A Multicenter, Open Label Study to Evaluate Tolerability and Efficacy of Orally Administered ENT-01 for the Treatment of Parkinson's Disease Dementia.

This study will be conducted as a multi-center, open label study in the US. There will be 40 patient to receive the active investigational product.

开始日期2024-03-01

申办/合作机构

Enterin, Inc.

NCT04483479

/ Terminated临床2期

A Multicenter, Non-Randomized, Open-Label Study to Evaluate the Safety and Efficacy of Orally Administered ENT-01 in Improving Constipation and Neurologic Symptoms in Patients With Parkinson's Disease and Constipation Over a 14-week Period

This study will be conducted as an open-label safety follow-on to a multi-center, double-blind, randomized study. All subjects who participated in the randomized study will be offered participation in this unblinded, single-arm, safety study. Approximately 50 subjects will be entered into the study and ENT-01 will be administered daily in escalating doses followed by a fixed dose for 12 weeks. Each subject will participate for approximately 20 weeks; dosing duration will be approximately 14 weeks.

开始日期2020-07-30

申办/合作机构

Enterin, Inc.

NCT03781791

/ Completed临床2期

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Study to Evaluate Safety, Tolerability and Efficacy of Orally Administered ENT-01 for the Treatment of Parkinson's Disease-Related Constipation (KARMET)

This study will be conducted as a multi-center, randomized, double-blind, placebo-controlled study. Approximately 72 patients will be randomized 3:1 to treatment or placebo, with approximately 54 patients allocated to receive the active investigational product and approximately 18 patients allocated to receive placebo.
- Study Update-
Amendment 3 - In this amendment, an additional 80 patients (approximately) will be randomized 1:1 to treatment or placebo (double-blind) with approximately 40 subjects allocated to each group.

开始日期2018-12-10

申办/合作机构

Enterin, Inc.

100 项与 Kenterin 相关的临床结果

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100 项与 Kenterin 相关的转化医学

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133

项与 Kenterin 相关的文献（医药）

2025-02-13·JOURNAL OF PHYSICAL CHEMISTRY B

Interaction of Squalamine with Lipid Membranes

Article

作者: Ulrich, Anne S. ; Afonin, Sergii ; Kohlmeyer, Annika ; Meng, Beibei ; Guschtschin-Schmidt, Nadja ; Grage, Stephan L.

Squalamine is an aminosterol from dogfish shark which has drawn attention, besides its antimicrobial activity, as a drug candidate in the treatment of Parkinson's disease due to its ability to prevent binding of α-synuclein to lipid membranes. To get insight into the mode of action of this steroid, we studied the influence of squalamine on lipid bilayers and whether it could inhibit the binding of a model peptide. Solid-state ¹⁹F NMR of labeled [KIGAKI]₃ indicated that, indeed, this peptide no longer binds as a flexible chain to the bilayer in the presence of squalamine. When the cationic squalamine was added to lipid vesicles containing phosphatidylglycerol lipids, the aminosterol was found in differential scanning calorimetry and solid-state ³¹P NMR experiments to lower the gel-to-fluid phase transition and cause the phase separation of domains enriched in anionic lipids. Squalamine had only a little influence on ²H NMR relaxation and on the order parameters of the chains. These findings indicate that the aminosterol does not affect the molecular mobility of the hydrophobic core of the bilayer; hence, it does not insert into the membrane, nor causes thinning as found for molecules inserting in the headgroup region. On the other hand, squalamine was found to interact with lipid headgroups through electrostatic interactions, as seen by solid-state ²H NMR on headgroup-labeled lipids. Furthermore, ³¹P NMR showed that squalamine shifted the lamellar-to-hexagonal phase transition of phosphatidylethanolamine lipids to higher temperatures, indicating a preference for positively curved membranes. Altogether, our experiments indicate a strong interaction of the cationic squalamine with lipid headgroups, in particular with anionic lipids. This affinity for membranes is strong enough to efficiently displace cationic polypeptides, confirming the proposed action mechanism in Parkinson treatment. Notably, supported by ¹H-¹H NOESY experiments, it was found that squalamine does not insert into the bilayer, but rather acts as facial amphiphile binding to the membrane surface. The binding to membranes may be envisaged in the form of oligomeric or micellar assemblies, which can disrupt the membrane at high concentrations, thereby explaining the antimicrobial and antifungal activities of squalamine.

2025-01-10·ACS Infectious Diseases

High-Throughput Screening of More Than 30,000 Compounds for Anthelmintics against Gastrointestinal Nematode Parasites

Article

作者: Thompson, Paul R. ; Chen, Paulina ; Barasa, Leonard ; Kim, Youmie ; Aroian, Raffi V. ; Elfawal, Mostafa A. ; Goetz, Emily ; Savinov, Sergey N.

