作者: Hibbs, David E. ; Brooker, Lance ; Glass, Michelle ; Goebel, Catrin ; Banister, Samuel D. ; Kassiou, Michael ; Longworth, Mitchell ; English, Katrina ; McGregor, Iain S. ; Stuart, Jordyn ; Apetz, Nadine ; Connor, Mark ; Wilkinson, Shane M.

Two novel adamantane derivatives, adamantan-1-yl(1-pentyl-1H-indol-3-yl)methanone (AB-001) and N-(adamtan-1-yl)-1-pentyl-1H-indole-3-carboxamide (SDB-001), were recently identified as cannabimimetic indoles of abuse. Conflicting anecdotal reports of the psychoactivity of AB-001 in humans, and a complete dearth of information about the bioactivity of SDB-001, prompted the preparation of AB-001, SDB-001, and several analogues intended to explore preliminary structure-activity relationships within this class. This study sought to elucidate which structural features of AB-001, SDB-001, and their analogues govern the cannabimimetic potency of these chemotypes in vitro and in vivo. All compounds showed similar full agonist profiles at CB1 (EC50 = 16-43 nM) and CB2 (EC50 = 29-216 nM) receptors in vitro using a FLIPR membrane potential assay, with the exception of SDB-002, which demonstrated partial agonist activity at CB2 receptors. The activity of AB-001, AB-002, and SDB-001 in rats was compared to that of Δ(9)-tetrahydrocannabinol (Δ(9)-THC) and cannabimimetic indole JWH-018 using biotelemetry. SDB-001 dose-dependently induced hypothermia and reduced heart rate (maximal dose 10 mg/kg) with potency comparable to that of Δ(9)-tetrahydrocannabinol (Δ(9)-THC, maximal dose 10 mg/kg), and lower than that of JWH-018 (maximal dose 3 mg/kg). Additionally, the changes in body temperature and heart rate affected by SDB-001 are of longer duration than those of Δ(9)-THC or JWH-018, suggesting a different pharmacokinetic profile. In contrast, AB-001, and its homologue, AB-002, did not produce significant hypothermic and bradycardic effects, even at relatively higher doses (up to 30 mg/kg), indicating greatly reduced potency compared to Δ(9)-THC, JWH-018, and SDB-001.

项与 AB-002 (Nanjing Aubrak) 相关的新闻（医药）

2023-05-17

·PRNewswire

ImmunoBrain Checkpoint Doses First Patients in Phase 1b Clinical Trial of IBC-Ab002 for Alzheimer's Disease

First human subjects have been treated with ImmunoBrain Checkpoint's novel anti-PD-L1 antibody, IBC-Ab002, in the Phase 1b IBC-01-01 clinical trial NEW YORK, May 17, 2023 /PRNewswire/ -- ImmunoBrain Checkpoint Inc. (IBC), a biopharmaceutical company developing innovative disease-modifying immune therapies to combat neurodegenerative diseases, today announced that it has dosed the first two patients in the Phase 1b IBC-01-01 clinical trial investigating IBC's lead program, IBC-Ab002 for patients with early Alzheimer's disease. IBC-Ab002 is a novel, fully human anti-PD-L1 monoclonal antibody designed to harness the peripheral immune system to help the brain overcome the multiple pathological factors that contribute to the cognitive manifestation and progression of neurodegenerative diseases, including local brain inflammation, amyloid beta, tau pathologies and neuronal loss. "The initiation of our IBC-01-01 clinical investigation represents a significant milestone, not only for IBC but for the transformed understanding of brain-immune relationships," said Professor Michal Schwartz, Ph.D., co-founder and Chief Scientific Officer of IBC. "After decades investigating the role of the immune system in brain aging and neurodegenerative disease, it is very exciting to advance this research into the clinic. New approaches to treating early and later stage Alzheimer's disease are urgently needed; our preclinical data suggests that controlled activation of the peripheral immune system can contain brain neuroinflammation and lead to disease modification." "Alzheimer's disease represents a significant unmet medical need as current therapeutic options show limited benefits. We are excited about the clinical potential of IBC-Ab002, as it represents a truly novel and innovative therapeutic approach in the neurodegenerative disease space," said Robert L. Glanzman, M.D., Chief Medical Officer of IBC. "We look forward to pursuing this promising approach to benefit people living with Alzheimer's disease and their loved ones." "Our successful recruitment of the first two patients brings us closer to revealing the therapeutic potential of immunotherapy in this vital area of research," said Catherine Mummery, M.D., the principal investigator of the study and the head of clinical trials at the Dementia Research Centre, University College London. IBC-01-01 [NCT05551741] is a randomized, double-blind, placebo-controlled, first-in-human Phase 1b clinical trial designed to evaluate safety, tolerability, pharmacokinetics and exploratory markers of efficacy of IBC-Ab002 in patients with early Alzheimer's disease. The study features single and multiple ascending doses, administered intravenously across up to five cohorts, with a 3:1 patient randomization for IBC-Ab002 or placebo. Conducted in Israel, the UK, and the Netherlands, IBC plans to enroll 40 participants. About ImmunoBrain Checkpoint ImmunoBrain Checkpoint (IBC) is a biopharmaceutical company developing novel immune therapies to combat neurodegenerative diseases. Established in 2015, IBC builds on over 20 years of research by Professor Michal Schwartz's team at the Weizmann Institute of Science, which pioneered the concept that the brain relies on the immune system for maintenance and repair, with this communication compromised in aging and Alzheimer's disease. This research led to the development of IBC-Ab002, an antibody that targets an inhibitory immune checkpoint to rewire brain/immune communication and protect the brain from functional loss. The company is currently investigating IBC-Ab002 in the IBC-01-01 clinical trial for Alzheimer's disease [NCT05551741], which is supported in part by grants from the National Institute on Aging (NIA) and the Alzheimer's Association. For more information, visit About IBC-Ab002 IBC-Ab002 is a proprietary anti-PD-L1 antibody, developed by IBC for the treatment of Alzheimer's disease. Pre-clinical studies found that in various animal models of dementia, transient activation of the peripheral immune system, achieved through immune checkpoint blockade, can reduce local brain inflammation and reduce the accumulation of toxic pathological proteins (both tau and amyloid) within the diseased brain. This results in an overall neuroprotective effect, and a slowing of cognitive decline. Optimized for this novel mechanism of action, IBC-Ab002 is administered once every three months and has a short half-life that allows for transient inhibition of the PD-L1 immune checkpoint pathway. These advantageous features may improve the investigational antibody's safety profile. Disclaimer: Research reported in this press release is supported by the National Institutes of Health's National Institute on Aging, Award Number R01AG071810. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Contact Corporate Inquiries [email protected] SOURCE ImmunoBrain Checkpoint Inc.

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100 项与 AB-002 (Nanjing Aubrak) 相关的药物交易

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