A 4-Week, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study to Investigate the Safety and Efficacy of EVT 101 as Monotherapy in Patients With Treatment-Resistant Major Depression

This study is a 4-week, randomized, double-blind, parallel-group, placebo-controlled monotherapy study in patients with treatment-resistant major depression. After confirmation of treatment-resistance in a prospective treatment period with citalopram, each patient will be treated with either EVT 101 once daily or placebo for 28 consecutive days.

Start Date01 Jun 2010

Sponsor / Collaborator

Janssen Research & Development LLC

[+1]

NCT00526968 / CompletedPhase 1

A Double Blind, Placebo Controlled Study to Investigate the Role of NMDA Receptor NR2B Subunit Selective Antagonism on Cognitive Functions and Neurophysiology in Healthy Subjects as Measured With MRI

The purpose of this study is to investigate the neurophysiological changes following single doses of EVT 101 using fMRI during rest and during cognitive tasks in young healthy male subjects.

Start Date01 Sep 2007

Sponsor / Collaborator

Evotec International GmbH

[+1]

100 Clinical Results associated with EVT-101

100 Translational Medicine associated with EVT-101

100 Patents (Medical) associated with EVT-101

Literatures (Medical) associated with EVT-101

01 May 2023·European journal of medicinal chemistry

Discovery of novel tryptamine derivatives as GluN2B subunit-containing NMDA receptor antagonists via pharmacophore-merging strategy with orally available therapeutic effect of cerebral ischemia

Article

Author: He, Yeli ; Liu, Jiao ; Qin, Fengyun ; Cheng, Maosheng ; Ma, Chao ; Quan, Jishun ; Yang, Huali ; Zhao, Ying

A series of tryptamine derivatives has been designed and synthesized as novel GluN2B subunit-containing NMDA receptor (GluN2B-NMDAR) antagonists, which could simultaneously manifest the receptor-ligand interactions of representative GluN2B-NMDAR antagonists ifenprodil (1) and EVT-101 (3). In the present study, the neuroprotective potential of these compounds was explored through chemical synthesis and pharmacological characterization. Compound Z25 with significantly better neuroprotective activity than the positive control drug (percentage of protection: 55.8 ± 0.6% vs. 41.0 ± 2.7%) was considered to be an effective antagonist of the human GluN2B-NMDA receptor. Judging from in vitro pharmacological profiling, Z25 could downregulate NMDA-induced increased intracellular Ca²⁺ concentration, and Z25 could also upregulate NMDA-induced decreased intracellular p-ERK 1/2 expression, which suggested that Z25 is an antagonist of the GluN2B-NMDA receptor. Furthermore, the in vitro preliminary evaluation of the drug-like properties of compound Z25 showed remarkable plasma stability. Based on in vivo pharmacokinetic and pharmacodynamic studies in C57 mice, compound Z25 exhibited a relatively short half-life and a low F value (3.12 ± 0.01%), while administration of Z25 substantially improved the cognitive performance of mice in a series of tests of cerebral ischemic injury. Overall, these results support the further development of compound Z25 as a potential lead compound to treat the cerebral ischemic injury by antagonizing GluN2B-NMDA receptor.

24 Jul 2021·Journal of biomolecular structure & dynamics

Repurposing of cefpodoxime proxetil as potent neuroprotective agent through computational prediction and in vitro validation

Article

Author: Wang, Ying ; Ma, Chao ; Cheng, Maosheng ; Hu, Baichun ; Wang, Jian ; Quan, Jishun ; Zhang, Dongping ; Zhang, Zhuo

In recent reports, NR2B-NMDA receptor antagonists showed more research value because of its strong targeting ability and less side effects potential. In 2016, EVT-101 was reported to bind in an almost entirely new binding region of this target. Whether strikingly different binding modes can improve targeting and reduce side effects is worth studying. In our preliminary work, we explored the binding patterns of ifenprodil and EVT-101, found the key amino acids and summarized the pharmacophores, hoping to find such antagonists that target the two binding modes simultaneously. In this study, we developed a scalable virtual screening workflow in the FDA-approved drugs library to identify novel NR2B-NMDAR antagonists based on the combination of two pharmacophores. Cefpodoxime proxetil (5) was identified as the hit compound, and it was found for the first time that 5 might have neuroprotective activity as a NR2B-NMDAR antagonist. This result interested us to make further study, the ligand-receptor interactions modeled by molecular docking studies showed that the compound could perfectly merge both the pharmacophore characteristics of ifenprodil and EVT-101 at the binding cavity between the ATDs of GluN1 and GluN2B. The accuracy of molecular docking results and binding stability of ligand-receptor complexes were validated through 100 ns molecular dynamics simulation and binding free energy calculation. Afterwards, MTT assay (49.8%±0.1%, 5 μM) on NMDA injured SH-SY5Y cells and evidence of the effect on attenuating Ca²⁺ influx induced by NMDA were applied to validate the computational results, further investigation showed that 5 could suppress the NR2B upregulation induced by NMDA. [Formula: see text] Communicated by Ramaswamy H. Sarma.

