Maturitas, Год журнала: 2024, Номер 186, С. 108028 - 108028
Опубликована: Май 21, 2024
Язык: Английский
ACS Medicinal Chemistry Letters, Год журнала: 2023, Номер 14(5), С. 557 - 565
Опубликована: Апрель 24, 2023
Life is constructed primarily using a toolbox of 20 canonical amino acids─relying upon these building blocks for the assembly proteins and peptides that regulate nearly every cellular task, including cell structure, function, maintenance. While Nature continues to be source inspiration drug discovery, medicinal chemists are not beholden only acids have begun explore non-canonical (ncAAs) construction designer with improved drug-like properties. However, as our ncAAs expands, hunters encountering new challenges in approaching iterative peptide design–make–test–analyze cycle seemingly boundless set blocks. This Microperspective focuses on technologies accelerating ncAA interrogation discovery (including HELM notation, late-stage functionalization, biocatalysis) while shedding light areas where further investment could accelerate medicines but also improve downstream development.
Язык: Английский
Процитировано
80
Endocrinology Diabetes & Metabolism, Год журнала: 2023, Номер 7(1)
Опубликована: Дек. 14, 2023
Abstract Background Glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) have emerged as promising therapeutic options for addressing Type‐2 diabetes, obesity, and related conditions. Among these, semaglutide, tirzepatide, liraglutide etc., all notable GLP‐1RA, gained attention owing to their favourable pharmacological properties clinical efficacy. Aims This comprehensive review aims provide a detailed analysis of both the currently available GLP‐1RAs in market those undergoing trials. The focus is on examining mechanism action, pharmacokinetics, efficacy glycemic control weight management, safety profile, potential applications. Materials & Methods employs systematic approach gather information GLP‐1RAs. Relevant literature from ongoing trials thoroughly examined. Detailed scrutiny applied understand pharmacokinetic properties, outcomes these agents. Results presents overview GLP‐1RAs, highlighting distinct mechanisms profiles, effectiveness management. Safety profiles are also discussed, providing holistic understanding Discussion findings discussed context advancements field Potential applications beyond diabetes obesity explored, shedding light broader implications agents managing Conclusion In conclusion, this underscores significance with specific management type 2 beyond. By synthesizing mechanisms, efficacy, safety, provides valuable insights into benefits offer, contributing discourse field.
Язык: Английский
Процитировано
53
Pharmacological Reviews, Год журнала: 2024, Номер 76(2), С. 267 - 299
Опубликована: Янв. 30, 2024
Type 2 diabetes mellitus (T2D) has emerged as a major global health concern that accelerated in recent years due to poor diet and lifestyle. Afflicted individuals have high blood glucose levels stem from the inability of pancreas make enough insulin meet demand. While medication can help maintain normal with chronic disease, many these medicines are outdated, severe side effects, often become less efficacious over time necessitating need for therapy. G protein-coupled receptors (GPCRs) regulate physiological processes including levels. In pancreatic β-cells, GPCRs β-cell growth, apoptosis, secretion which all critical maintaining sufficient mass output ensure euglycemia. years, new insight into signaling incretin other underscored potential desirable targets treatment diabetes. The is modulated by GPCR kinases (GRKs) phosphorylate agonist activated marking receptor arrestin binding internalization. Interestingly, genome wide association studies (GWAS) using diabetic patient cohorts link GRKs arrestins T2D. Moreover, reports show expressed serve role regulation function growth both dependent independent pathways. this review, we describe importance GRK modulating physiology. Significance Statement Pancreatic β-cells contain diverse array been shown improve survival, yet only handful successfully targeted This review discusses advances our understanding pharmacology while also highlighting necessity investigating islet enriched largely unexplored unveil novel strategies.
Язык: Английский
Процитировано
21
Molecules, Год журнала: 2022, Номер 27(21), С. 7232 - 7232
Опубликована: Окт. 25, 2022
Cancer remains the leading cause of death worldwide despite advances in treatment options for patients. As such, safe and effective therapeutics are required. Short peptides provide advantages to be used cancer management due their unique properties, amazing versatility, progress biotechnology overcome peptide limitations. Several appealing peptide-based therapeutic strategies have been developed. Here, we an overview conjugates, better equivalents antibody-drug as next generation drugs required precise targeting, enhanced cellular permeability, improved drug selectivity, reduced toxicity efficient cancers. We discuss basic components conjugates release action, including cytotoxins from linker. also present peptide-drug under different stages clinical development well regulatory other challenges.