Gastrointestinal nematodes (GINs) are among the most common parasites of humans, livestock, and companion animals. GIN parasites infect 1-2 billion people worldwide, significantly impacting hundreds of millions of children, pregnant women, and adult workers, thereby perpetuating poverty. Two benzimidazoles with suboptimal efficacy are currently used to treat GINs in humans as part of mass drug administrations, with many instances of lower-than-expected or poor efficacy and possible resistance. Thus, new anthelmintics are urgently needed. However, screening methods for new anthelmintics using human GINs typically have low throughput. Here, using our novel screening pipeline that starts with human hookworms, we screened 30,238 unique small molecules from a wide range of compound libraries, including ones with generic diversity, repurposed drugs, natural derivatives, known mechanisms of action, as well as multiple target-focused libraries (e.g., targeting kinases, GPCRs, and neuronal proteins). We identified 55 compounds with broad-spectrum activity against adult stages of two evolutionary divergent GINs, hookworms (Ancylostoma ceylanicum) and whipworms (Trichuris muris). Based on known databases, the targets of these 55 compounds were predicted in nematode parasites. One novel scaffold from the diversity set library, F0317-0202, showed good activity (high motility inhibition) against both GINs. To better understand this novel scaffold's structure-activity relationships (SAR), we screened 28 analogs and created SAR models highlighting chemical and functional groups required for broad-spectrum activity. These studies validate our new and efficient screening pipeline at the level of tens of thousands of compounds and provide an important set of new GIN-active compounds for developing novel and broadly active anthelmintics.

2024-10-01·EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Natural products targeting amyloid-β oligomer neurotoxicity in Alzheimer's disease

Review

作者: Cordeiro, Yraima ; Gonçalves, Priscila Baltazar ; Sodero, Ana Carolina Rennó

Alzheimer's disease (AD) constitutes a major global health issue, characterized by progressive neurodegeneration and cognitive impairment, for which no curative treatment is currently available. Current therapeutic approaches are focused on symptom management, highlighting the critical need for disease-modifying therapy. The hallmark pathology of AD involves the aggregation and accumulation of amyloid-β (Aβ) peptides in the brain. Consequently, drug discovery efforts in recent decades have centered on the Aβ aggregation cascade, which includes the transition of monomeric Aβ peptides into toxic oligomers and, ultimately, mature fibrils. Historically, anti-Aβ strategies focused on the clearance of amyloid fibrils using monoclonal antibodies. However, substantial evidence has highlighted the critical role of Aβ oligomers (AβOs) in AD pathogenesis. Soluble AβOs are now recognized as more toxic than fibrils, directly contributing to synaptic impairment, neuronal damage, and the onset of AD. Targeting AβOs has emerged as a promising therapeutic approach to mitigate cognitive decline in AD. Natural products (NPs) have demonstrated promise against AβO neurotoxicity through various mechanisms, including preventing AβO formation, enhancing clearance mechanisms, or converting AβOs into non-toxic species. Understanding the mechanisms by which anti-AβO NPs operate is useful for developing disease-modifying treatments for AD. In this review, we explore the role of NPs in mitigating AβO neurotoxicity for AD drug discovery, summarizing key evidence from biophysical methods, cellular assays, and animal models. By discussing how NPs modulate AβO neurotoxicity across various experimental systems, we aim to provide valuable insights into novel therapeutic strategies targeting AβOs in AD.

项与 Kenterin 相关的新闻（医药）

2023-06-24

·GlobeNewswire-Health Care

Enterin Presents Data Demonstrating Strong Benefit of ENT-03 on Body Weight, Adiposity and Blood Glucose Vs. Semaglutide in a Diet Induced Obesity Mouse Model

