Trends in Antidiabetic Drug Discovery: FDA Approved Drugs, New Drugs in Clinical Trials and Global Sales

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 12

Published: Jan. 19, 2022

Type 2 diabetes mellitus (T2DM) continues to be a substantial medical problem due its increasing global prevalence and because chronic hyperglycemic states are closely linked with obesity, liver disease several cardiovascular diseases. Since the early discovery of insulin, numerous antihyperglycemic drug therapies treat have been approved, also discontinued, by United States Food Drug Administration (FDA). To provide an up-to-date account current trends antidiabetic pharmaceuticals, this review offers comprehensive analysis main classes compounds their mechanisms: insulin types, biguanides, sulfonylureas, meglitinides (glinides), alpha-glucosidase inhibitors (AGIs), thiazolidinediones (TZD), incretin-dependent therapies, sodium-glucose cotransporter type (SGLT2) combinations thereof. The number therapeutic alternatives T2DM now there nearly 60 drugs approved FDA. Beyond 100 additional agents being evaluated in clinical trials. In addition standard treatments therapy metformin, new combinations, e.g., containing SGLT2 dipeptidyl peptidase-4 (DPP4) inhibitors, that gained use during last decade. Furthermore, interesting alternatives, such as lobeglitazone, efpeglenatide tirzepatide, ongoing Modern drugs, glucagon-like peptide-1 (GLP-1) receptor agonists, DPP4 popularity on pharmaceutical market, while less expensive over counter developing economies. large heterogeneity is creating push towards more personalized accessible treatments. We describe trials, which may help achieve near future.

Language: Английский

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Modular cytokine receptor-targeting chimeras for targeted degradation of cell surface and extracellular proteins

Nature Biotechnology, Journal Year: 2022, Volume and Issue: 41(2), P. 273 - 281

Published: Sept. 22, 2022

Abstract Targeted degradation of cell surface and extracellular proteins via lysosomal delivery is an important means to modulate biology. However, these approaches have limitations due lack modularity, ease development, restricted tissue targeting applicability both proteins. We describe a strategy, termed cytokine receptor-targeting chimeras (KineTACs), that addresses limitations. KineTACs are fully genetically encoded bispecific antibodies consisting arm, which binds its cognate receptor, target-binding arm for the protein interest. show containing CXCL12 can use decoy recycling CXCR7, target variety lysosome degradation. Additional were designed harness other CXCR7-targeting cytokines, CXCL11 vMIPII, interleukin-2 (IL-2) IL-2. Thus, represent general, modular, selective simple strategy inducing targets with broad or tissue-specific distribution.

Language: Английский

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Nanoparticles in Clinical Trials: Analysis of Clinical Trials, FDA Approvals and Use for COVID-19 Vaccines

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(1), P. 787 - 787

Published: Jan. 2, 2023

Nanoparticles are heterologous small composites that usually between 1 and 100 nanometers in size. They applied many areas of medicine with one them being drug delivery. have a number advantages as carriers which include reduced toxic effects, increased bioavailability, their ability to be modified for specific tissues or cells. Due the exciting development nanotechnology concomitant advances biotechnology medicine, clinical trials devoted nanoparticles delivery is growing rapidly. Some nanoparticles, lipid-based types, particular, played crucial role developing manufacturing two COVID-19 vaccines-Pfizer Moderna-that now widely used. In this analysis, we provide quantitative survey using during period from 2002 2021 well recent FDA-approved drugs (since 2016). A total 486 were identified clinicaltrials.gov database. The prevailing types liposomes (44%) protein-based formulations (26%) period. most commonly investigated content paclitaxel (23%), metals (11%), doxorubicin (9%), bupivacaine various vaccines (both 8%). Among nanoparticle drugs, polymeric (29%), liposomal (22%) (21%) common. also discuss differential diverse groups content, underlying factors behind trends.

Language: Английский

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AlphaFold2 protein structure prediction: Implications for drug discovery

Current Opinion in Structural Biology, Journal Year: 2023, Volume and Issue: 78, P. 102526 - 102526

Published: Jan. 6, 2023

Language: Английский

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Pharmacological treatment of migraine: Drug classes, mechanisms of action, clinical trials and new treatments

British Journal of Pharmacology, Journal Year: 2021, Volume and Issue: 178(23), P. 4588 - 4607

Published: Aug. 11, 2021

Migraine is the sixth most prevalent disease globally, a major cause of disability, and it imposes an enormous personal socio‐economic burden. treatment often limited by insufficient therapy response, leading to need for individually adjusted treatment. In this review, we analyse historical current pharmaceutical development approaches in acute chronic migraine based on comprehensive systematic analysis Food Drug Administration (FDA)‐approved drugs those under investigation. The therapeutics has significantly intensified during last 3 years, as shown our trends drug between 1970 2020. spectrum targets expanded considerably, which been accompanied increase number specialised clinical trials. This review highlights mechanistic implications FDA‐approved currently investigated discusses future therapeutic options identified classes interest.

