Cardiovascular Toxicology, Journal Year: 2023, Volume and Issue: unknown
Published: Feb. 22, 2023
Language: Английский
Toxins, Journal Year: 2022, Volume and Issue: 14(11), P. 783 - 783
Published: Nov. 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.
Language: Английский
Citations
47
Toxins, Journal Year: 2024, Volume and Issue: 16(2), P. 71 - 71
Published: Feb. 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.
Language: Английский
Citations
10
Pharmacological Reports, Journal Year: 2023, Volume and Issue: 75(6), P. 1454 - 1473
Published: Nov. 6, 2023
Language: Английский
Citations
14
Published: Jan. 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.
Language: Английский
Citations
0
Applied Catalysis O Open, Journal Year: 2025, Volume and Issue: unknown, P. 207039 - 207039
Published: March 1, 2025
Language: Английский
Citations
0
Toxicon, Journal Year: 2023, Volume and Issue: 230, P. 107152 - 107152
Published: May 11, 2023
Language: Английский
Citations
9
Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Journal Year: 2023, Volume and Issue: 1872(2), P. 140992 - 140992
Published: Dec. 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.
Language: Английский
Citations
8
Toxicon, Journal Year: 2024, Volume and Issue: 241, P. 107680 - 107680
Published: March 5, 2024
Language: Английский
Citations
2
Toxicon, Journal Year: 2023, Volume and Issue: 234, P. 107288 - 107288
Published: Sept. 12, 2023
Language: Английский
Citations
6
Toxicon, Journal Year: 2022, Volume and Issue: 214, P. 54 - 61
Published: May 14, 2022
Language: Английский
Citations
8