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

Action

inhibitors

Mechanism

TSPO inhibitors(Translocator protein inhibitors)

Therapeutic Areas

Nervous System DiseasesOther DiseasesImmune System Diseases+ [1]

Active Indication

NeuroinflammationAlzheimer DiseaseInflammation+ [2]

Inactive Indication

Amyotrophic Lateral SclerosisAphasia, Primary ProgressiveDiabetic Gastroparesis+ [5]

Originator Organization

University of Pisa

Active Organization

National Institute of Mental Health

Columbia University

National Institute on Aging

+ [1]

Inactive Organization-

License Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure/Sequence

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 Hospital Research Institute

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

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

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

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12

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

15 Jun 2024·Journal of Labelled Compounds and Radiopharmaceuticals

An Improved HPLC Separation Method for TSPO Radioligand [¹¹C]ER176 Clinical Production

Article

Author: Li, Kang‐Po ; Cai, Hancheng

ABSTRACTMitochondrial membrane translocator protein 18 kDa (TSPO) expression is increased in activated microglia, established as a plausible target of neuroinflammation imaging. [11C]ER176, specifically binding to TSPO, has been developed as the third generation of radioligand for PET imaging of TSPO, which showed the potential in better quantifying neuroinflammation than its predecessors. In the current study, we developed an automated radiosynthesis with an improved HPLC purification method for [11C]ER176 clinical production. The improved HPLC separation was integrated into the automated production of [11C]ER176 using a reverse phase semi‐preparative HPLC column with an isocratic pump and the mixture of methanol and 50 mM ammonium acetate as the mobile phase. The fraction corresponding to [11C]ER176 was collected around 8.5–9.0 min without the risk of getting contaminations from nearby impurities. The automated production process took about 30 min after end of bombardment (EOB) and the quality of the final product [11C]ER176 met all specifications for clinical use based on current US Pharmacopeia and FDA CGMP requirements.

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 ; Ji, Xunming ; Zhang, Lu ; Sun, Yuli ; Yang, Tingyu ; 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.

100 Deals associated with [11C]ER-176

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Diabetic Gastroparesis	Phase 2	United States	Mayo Clinic	10 May 2021
Neuroinflammation	Phase 2	United States	Mayo Clinic	30 Mar 2021
Alzheimer Disease	Phase 2	United States	National Institute on Aging	17 Nov 2020
Amyotrophic Lateral Sclerosis	Phase 2	United States	National Institute of Mental Health	03 Jul 2019
Aphasia, Primary Progressive	Phase 2	United States	National Institute of Mental Health	03 Jul 2019
Frontotemporal Dementia	Phase 2	United States	National Institute of Mental Health	03 Jul 2019
Huntington Disease	Phase 2	United States	National Institute of Mental Health	03 Jul 2019
Inflammation	Phase 1	United States	National Institute of Mental Health	14 Jun 2019
Myositis	Phase 1	United States	National Institute of Mental Health	14 Jun 2019
Rheumatoid Arthritis	Phase 1	United States	National Institute of Mental Health	14 Jun 2019

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03958630 (CTgov)	Phase 1	Progressive bulbar palsy \| Alzheimer Disease \| Neurodegenerative Diseases \| Frontotemporal Dementia \| Motor Neuron Disease \| Neuroinflammation \| Spastic Paraplegia 39, Autosomal Recessive \| Huntington Disease \| Dementia \| Frontotemporal Lobar Degeneration \| Amyotrophic Lateral Sclerosis \| Aphasia, Primary Progressive	13	Positron Emission Tomography (PET) Scan+11C-ER176+11C-PIB (Healthy Volunteers)	vplshxxazx(yjxktcgaaa) = hkendrxwji wlikcrbtgz (blhdwceocz, slgoeoinct - vgwvcqtkqh) View more	-	01 May 2024
				Positron Emission Tomography (PET) Scan+11C-ER176+11C-PIB (Subjects With Frontotemporal Dementia (FTD))	vplshxxazx(yjxktcgaaa) = gsiwtrcrei wlikcrbtgz (blhdwceocz, jzamggujtx - cczbxwivhn) View more
NCT03744312 (CTgov)	Phase 1/2	Alzheimer Disease \| Inflammation	9	Florbetaben+11C-ER176 (Cognitive Impairment)	dhakwtscaw(aendgwldbi) = wcipghgukm rzrcvvnzee (dtdnjneqwj, egbjqrdlkc - rvifwjqryd) View more	-	13 Sep 2023
				Florbetaben+11C-ER176 (No Cognitive Impairment)	dhakwtscaw(aendgwldbi) = zljpiwqikd rzrcvvnzee (dtdnjneqwj, stpbassquv - rwtcmpljks) View more
NCT04762719 (CTgov)	Phase 2/3	Diabetic Gastroparesis	12	Core biopsy of gastric muscle+PET/CT Scan (Diabetic Gastroparesis Subjects)	kbxpkkpfal(bgpekhpeah) = sgxgjjpjqr xvdfippiby (zglnnxiodm, ubwtivldbz - bowhhvymws) View more	-	18 Apr 2023
				PET/CT Scan (Diabetic Without Gastroparesis Subjects)	kbxpkkpfal(bgpekhpeah) = olowgdasln xvdfippiby (zglnnxiodm, shmjitezhz - drhdtotfqm) View more
SNMMI2022	Not Applicable	-	-	11C-ER176 (High-affinity binders)	pjkphfzxjg(damyhrbddc) = ICC was excellent. Variability and ICC were good even in small VOIs and PVC did not affect the results. scfyxowjme (dmzapdmhnd ) View more	-	08 Aug 2022
				11C-ER176 (Mixed-affinity binders)