Cardiovascular Toxicology, Год журнала: 2023, Номер unknown
Опубликована: Фев. 22, 2023
Язык: Английский
Toxins, Год журнала: 2022, Номер 14(11), С. 783 - 783
Опубликована: Ноя. 11, 2022
The availability of effective, reliably accessible, and affordable treatments for snakebite envenoming is a critical long unmet medical need. Recently, small, synthetic toxin-specific inhibitors with oral bioavailability used in conjunction antivenom have been identified as having the potential to greatly improve outcomes after snakebite. Varespladib, molecule that broadly potently inhibits secreted phospholipase A2 (sPLA2s) venom toxins has renewed interest this class due its utility treatment envenoming. development varespladib dosage form, varespladib-methyl, accelerated by previous clinical campaigns treat non-envenoming conditions related ulcerative colitis, rheumatoid arthritis, asthma, sepsis, acute coronary syndrome. To date, twenty-nine studies evaluating safety, pharmacokinetics (PK), efficacy non-snakebite completed more than 4600 human subjects, drugs were generally well-tolerated considered safe use humans. Since 2016, 30 publications describing structure, function, directly addressed This review summarizes preclinical findings outlines scientific support, limitations, next steps varespladib's treatment, which now Phase 2 trials United States India.
Язык: Английский
Процитировано
48
Toxins, Год журнала: 2024, Номер 16(2), С. 71 - 71
Опубликована: Фев. 1, 2024
Viper venom phospholipase A2 enzymes (vvPLA2s) and A2-like (PLA2-like) proteins are two of the principal toxins in viper that responsible for severe myotoxic neurotoxic effects caused by snakebite envenoming, among other pathologies. As envenoming is deadliest neglected tropical disease, a complete understanding these proteins’ properties their mechanisms action urgently needed. Therefore, we created database comprising information on holo-form, cofactor-bound 3D structure 217 vvPLA2 PLA2-like physiologic environment, as well 79 membrane-bound species from 24 genera, which have made available to scientific community accelerate development new anti-snakebite drugs. In addition, analysis sequenced, reveals essential aspects anatomy proteins, toxicity mechanisms, conserved binding site areas may anchor universal interspecific inhibitors. Moreover, it pinpoints hypotheses molecular origin myotoxicity proteins. Altogether, this study provides an diversity how they conserved, indicates develop broad, interspecies, efficient small-molecule inhibitors target toxin’s many action.
Язык: Английский
Процитировано
11
Pharmacological Reports, Год журнала: 2023, Номер 75(6), С. 1454 - 1473
Опубликована: Ноя. 6, 2023
Язык: Английский
Процитировано
16
Toxicon, Год журнала: 2023, Номер 230, С. 107152 - 107152
Опубликована: Май 11, 2023
Язык: Английский
Процитировано
9
Опубликована: Янв. 1, 2025
The α-ketoamides are essential building blocks for the synthesis of β-lactams and oxazolidinones. As it contains multiple reactive centers, could be a suitable starting material following reactions such as Michael addition reaction, Pictet–Spengler Mannich, Stetter reaction etc. There many US FDA approved drug molecules which bear α-ketoamide moieties, boceprevir, telaprevir, fostemsavir, varespladib Copper-catalyzed from aryl methyl ketones, acetic acids, alkynes, acetaldehydes, α-keto α-azido 1,3-diketo compounds have been reported. This review describes research articles (since year 2012) related copper-catalyzed mechanism those reactions.
Язык: Английский
Процитировано
0
Applied Catalysis O Open, Год журнала: 2025, Номер unknown, С. 207039 - 207039
Опубликована: Март 1, 2025
Язык: Английский
Процитировано
0
Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Год журнала: 2023, Номер 1872(2), С. 140992 - 140992
Опубликована: Дек. 27, 2023
Snake venoms consist of highly biologically active proteins and peptides that are responsible for the lethal physiological effects snakebite envenomation. In order to guide development targeted antivenom strategies, comprehensive understanding venom compositions in-depth characterisation various proteoforms, often not captured by traditional bottom-up proteomic workflows, is necessary. Here, we employ an integrated 'omics' intact mass spectrometry (MS)-based approach profile heterogeneity within forest cobra (Naja melanoleuca), adopting different analytical strategies accommodate dynamic molecular range present. The proteome N. melanoleuca was catalogued using a gland transcriptome-guided proteomics approach, revealing consisting six toxin superfamilies. subtle diversity present in components further explored reversed phase-ultra performance liquid chromatography (RP-UPLC) coupled MS. This showed significant increase number proteoforms families were previous studies. Furthermore, probed at higher-order structures larger combination native MS photometry revealed structural along with extensive post-translational modifications form glycosylation these toxins. show diverse snake workflow incorporates proteoform level, complementing approaches.
Язык: Английский
Процитировано
8
Toxicon, Год журнала: 2023, Номер 234, С. 107288 - 107288
Опубликована: Сен. 12, 2023
Язык: Английский
Процитировано
7
Toxicon, Год журнала: 2024, Номер 241, С. 107680 - 107680
Опубликована: Март 5, 2024
Язык: Английский
Процитировано
2
Toxicon, Год журнала: 2022, Номер 214, С. 54 - 61
Опубликована: Май 14, 2022
Язык: Английский
Процитировано
8