Delving into the Latest Updates on [11C]ER-176 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug, Diagnostic radiopharmaceuticals

Synonyms

11C-ER176

Target

TSPO

Mechanism

TSPO inhibitors(Translocator protein inhibitors), PET imaging(Positron-emission tomography enhancers)

Therapeutic Areas

Immune System DiseasesNervous System DiseasesOther Diseases

Active Indication

Multiple SclerosisAlzheimer Disease

Inactive Indication

MyositisRheumatoid Arthritis

Originator Organization

University of Pisa

Active Organization

THE METHODIST HOSP RESEARCH INSTITUTE

Mayo Clinic

National Institute on Aging

Inactive Organization

National Institute of Mental HealthNational Institutes of Health Clinical Center

Drug Highest PhasePhase 2/3

First Approval Date-

Regulation-

Structure

Molecular FormulaC20H20ClN3O

InChIKeyASFLYNMYGAYKON-XFBLKYPGSA-N

CAS Registry1623028-18-1

Chronic sleep restriction is ubiquitous in both the general population and the military. The deleterious effects of sleep loss on human alertness and cognitive performance have been documented in numerous studies dating back to the nineteenth century. Over the past decade, evidence has emerged indicating that chronic sleep restriction may also precipitate deleterious, long lasting neuropathological changes in the brain. The purpose of this study is to determine neuropathological effects of sleep restriction and identify physiological mechanisms that correlate with sleep loss-induced performance impairment.

Start Date23 May 2023

Sponsor / Collaborator

Walter Reed Army Institute of Research

[+2]

NCT06384378 / RecruitingPhase 2IIT

Central and Peripheral Immune Cross-talk in Alzheimer's Disease and Their Modulation by a Novel Immunotherapy

Inflammation could provide a new focus for therapeutic intervention. In this study, we will measure blood and cerebrospinal fluid (CSF) inflammation biomarkers and compare them to measurements of brain glial activation obtained by positron emission tomography (PET). In addition, we will determine the effect of low-dose interleukin-2 (IL-2) immunotherapy, given over 22 weeks, on these inflammation biomarkers.

Start Date17 Mar 2023

Sponsor / Collaborator

THE METHODIST HOSP RESEARCH INSTITUTE

100 Clinical Results associated with [11C]ER-176

Login to view more data

100 Translational Medicine associated with [11C]ER-176

Login to view more data

100 Patents (Medical) associated with [11C]ER-176

Login to view more data

7

Literatures (Medical) associated with [11C]ER-176

01 Nov 2022·Drug Development Research

Acetamidobenzoxazolone scaffold as a promising translocator protein (18 kDa, TSPO) marker for neuroinflammation imaging: Advancement in last decennial period

Review

Author: Tiwari, Anjani Kumar ; Zhang, Ming‐Rong ; Adhikari, Anupriya

AbstractInflammation has been linked to the onset and progression of a wide range of neuropathological disorders. The well‐conserved outer mitochondrial membrane 18 kDa translocator protein (TSPO) is perceived as an in vivo neuroinflammation marker. A dearth of a reference region, genetic disparity influencing the ligand's affinity for TSPO, and a substantial signal in the endothelium of the brain veins contributes toward complications in quantifying TSPO positron emission tomography (PET) image. Up to the present time several radiotracers based on different pharmacophore such as (R)[11C]PK11195, [18F]DPA714, [11C]PBR28, [11C]ER176, and many more have been recognized for envisaging the prominent TSPO level observed in neurological conditions. Recently acetamidobenzoxazolone (ABO) scaffold, a bicyclic ring system composed of a phenyl ring fused to a carbamate and its substituted radiolabelled analogues especially at C‐5 position has evidenced encouraging outcomes as next generation of TSPO PET ligands. Diverse ABO framework‐based TSPO ligands have been designed embracing imperative aspects such as lipophilicity, metabolic profile, and capability to penetrate the blood–brain barrier apart from least effect of polymorphism (rs6971). Over the years numerous systematic literature reviews compiling different structural class of TSPO ligands characterized on the grounds of their binding affinity and metabolite profile have been reported but none is especially focused toward a fascinating benzoxazolone scaffold. This review exclusively bestows an overview of the recent advancements on ABO derivatives with neuroinflammation imaging potential and emphases on the structural features accountable for visualizing TSPO in‐vivo with collation of published reports during last 10 years.

04 Jul 2022·Molecular Pharmaceutics

[¹⁸F]BIBD-239: ¹⁸F-Labeled ER176, a Positron Emission Tomography Tracer Specific for the Translocator Protein

Article

Author: Yan, Jun ; Yu, Ziyue ; Chen, Hualong ; Liu, Yajing ; Wu, Zehui ; Jiang, Zeng ; Cheng, Xuebo ; Yang, Tingyu ; Ji, Xunming ; Sun, Yuli ; Zhang, Lu ; Zheng, Wei

