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

开始日期2021-09-24

申办/合作机构

Celgene Corp.

NCT04404712 / Terminated早期临床1期IIT

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.

开始日期2020-09-23

申办/合作机构

Yale University

NCT02169973 / Completed临床1期

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.

开始日期2014-02-01

申办/合作机构

Janssen Research & Development LLC

100 项与 MK-3168 相关的临床结果

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100 项与 MK-3168 相关的转化医学

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100 项与 MK-3168 相关的专利（医药）

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项与 MK-3168 相关的文献（医药）

2018-07-01·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

作者: Celen, Sofie ; Pemberton, Darrel J. ; Zannikos, Peter ; Palmer, James A. ; van den Boer, Maarten ; van Laere, Koen ; 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.

2013-06-13·ACS Medicinal Chemistry Letters3区 · 医学

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

3区 · 医学

Article

作者: Guo, Yan ; Abbadie, Catherine ; Jin, Hong ; Chobanian, Harry ; Sanabria, Sandra ; Salituro, Gino ; Posavec, Diane ; Chioda, Marc ; Shiao, Lin-Lin ; Chang, Linda ; Madeira, Maria ; Hamill, Terence G ; DeVita, Robert J ; Hong, Qingmei ; Holahan, Marie ; Jochnowitz, Nina ; Alexander, Jessica ; Rosenbach, Mark ; Lin, Linus S ; Purcell, Mona ; Terebetski, Jenna L ; 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 项与 MK-3168 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
诊断试剂	临床3期	-	Merck Sharp & Dohme Corp.	-
酒精使用障碍	临床1期	美国	Yale University	2020-09-23
行为障碍	临床1期	美国	Yale University	2020-09-23
精神障碍	临床1期	美国	Yale University	2020-09-23
创伤后应激障碍	临床1期	美国	Yale University	2020-09-23