01 Aug 2020·European journal of medicinal chemistryQ1 · MEDICINE

A comprehensive description of GluN2B-selective N-methyl-D-aspartate (NMDA) receptor antagonists

Q1 · MEDICINE

Review

Author: Liu, Wenwu ; Liu, Yaqian ; Ding, Huaiwei ; Sun, Xue ; Zhao, Qingchun ; Zu, Yuxin ; Yang, Yue ; Xu, Zihua ; Jiang, Xiaowen

l-glutamate is an excitatory neurotransmitter in the central nervous system (CNS), which can activate ionotropic receptors (iGluRs) and metabotropic (mGluRs) receptors. N-methyl-D-aspartate (NMDA) receptor is a ligand-gated ion channel belonging to the iGluRs family. Among NMDA receptor subtypes, GluN2B subtype plays a crucial role in CNS diseases. In this review, we summarize, classify and discuss the reports on GluN2B antagonists, published from the 1990s to 2020, to provide the therapeutic potential of GluN2B antagonists on various disorders. The GluN2B antagonists are broadly classified into two categories, which are prototypical antagonists and atypical antagonists. And the latter are further divided into amidine derivatives, 4-aminoquinolines, indole derivatives, benzimidazole derivatives, oxamide derivatives, carbamate derivatives, EVT-101 analogues, 1H-pyrrolo[3,2-b]pyridine derivatives, benzazepin derivatives, other heterocyles and radiotracers. This review will provide a comprehensive description including structure, structure-activity relationship (SAR), and pharmacology of novel GluN2B-subtype selective NMDA antagonists to the medicinal chemists, which would be helpful in rational designing effective drugs aimed toward related CNS disease.

News (Medical) associated with EVT-101

19 May 2023

·www.prnewswire.com

Endsulin Announces Passing of Founder Hans Sollinger, MD, PhD

The award-winning transplant surgeon and world leader in diabetes research revolutionized the field of transplantation through the development of a novel kidney pancreas transplant technique that significantly improved patient outcomes MADISON, Wis., May 19, 2023 /PRNewswire/ -- Endsulin announced today that Founder and Chief Scientific Officer Hans Sollinger, M.D., Ph.D., passed away peacefully on May 15, 2023, after a recurrence of a previous illness. His contributions to the field earned him numerous awards and recognitions, including the industry's highest honor, the American Society of Transplant Surgeon's distinguished Pioneer Award. At the University of Wisconsin Madison Dr. Sollinger worked tirelessly on a gene therapy approach with the potential to revolutionize the treatment of type 1 diabetes mellitus T1DM. In 2016, after 20 years of research, he founded Endsulin, an early-stage biotech company based on Dr. Sollinger's proprietary technology. Endsulin is developing a single dose, liver-directed gene therapy that enables liver cells to produce and regulate insulin, mimicking the function of the pancreas. "The passing of Hans is a profound loss," said Endsulin's Chairman of the Board and CEO, Thomas Dee. "He was a true visionary and world leader in diabetes research whose personal interest in improving diabetes care led to remarkable achievements in pancreas transplantation, the development of immunosuppression, and discovery of a gene therapy in development for T1DM. On behalf of our Board of Directors, we extend our deepest, heartfelt condolences with the Sollinger family during this difficult time. At Endsulin we will honor Hans' legacy by exhibiting his energy, passion, and ambition in everything we do to further the development of our lead candidate ENS-101, which has the potential to reach millions of patients suffering with T1D." About Endsulin Endsulin is a pre-clinical stage gene therapy company whose mission is to end insulin dependence for good and free people from being defined by diabetes. Endsulin's approach employs a widely studied and proven viral vector to deliver their patented genetic factor to the liver and restore the body's own ability to produce and regulate insulin. With a single administration, Endsulin's revolutionary genetic therapy for T1DM delivers a patented genetic factor that will "switch on" new insulin-producing cells to confer years – and perhaps a lifetime – of freedom from injecting artificial insulin, realizing the goal that has eluded researchers since the discovery of insulin. Founded by an award-winning transplant surgeon and world leader in diabetes care and supported by a team of experts in gene therapy, endocrinology, diabetes science and pharmaceutical development, Endsulin has the scientific, medical, and commercial expertise to develop its innovative therapy quickly, filling an enormous unmet need and bringing us one step closer to ending insulin dependence for good — and for the good of everyone with T1DM. Media Contact: Julie Ferguson [email protected] (312)385-0098 SOURCE Endsulin

Gene TherapyExecutive Change

100 Deals associated with EVT-101

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Depressive Disorder, Treatment-Resistant	Phase 2	US	Janssen Research & Development LLC	01 Jun 2010
Depressive Disorder, Treatment-Resistant	Phase 2	US	Hoffmann-La Roche, Inc.	01 Jun 2010
Depressive Disorder, Major	Phase 2	-	Evotec SE	-
Depressive Disorder, Major	Phase 2	-	F. Hoffmann-La Roche Ltd.	-

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