Data presented at the American Diabetes Association 83rd Scientific SessionsPHILADELPHIA, June 24, 2023 (GLOBE NEWSWIRE) -- Enterin Inc., a privately held, Philadelphia-based, clinical-stage biopharmaceutical company pioneering novel treatments for neurodegenerative and metabolic diseases, presented in vivo data demonstrating benefit on body weight, adiposity and blood glucose of ENT-03 compared to semaglutide in an obese, diabetic animal model, with persistence of benefit on weight beyond treatment. The data were presented at the American Diabetes Association’s (ADA) 83rd Scientific Sessions in San Diego. “ENT-03 differs profoundly from the GLP-1 agonists both with respect to its pharmacology and mechanism of action,” said Michael Zasloff, M.D., Ph.D., Scientific Director of the Medstar Georgetown Transplant Institute, Co-Founder and Chief Scientific Officer of Enterin and senior author of the paper. “We believe ENT-03 can add a new dimension to the management of Type 2 diabetes and obesity.” ENT-03 is a novel, endogenous, centrally acting mammalian aminosterol with Protein Tyrosine Phosphatase 1B (PTP1B) inhibitory activity, which normalizes glucose and causes weight loss by acting on brain circuits that regulate energy and metabolism. In obese, diabetic mice, ENT-03 rapidly lowers blood glucose, reduces food intake and adiposity, eliminates liver fat, and improves liver function. The study presented today compared the effects of subcutaneously administered ENT-03 to semaglutide on blood glucose, adiposity, and body weight over a 10-week treatment period in a diet-induced obesity (DIO) mouse model. Within one-to-two weeks of treatment with ENT-03, DIO mice exhibit a rapid and substantial fall in blood glucose, out of proportion to the loss of weight. In contrast, in semaglutide treated DIO mice, glucose falls in proportion to weight loss. Weight loss continues smoothly in the ENT-03 treatment group over the 10-week period, plateauing at lean body weight, and blood glucose remains in the normoglycemic range. In contrast, the effects of semaglutide on both weight loss and blood glucose begin to diminish between four and six weeks after initiation of treatment, since both body weight and blood glucose increase despite continued dosing. Within several days following the end of the 10-week treatment period, the semaglutide group exhibited a sharp rebound in food intake and body weight and by five weeks approached the body weight of the untreated obese mice. In contrast, ENT-03 treated animals maintained the lower weight and the reduced food intake, with no evidence of rebound in either. Body fat, which decreased significantly in both groups during treatment, increased at a faster rate in the semaglutide group post-treatment compared with the ENT-03 group. Results can be found online at www.enterininc.com and at https://diabetesjournals.org/diabetes/article/72/Supplement_1/854-P/149928/854-P-ENT-03-a-Centrally-Acting-Endogenous. “Weight loss during treatment with ENT-03 is progressive, profound and outlasts the treatment period for prolonged periods, which suggests that a neuroregenerative process might be taking place,” said Denise Barbut, M.D., F.R.C.P., Co-Founder, President, and Chief Medical Officer of Enterin and first author of the paper. Phase 1 studies in obese and diabetic subjects are currently in progress (IND155001). Results of the first-in-human, randomized, double-blind, single ascending dose study involving approximately 49 subjects with obesity with or without Type 2 diabetes are expected to be available in the fourth quarter of 2023. ENT-03 is Enterin’s second compound in clinical trials. The first compound, ENT-01, has completed a successful randomized Phase 2b study in patients with Parkinson’s disease (https://www.acpjournals.org/doi/10.7326/M22-1438). About Enterin Inc. Enterin Inc. is the first company to develop novel compounds that repair the dysfunctional gut-brain axis in patients with neurodegenerative diseases. Enterin Inc. is pioneering the medical community’s understanding of the link between infections, dysfunction of the enteric nervous system (ENS) and the onset and progression of neurodegenerative disease. Enterin’s lead compound, ENT-01, displaces membrane-bound alpha-synuclein (αS) aggregates from nerve cells in the ENS and improves neural signalling between the gut and the brain. Enterin Inc. has completed a large, randomized Phase 2b clinical trial in patients with Parkinson’s disease. The study met all the endpoints. Preparations for Phase 3 studies are currently underway. The second compound, ENT-03, increases insulin sensitivity by acting at the level of the brain. It is being developed for the treatment of diabetes, obesity, and Alzheimer’s disease. For more information, please visit www.enterininc.com. Company contact:Katherine WolfChief Financial Officerk.wolf@enterininc.com

临床2期临床结果

2023-06-05

·GlobeNewswire-Health Care

Enterin Announces the Start of a First-in-Human Study of ENT-03 in Obesity and Type 2 Diabetes

