'Ephelia'

Mulvihill, Maureen E.

doi:10.4324/9781315256221

Cited by 2 publications

(2 citation statements)

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“…19 Considering its prime role in 2-AG hydrolysis in the brain, selective inhibition of MAGL may represent an alternative and potential therapeutic target for treatment of diverse pathological conditions including chronic pain, inflammation, cancer and neurodegeneration without apparent side effects related with direct CB 1 regulation. [20][21][22][23][24][25][26][27][28][29][30][31] Positron emission tomography (PET) is a non-invasive and highly sensitive technology in the realm of molecular imaging, and serves as an ideal tool to quantify biochemical and pharmacological processes in vivo under normal and disease conditions. [32][33][34] PET studies of MAGL would allow to achieve in-depth knowledge of MAGL-related pathological changes between normal and disease state, and in vivo interaction of novel MAGL inhibitors with the target.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Evaluation of Reversible and Irreversible Monoacylglycerol Lipase Positron Emission Tomography (PET) Tracers Using a “Tail Switching” Strategy on a Piperazinyl Azetidine Skeleton

et al. 2019

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Monoacylglycerol lipase (MAGL) is a serine hydrolase that degrades 2-arachidonoylglycerol (2-AG) in the endocannabinoid system (eCB). Selective inhibition of MAGL has emerged as a potential therapeutic approach for the treatment of diverse pathological conditions including chronic pain, inflammation, cancer and neurodegeneration. Herein we disclose a novel array of reversible and irreversible MAGL inhibitors by means of tail switching on a piperazinyl azetidine scaffold. We developed a lead irreversible-binding MAGL inhibitor 8, and reversible-binding compounds 17 and 37 which are amenable for radiolabeling with 11 C or 18 F. [ 11 C]8 ([ 11 C]MAGL-2-11) exhibited high brain uptake and excellent binding specificity in the brain towards MAGL. Reversible radioligands [ 11 C]17 ([ 11 C]PAD) and [ 18 F]37 ([ 18 F]MAGL-4-11) also demonstrated excellent in vivo binding specificity towards MAGL in peripheral organs. This work may pave the way for the development of MAGL-targeted positron emission tomography (PET) tracers with tunability in reversible and irreversible binding mechanism.

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Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Evaluation of Reversible and Irreversible Monoacylglycerol Lipase Positron Emission Tomography (PET) Tracers Using a “Tail Switching” Strategy on a Piperazinyl Azetidine Skeleton

et al. 2019

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“…We retrieved 68 CD47 small molecule inhibitors from Reaxys (Levy, 2014), Cortellis (Mulvihill, 2012) and BindingDB (Liu et al, 2007), among which, 2 CD47 small molecule inhibitors have activities (IC 50 or binding affinity) of less than 1 µM. The activities and structures of the 2 known most active small molecule inhibitors are shown in Table 2.…”

Section: Application To Screen New Cd47 Inhibitors 221 Preparation Of...mentioning

confidence: 99%

GcForest-based compound-protein interaction prediction model and its application in discovering small-molecule drugs targeting CD47

Shan,

Chen,

et al. 2023

Front. Chem.

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Identifying compound–protein interaction plays a vital role in drug discovery. Artificial intelligence (AI), especially machine learning (ML) and deep learning (DL) algorithms, are playing increasingly important roles in compound-protein interaction (CPI) prediction. However, ML relies on learning from large sample data. And the CPI for specific target often has a small amount of data available. To overcome the dilemma, we propose a virtual screening model, in which word2vec is used as an embedding tool to generate low-dimensional vectors of SMILES of compounds and amino acid sequences of proteins, and the modified multi-grained cascade forest based gcForest is used as the classifier. This proposed method is capable of constructing a model from raw data, adjusting model complexity according to the scale of datasets, especially for small scale datasets, and is robust with few hyper-parameters and without over-fitting. We found that the proposed model is superior to other CPI prediction models and performs well on the constructed challenging dataset. We finally predicted 2 new inhibitors for clusters of differentiation 47(CD47) which has few known inhibitors. The IC50s of enzyme activities of these 2 new small molecular inhibitors targeting CD47-SIRPα interaction are 3.57 and 4.79 μM respectively. These results fully demonstrate the competence of this concise but efficient tool for CPI prediction.

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'Ephelia'

Cited by 2 publications

References 0 publications

Design, Synthesis, and Evaluation of Reversible and Irreversible Monoacylglycerol Lipase Positron Emission Tomography (PET) Tracers Using a “Tail Switching” Strategy on a Piperazinyl Azetidine Skeleton

Design, Synthesis, and Evaluation of Reversible and Irreversible Monoacylglycerol Lipase Positron Emission Tomography (PET) Tracers Using a “Tail Switching” Strategy on a Piperazinyl Azetidine Skeleton

GcForest-based compound-protein interaction prediction model and its application in discovering small-molecule drugs targeting CD47

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