Язык: Английский
Процитировано
61
Frontiers in Endocrinology, Год журнала: 2022, Номер 13
Опубликована: Окт. 13, 2022
Incretin-based therapies with glucagon-like peptide-1 receptor agonists (GLP-1RA) are already established in the treatment of type 2 diabetes (T2D). The development novel dual- or triple-receptor that bind to receptors not only for GLP-1 but also glucose-dependent insulinotropic polypeptide (GIP) and/or glucagon is intended address different metabolic pathways carbohydrate, lipid, and protein metabolism simultaneously. Dual- acting via postreceptor seem attractive view potentially additive synergistic effects T2D obesity. Recently, first approval a dual-receptor agonist marks an important step this development. GIP/GLP-1-receptor tirzepatide was approved by Food Drug Administration (FDA) USA once-weekly subcutaneous injections May 2022 has just received positive opinion from European Medicines Agency (EMA). Tirzepatide dose-dependently leads clinically significant reductions glycemic parameters body weight been shown have stronger reducing these than standard antidiabetic therapy. This article summarizes current clinical study program respective outcomes highlights further potential indications obesity other comorbidities T2D.
Язык: Английский
Процитировано
47
International Journal of Obesity, Год журнала: 2023, Номер 47(10), С. 883 - 892
Опубликована: Июль 17, 2023
Язык: Английский
Процитировано
32
Journal of Controlled Release, Год журнала: 2023, Номер 363, С. 415 - 434
Опубликована: Окт. 1, 2023
Язык: Английский
Процитировано
30
Nutrients, Год журнала: 2023, Номер 15(5), С. 1096 - 1096
Опубликована: Фев. 22, 2023
Diabetes mellitus is a complex disorder characterized by insufficient insulin production or resistance, which results in lifelong dependence on glucose-lowering drugs for almost all patients. During the fight with diabetes, researchers are always thinking about what characteristics ideal hypoglycemic should have. From point of view drugs, they maintain effective control blood sugar, have very low risk hypoglycemia, not increase decrease body weight, improve β-cell function, and delay disease progression. Recently, advent oral peptide such as semaglutide, brings exciting hope to patients chronic diabetes. Legumes, an excellent source protein, peptides, phytochemicals, played significant roles human health throughout history. Some legume-derived peptides encouraging anti-diabetic potential been gradually reported over last two decades. Their mechanisms also clarified at some classic diabetes treatment targets, receptor signaling pathway other related pathways involved progress key enzymes including α-amylase, α-glucosidase, dipeptidyl peptidase-IV (DPP-4). This review summarizes activities from legumes discusses prospects these peptide-based type 2 (T2D) management.
Язык: Английский
Процитировано
28
Diabetes Obesity and Metabolism, Год журнала: 2023, Номер 25(12), С. 3766 - 3778
Опубликована: Сен. 12, 2023
Abstract Aim To perform a meta‐analysis to quantify the effect of tirzepatide on blood pressure and lipids. Methods PubMed, Ovid/Medline, Web Science, Scopus, Cochrane Library CINAHL databases were screened randomized controlled trials evaluating effects either or lipid profiles included. Results Seven have investigated profiles. Regardless dose administered, resulted in significant decreases systolic median −4.20 (95% confidence interval [CI] −5.17 −3.23) mmHg for 5 mg, −5.34 (−6.31 −4.37) 10 −5.77 (−6.73 −4.81) 15 mg. At all three once‐weekly doses, treatment total cholesterol levels: −3.76% CI −5.20% −2.31%) mg; −4.63% (−6.07% −3.19%) −5.93% (−7.36% −4.49%) Additionally, led increased high‐density lipoprotein (HDL) levels decreased low‐density (LDL) triglyceride levels. Conclusions Tirzepatide induced clinically meaningful reductions diastolic pressure, cholesterol, LDL triglycerides, along with increases level HDL cholesterol.
Язык: Английский
Процитировано
27
Frontiers in Endocrinology, Год журнала: 2023, Номер 14
Опубликована: Окт. 16, 2023
Purpose A systematic review and meta-analysis was conducted to synthesize the available data from clinical trials assess safety issues of tirzepatide (pancreatitis gallbladder or biliary disease) in type 2 diabetes (T2D) obesity. Methods search three electronic databases, namely Embase, PubMed, Cochrane Library, up until March 1, 2023, identify randomized controlled (RCTs) comparing either placebo active hypoglycemic drugs individuals with T2D Heterogeneity assessed using I2 value Cochran’s Q test, a fixed effects model employed estimate profile tirzepatide. The outcomes interest, including pancreatitis, composite diseases, cholecystitis, cholelithiasis were evaluated. (The diseases incorporated cholelithiasis, other disorders, diseases.) Results total nine 9871 participants (6828 group 3043 control group) that met pre-specified criteria included. When compared all groups consisting basal insulin (glargine degludec), selective GLP1-RA (dulaglutide semaglutide once weekly), placebo, an increased risk pancreatitis not found be significantly associated (RR 1.46, [95% CI] 0.59 3.61; = 0.0%, p 0.436). For disease, disease 1.97, 1.14 3.42; 0.558), but cholecystitis diseases. Conclusion Based on currently data, appears safe regarding pancreatitis. However, outcome observed RCTs warrants further attention physicians practice. Systematic registration https://www.crd.york.ac.uk/PROSPERO , identifier CRD42023412400.
Язык: Английский
Процитировано
26