PHILADELPHIA, June 05, 2023 (GLOBE NEWSWIRE) -- Enterin Inc., a privately held, Philadelphia-based, clinical-stage biopharmaceutical company pioneering novel treatments for neurodegenerative and metabolic diseases, today announced the start of a Phase 1a study in obesity and Type 2 diabetes (IND #155001). The study is a first-in-human, single center, single dose, randomized, placebo-controlled, dose-escalating study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of subcutaneously administered ENT-03 in development for the treatment of obesity and Type 2 diabetes. It will be conducted in the U.S. and will enroll approximately 49 patients, with results expected in the fourth quarter of 2023. The first five cohorts will consist of obese but otherwise healthy volunteers and the last two cohorts will involve obese subjects with Type 2 diabetes. Each cohort will enroll five active and two placebo subjects, with a total of up to 35 subjects receiving active therapy across the seven arms and 14 subjects receiving placebo. ENT-03 is a novel, endogenous, centrally acting aminosterol with protein tyrosine phosphatase 1B (PTP1B) inhibitory activity, which normalizes glucose and causes weight loss by acting on brain circuits that regulate energy and metabolism. In obese, diabetic mice, ENT-03 rapidly normalizes blood glucose, reduces food intake and adiposity, eliminates liver fat, normalizes liver function, and increases insulin sensitivity (abstract to be presented at the American Diabetes Association, San Diego, June 25, 2023). The neural circuits affected by ENT-03 appear to differ from those impacted by semaglutide suggesting a different mechanism of action (abstract to be presented at the European Association for the Study of Diabetes, Hamburg, Germany, October 2-6, 2023). ENT-03 is Enterin’s second compound in clinical trials. The first compound, ENT-01, has completed a successful randomized Phase 2b study in patients with Parkinson’s disease (https://www.acpjournals.org/doi/10.7326/M22-1438). About Enterin Inc. Enterin Inc. is the first company to develop novel compounds that repair the dysfunctional gut-brain axis in patients with neurodegenerative diseases. The Company is pioneering the medical community’s understanding of the link between infections, dysfunction of the enteric nervous system (ENS) and the onset and progression of neurodegenerative disease. Enterin’s lead compound, ENT-01, displaces membrane-bound alpha-synuclein (αS) aggregates from nerve cells in the ENS and improves neural signaling between the gut and the brain. Enterin has completed a large, randomized Phase 2b clinical trial in patients with Parkinson’s disease. The study met all the endpoints. Preparations for Phase 3 studies are currently underway. The second compound, ENT-03, increases insulin sensitivity by acting at the level of the brain. It is being developed for the treatment of diabetes, obesity, and Alzheimer’s disease. For more information, please visit www.enterininc.com. Company contact:Katherine WolfChief Financial Officerk.wolf@enterininc.com

临床2期临床结果临床3期

2023-05-31

·BioSpace

Enterin announces FDA acceptance of an investigator sponsored IND to treat a patient with prodromal multisystem atrophy (MSA) with ENT-01

PHILADELPHIA, May 31, 2023 (GLOBE NEWSWIRE) -- Enterin Inc., a privately held, Philadelphia-based, clinical-stage biopharmaceutical company pioneering novel treatments for neurodegenerative and metabolic diseases, announces the acceptance by the U.S. Food and Drug Administration (FDA) of an investigator sponsored Investigational New Drug (IND) application (166532) to treat a patient with prodromal multisystem atrophy (MSA) with ENT-01. Treatment will continue indefinitely or until significant adverse events occur that warrant discontinuation of drug. Individuals diagnosed with MSA have an average life expectancy of 6-8 years and there is no existing treatment which halts the progression of the disease. The condition, an alpha-synucleinopathy similar to Parkinson’s disease, consists of progressive autonomic failure with prominent bowel and bladder symptoms, and central nervous system manifestations include REM-behavior disorder, dysfunctional circadian rhythm, Parkinsonism, and cognitive dysfunction. ENT-01 has been used to treat close to 200 patients with Parkinson’s disease in Phase 2a and Phase 2b (randomized) studies and dose-dependent improvement noted in the symptoms mentioned above ( ). Side effects are largely confined to the GI tract, and consist of nausea, diarrhea, and vomiting. Phase 3 studies in Parkinson’s disease-related constipation and further Phase 2 studies in Parkinson’s disease-related psychosis and dementia are being planned. The patient is a 42-year-old man with a single gene mutation (ATP13A2) which may impair lysosomal clearance mechanisms, and which predisposes to Parkinsonism and MSA. He has a 2-year history of constipation, urinary symptoms, erectile dysfunction, sleep disturbances suggestive of REM-behavior disorder, dysfunctional circadian rhythm and positive alpha-synuclein staining in duodenal enteric neurons. On the basis of these symptoms, he has been diagnosed as having prodromal MSA. ENT-01 (squalamine phosphate) acts locally on enteric neurons and electrostatically displaces misfolded, positively charged proteins such as alpha-synuclein from neuronal membranes, as well as preventing the formation and deposition of alpha-synuclein aggregates. Moreover, in preliminary experiments conducted on the patient’s own cells, ENT-01 completely prevented the oxidative stress response caused by rotenone, a highly toxic agent which impairs mitochondrial function, and which is used in animal models of PD. According to Dr. Denise Barbut, Co-Founder, President and CMO of Enterin, “This is the first time that any compound is being used to prevent the progression of MSA and a milestone in the development of ENT-01 for both treatment and prevention of other neurodegenerative disorders.” Dr. Robert Hauser, the treating physician and Director of the Parkinson’s Disease and Movement Disorders Center of the University of South Florida added, “We hope that ENT-01 will be helpful in preventing progression of MSA in this individual and that this work will help promote personalized medicine for neurodegenerative diseases.” About Enterin Inc. Enterin Inc. is the first company to develop novel compounds that repair the dysfunctional gut-brain axis in patients with neurodegenerative diseases. Enterin Inc. is pioneering the medical community’s understanding of the link between infections, dysfunction of the enteric nervous system (ENS) and the onset and progression of neurodegenerative disease. Enterin’s lead compound, ENT-01, displaces membrane-bound alpha-synuclein (αS) aggregates from nerve cells in the ENS and improves neural signalling between the gut and the brain. Enterin Inc. has completed a large, randomized Phase 2b clinical trial in patients with Parkinson’s disease. The study met all the endpoints. Preparations for Phase 3 studies are currently underway. The second compound, ENT-03, increases insulin sensitivity by acting at the level of the brain. It is being developed for the treatment of diabetes, obesity, and Alzheimer’s disease and Phase 1 clinical trials in subjects with obesity and diabetes will begin in June 2023. For more information, please visit . Enterin Inc: Katherine Wolf k.wolf@enterininc.com Investors: Lee Roth/Julia Weilman Burns McClellan lroth@burnsmc.com/jweilman@burnsmc.com Media: Selina Husain/Robert Flamm, Ph.D. Burns McClellan shusain@burnsmc.com/rflamm@burnsmc.com

