the discovery of a fatty acid amide hydrolase (FAAH) positron emission tomography (PET) tracer. Starting from a pyrazole lead, medicinal chemistry efforts directed toward reducing lipophilicity led to the synthesis of a series of imidazole analogues. Compound 6 was chosen for further profiling due to its appropriate physical chemical properties and excellent FAAH inhibition potency across species. [(11)C]-6 (MK-3168) exhibited good brain uptake and FAAH-specific signal in rhesus monkeys and is a suitable PET tracer for imaging FAAH in the brain.

100 Deals associated with MK-3168

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