[¹¹C]ER176 has adequate sensitivity to image the human brain translocator protein (TSPO) in all three genotypes by positron emission tomography (PET). However, its clinical application is limited by the short half-life of ¹¹C (20.38 min). To overcome the deficiency of [¹¹C]ER176 and keep the pharmacophore features of ER176 to the maximum extent, we designed four fluorine-labeled ER176 derivatives using the deuterium method. In vitro competition binding confirmed that the designed compounds had high affinity for TSPO. Biodistribution experiments showed that tissues with high expression of TSPO had high uptake of these compounds, as well as that the compound showed high brain penetration and mild defluorination in vivo. Therefore, [¹⁸F]BIBD-239 with simple synthesis conditions was selected for further biological evaluation. Theoretical simulations showed that BIBD-239 and ER176 have similar binding modes and sites to Ala147-TSPO and Thr147-TSPO, which indicated that the tracers may have consistent sensitivity to the three affinity genotypes. In vitro autoradiography and in vivo PET studies of the ischemic rat brain showed dramatically higher uptake of [¹⁸F]BIBD-239 on the lesion site compared to the contralateral side with good brain kinetics. Additionally, [¹⁸F]BIBD-239 provided clear tumor PET images in a GL261 glioma model. Importantly, PET imaging and liquid chromatography-high-resolution mass spectrometry (LC-HRMS) results showed that in vivo defluorination and other metabolites of [¹⁸F]BIBD-239 did not interfere with brain imaging. Conclusively, [¹⁸F]BIBD-239, similar to ER176 with low polymorphism sensitivity, has simple labeling conditions, high labeling yield, high affinity, and high specificity for TSPO, and it is planned for further evaluation in higher species.

01 Dec 2021·Applied Radiation and IsotopesQ3 · ENGINEERING & TECHNOLOGY

Alternative strategies for the synthesis of [11C]ER176 for PET imaging of neuroinflammation

Q3 · ENGINEERING & TECHNOLOGY

Article

Author: Aluicio-Sarduy, Eduardo ; Murali, Dhanabalan ; Engle, Jonathan W ; Barnhart, Todd E ; Ellison, Paul A ; DiFilippo, Alexandra H ; Mixdorf, Jason C ; Christian, Bradley T ; Xin, Yangchun

[¹¹C]ER176 is a next generation PET radioligand for imaging 18 kDa translocator protein, a biomarker for neuroinflammation. The goal of this work was to investigate alternative strategies for the radiochemical synthesis, purification, and formulation of [¹¹C]ER176. An optimized tri-solvent high-performance liquid chromatography (HPLC) protocol is described to separate the hydro-de-chlorinated byproduct from [¹¹C]ER176. A newly implemented solid phase extraction work-up efficiently removed HPLC solvent while maintaining chemical purity and overall radiochemical yield and purity. This new HPLC purification and final formulation was completed within 40 min, providing 2.7 ± 0.5 GBq of [¹¹C]ER176 at end of synthesis with 1400 ± 300 GBq/μmol molar activity while meeting all specifications for radiopharmaceutical quality control tests for human research use.

100 Deals associated with [11C]ER-176

Login to view more data

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Multiple Sclerosis	Phase 2	US	Mayo Clinic	10 Apr 2023
Alzheimer Disease	Phase 2	US	National Institute on Aging	11 May 2021
Dementia	IND Application	US	National Institute of Mental Health	03 Jul 2019
Dementia	IND Application	US	National Institutes of Health Clinical Center	03 Jul 2019
Myositis	IND Application	US	National Institute of Mental Health	14 Jun 2019
Myositis	IND Application	US	National Institutes of Health Clinical Center	14 Jun 2019
Rheumatoid Arthritis	IND Application	US	National Institutes of Health Clinical Center	14 Jun 2019
Rheumatoid Arthritis	IND Application	US	National Institute of Mental Health	14 Jun 2019

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03958630 (CTgov)	Phase 1	Neuroinflammation \| Neurodegenerative Diseases \| Dementia	13	Positron Emission Tomography (PET) Scan+11C-ER176+11C-PIB (Healthy Volunteers)	vwqeudvuqy(vjagmwjogk) = lhedfxdhlz lftfquytdn (xzugjomczx, ukqujzmnew - macudifiho) View more	-	01 May 2024
				Positron Emission Tomography (PET) Scan+11C-ER176+11C-PIB (Subjects With Frontotemporal Dementia (FTD))	vwqeudvuqy(vjagmwjogk) = ikmatnwuzv lftfquytdn (xzugjomczx, vyowdqwbns - seyilflpep) View more
NCT04762719 (CTgov)	Phase 2/3	Diabetic Gastroparesis	12	Core biopsy of gastric muscle+PET/CT Scan (Diabetic Gastroparesis Subjects)	xjgncfnkuu(ecrbgourkm) = qmammaidsp cfdfzutqsj (vjvdlbamoo, xytzqatpxq - mttrqdumfi) View more	-	18 Apr 2023
				PET/CT Scan (Diabetic Without Gastroparesis Subjects)	xjgncfnkuu(ecrbgourkm) = ctarakvpsb cfdfzutqsj (vjvdlbamoo, iomfhplguo - xlfphpekwu) View more
NCT03744312 (CTgov)	Phase 1/2	Alzheimer Disease \| Inflammation	9	Florbetaben+11C-ER176 (Cognitive Impairment)	pvvniijnqp(hlrfytyirt) = rtzkcmxfyv wxoocysotw (bbhaqxrebm, goqmrixywy - spbqinknyr) View more	-	13 Sep 2023
				Florbetaben+11C-ER176 (No Cognitive Impairment)	pvvniijnqp(hlrfytyirt) = xnyrathjfk wxoocysotw (bbhaqxrebm, rbuhuuwqcy - fryuwjqmwx) View more