临床2期临床结果临床1期

100 项与 Kenterin 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
便秘	临床2期	美国	Enterin, Inc.	2018-12-10
功能性便秘	临床2期	美国	Enterin, Inc.	2018-12-10
帕金森病	临床2期	美国	Enterin, Inc.	2018-12-10
帕金森病所致痴呆	临床1期	美国	Enterin, Inc.	2024-03-01
痴呆	临床1期	美国	Enterin, Inc.	-
精神障碍	临床1期	美国	Enterin, Inc.	-
多系统萎缩	临床申请	美国	Enterin, Inc.	2023-05-31
自闭症	临床前	美国	Enterin, Inc.	2025-04-01

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04483479 (Rollover, CTgov)	临床2期	便秘 \| 帕金森病	27	Active Investigational Treatment ENT-01	簾鹹繭壓鑰淵窪構鏇衊 = 繭顧壓齋夢壓夢願糧鏇鹹鑰遞獵鹽廠窪鏇構夢 (廠壓艱膚鬱製製壓齋製, 積膚夢夢壓觸襯構觸積 ~ 繭範鏇衊鹹選網鹹齋網) 更多	-	2024-03-19
NCT03781791 (KARMET, CTgov)	临床2期	功能性便秘 \| 便秘 \| 帕金森病	151	Active Investigational Treatment ENT-01 (Active Treatment)	鹹築醖糧鹽餘鑰觸範衊 = 夢簾鹹構淵選餘觸顧憲衊夢鏇襯襯範衊廠繭鹽 (壓繭餘憲憲選廠製廠鹽, 壓鑰構襯鹽廠範鏇夢積 ~ 糧醖夢網獵簾顧壓積鹹) 更多	-	2023-12-04
				Placebo Treatment (Placebo Treatment)	鹹築醖糧鹽餘鑰觸範衊 = 築餘鹹壓襯選獵窪範繭衊夢鏇襯襯範衊廠繭鹽 (壓繭餘憲憲選廠製廠鹽, 顧夢襯窪構選構艱醖製 ~ 鏇蓋鹽壓簾範範繭網廠) 更多
NCT03781791 (Pubmed)	临床2期	帕金森病	150	ENT-01	顧鏇鹽壓顧顧醖願構簾(築壓觸夢憲範鹹衊憲膚) = 觸獵鏇鏇夢遞憲窪鹽網鏇窪遞糧齋獵製積網糧 (遞鏇襯築淵艱糧網遞鏇 ) 更多	积极	2022-11-08
				Placebo	顧鏇鹽壓顧顧醖願構簾(築壓觸夢憲範鹹衊憲膚) = 積壓網築鹹網齋憲構網鏇窪遞糧齋獵製積網糧 (遞鏇襯築淵艱糧網遞鏇 ) 更多