A patent review of transient receptor potential vanilloid type 1 modulators (2014–present)

Gao, Mengkang; Wang, Yusui; Liu, Lanqi; Qiao, Zhenrui; Yang, Lin

doi:10.1080/13543776.2021.1854225

Cited by 22 publications

(8 citation statements)

References 33 publications

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“…The three‐segment structure of typical TRPV1 modulators includes a head segment containing aromatic groups; a neck segment with a connecting group of urea, thiourea, ester group, or amide group; and a lipophilic tail segment (Gao et al, 2021; Szallasi et al, 2007). This structure feature is determined by the unique pocket, and three hits also have this structure.…”

Section: Discussionmentioning

confidence: 99%

Discovery of novel TRPV1 modulators through machine learning‐based molecular docking and molecular similarity searching

Wei¹,

Yang²,

Yang³

et al. 2023

Chem Biol Drug Des

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The transient receptor potential vanilloid 1 (TRPV1) channel belongs to the transient receptor potential channel superfamily and participates in many physiological processes. TRPV1 modulators (both agonists and antagonists) can effectively inhibit pain caused by various factors and have curative effects in various diseases, such as itch, cancer, and cardiovascular diseases. Therefore, the development of TRPV1 channel modulators is of great importance. In this study, the structure‐based virtual screening and ligand‐based virtual screening methods were used to screen compound databases respectively. In the structure‐based virtual screening route, a full‐length human TRPV1 protein was first constructed, three molecular docking methods with different precisions were performed based on the hTRPV1 structure, and a machine learning‐based rescoring model by the XGBoost algorithm was constructed to enrich active compounds. In the ligand‐based virtual screening route, the ROCS program was used for 3D shape similarity searching and the EON program was used for electrostatic similarity searching. Final 77 compounds were selected from two routes for in vitro assays. The results showed that 8 of them were identified as active compounds, including three hits with IC50 values close to capsazepine. In addition, one hit is a partial agonist with both agonistic and antagonistic activity. The mechanisms of some active compounds were investigated by molecular dynamics simulation, which explained their agonism or antagonism.

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Section: Discussionmentioning

confidence: 99%

Discovery of novel TRPV1 modulators through machine learning‐based molecular docking and molecular similarity searching

Wei¹,

Yang²,

Yang³

et al. 2023

Chem Biol Drug Des

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show abstract

“…These efferents convey nociceptive information into the central nervous system. The role of these neurons in pain sensation, and the efforts to develop clinically useful analgesic agents that block the capsaicin receptor TRPV1, were detailed elsewhere [ 122 , 123 , 124 ]. Here it suffices to mention that the initial excitation by capsaicin of these neurons is followed by a lasting refractory state, traditionally termed “desensitization” [ 4 , 68 ].…”

Section: Capsaicin-sensitive Nerves and Obesitymentioning

confidence: 99%

“…Fourth, small molecule TRPV1 antagonists are potential analgesic [ 122 , 123 , 124 ] and antidiabetic [ 111 ] drugs. Some of these compounds have already entered Phase-3 clinical trials.…”

Section: Future Directionsmentioning

confidence: 99%

Capsaicin for Weight Control: “Exercise in a Pill” (or Just Another Fad)?

Szállaśi

2022

Pharmaceuticals

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Medical management of obesity represents a large unmet clinical need. Animal experiments suggest a therapeutic potential for dietary capsaicin, the pungent ingredient in hot chili peppers, to lose weight. This is an attractive theory since capsaicin has been a culinary staple for thousands of years and is generally deemed safe when consumed in hedonically acceptable, restaurant-like doses. This review critically evaluates the available experimental and clinical evidence for and against capsaicin as a weight control agent and comes to the conclusion that capsaicin is not a magic “exercise in a pill”, although there is emerging evidence that it may help restore a healthy gut microbiota.

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“…Small molecule TRPV1 antagonists are potential analgesic, antitussive, and antiphlogistic drugs [ 181 , 182 , 183 ]. A number of TRPV1 antagonists have already entered Phase-3 clinical trials for these clinical indications [ 180 ].…”

Section: Future Directionsmentioning

confidence: 99%

Dietary Capsaicin: A Spicy Way to Improve Cardio-Metabolic Health?

Szállaśi

2022

Biomolecules

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Today’s sedentary lifestyle with too much food and too little exercise has made metabolic syndrome a pandemic. Metabolic syndrome is a major risk factor for type-2 diabetes and cardiovascular disease. New knowledge of medical and nutraceutical intervention in the early stages of metabolic syndrome is central to prevent these deadly complications. People who eat chili pepper on a regular basis seem to stay healthier and live longer than those who do not. Animal experiments suggest a therapeutic potential for dietary capsaicin, the active principle in hot chili pepper, to reduce the risk of developing metabolic syndrome. This is an attractive theory since capsaicin has been a culinary staple for thousands of years, and is generally deemed safe when consumed in hedonically acceptable doses. The broad expression of the capsaicin receptor TRPV1 in metabolically active tissues lends experimental support to this theory. This review critically evaluates the available experimental and clinical evidence for and against dietary capsaicin being an effective dietary means to improve cardio-metabolic health. It comes to the conclusion that although a chili pepper-rich diet is associated with a reduced risk of dying due to cardiovascular disease, dietary capsaicin has no clear effect on blood glucose or lipid profiles. Therefore, the reduced mortality risk may reflect the beneficial action of digested capsaicin on gut microbiota.

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A patent review of transient receptor potential vanilloid type 1 modulators (2014–present)

Cited by 22 publications

References 33 publications

Discovery of novel TRPV1 modulators through machine learning‐based molecular docking and molecular similarity searching

Discovery of novel TRPV1 modulators through machine learning‐based molecular docking and molecular similarity searching

Capsaicin for Weight Control: “Exercise in a Pill” (or Just Another Fad)?

Dietary Capsaicin: A Spicy Way to Improve Cardio-Metabolic Health?

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