Language: Английский

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Approval success rates of drug candidates based on target, action, modality, application, and their combinations

Clinical and Translational Science, Journal Year: 2021, Volume and Issue: 14(3), P. 1113 - 1122

Published: April 8, 2021

The current success rate of a drug candidate, from the beginning clinical trial to receiving marketing approval, is about 10%-20%, and it has not changed during past few decades. Therefore, pharmaceutical companies are under pressure select one compound, among many others, with high probability success. differences in features affect their probabilities approval In this study, we examined rates candidates, developed United States, European Union, or Japan, by focusing on four parameters ("drug target," "drug action," modality," application") combinations, identified factors that conditioned outcome development process. We obtained total 12.8%, after evaluating 3999 compounds. Moreover, analyzing combinations these parameters, drugs corresponded following categories-a stimulant action an enzyme target biologics (excluding monoclonal antibody) modality-were (34.1% 31.3%, respectively). Univariate multivariate logistic regression analyses revealed action, "B" (blood blood forming organs), "G" (genito-urinary system sex), "J" (anti-infectives for systemic use) application were statistically associated rates. found several affected Our results could assist candidates and, thus, efficiently conducting

Language: Английский

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Treatment of ADHD: Drugs, psychological therapies, devices, complementary and alternative methods as well as the trends in clinical trials

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: Nov. 17, 2022

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders having a high influence on social interactions. The number approved treatments and clinical trials for ADHD have increased markedly during recent decade. This analytical review provides quantitative overview existing pharmacological non-pharmacological methods investigated in 1999-2021. A total 695 interventional were manually assessed from clinicaltrial.gov with search term « ADHD», trial data has been used analysis. clear majority studies therapies (∼80%), including many behavioral options, such as skills training, sleep physical activity interventions, meditation hypnotherapy. Devices, complementary other alternative treatment are also gaining attention. group accounts ∼20% all studies. drug classes include central nervous system stimulants (e.g., methylphenidate hydrochloride, lisdexamfetamine dimesylate, amphetamine sulfate, mixed salts, combination dexmethylphenidate hydrochloride serdexmethylphenidate chloride), selective noradrenaline reuptake inhibitors (atomoxetine, viloxazine), alpha2 adrenergic receptor agonists (guanfacine clonidine hydrochloride). Several antidepressants bupropion vortioxetine), atypical antipsychotics quetiapine, aripiprazole) but these yet not by FDA treatment. We discuss trends provide an new agents therapies, targets, novel options.

Language: Английский

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Role of the Synergistic Interactions of Environmental Pollutants in the Development of Cancer

GeoHealth, Journal Year: 2022, Volume and Issue: 6(4)

Published: April 1, 2022

Abstract There is a growing awareness that the large number of environmental pollutants we are exposed to on daily basis causing major health problems. Compared traditional studies focus individual pollutants, there relatively few how mixtures interact. Several have reported relationship between and development cancer, even when pollutant levels below toxicity reference values. The possibility synergistic interactions different could explain low concentrations can cause These intricate molecular occur through wide variety mechanisms, our understanding physiological effects still limited. purpose this paper discuss recent reports address possible types promote cancer development. Our literature suggest key biological pathways frequently implicated in such processes. include increased production reactive oxygen species, activation by cytochrome P450, aryl hydrocarbon receptor signaling, among others. We need understand pathological vulnerability not only relation basic genetics gene expression, but also terms measurable exposure contaminants. mention for significant improvements future using multitude disciplines, as high‐throughput study models, better tools quantifying patients, innovative pharmacological toxicological studies, high‐efficiency computer analysis, which allow us analyze mechanisms mixtures.

Language: Английский

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Stimuli‐Responsive PROTACs for Controlled Protein Degradation

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(39)

Published: July 20, 2023

Proteolysis Targeting Chimeras (PROTACs) represent a promising therapeutic modality to address undruggable and resistant issues in drug discovery. However, potential on-target toxicity remains clinically challenging. We developed generalized caging strategy synthesize series of stimuli-responsive PROTACs (sr-PROTACs) with diverse molecular blocks bearing robust cleavable linkers, presenting "turn on" features manipulating protein degradation. By leveraging pathological cues, such as elevated ROS, phosphatase, H2 S, or hypoxia, external triggers, ultraviolet light, X-Ray, bioorthogonal reagents, we achieved site-specific activation traceless release original through de-caging subsequent self-immolative cleavage, realizing selective uptake controlled degradation vitro. An vivo study revealed that two sr-PROTACs phosphate- fluorine-containing cages exhibited high solubility long plasma exposure, which were specifically activated by tumor overexpressing phosphatase low dosage X-Ray irradiation situ, leading efficient potent remission. With more reactive biomarkers be screened from clinical practice, our library could provide general tool design activatable PROTACs, prodrugs, antibody-drug conjugates, smart biomaterials for personalized treatment, tissue engineering regenerative medicine.

Language: Английский

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Identifying therapeutic targets for cancer among 2074 circulating proteins and risk of nine cancers

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: April 29, 2024

Circulating proteins can reveal key pathways to cancer and identify therapeutic targets for prevention. We investigate 2,074 circulating risk of nine common cancers (bladder, breast, endometrium, head neck, lung, ovary, pancreas, kidney, malignant non-melanoma) using cis protein Mendelian randomisation colocalization. conduct additional analyses adverse side-effects altering map drug targets. Here we find 40 associated with cancers, such as PLAUR breast [odds ratio per standard deviation increment: 2.27, 1.88-2.74], high-mortality CTRB1 pancreatic [0.79, 0.73-0.85]. also potential effects protein-altering interventions reduce risk, hypertension. Additionally, report 18 that existing drugs 15 are not currently under clinical investigation. In sum, protein-cancer links improve our understanding aetiology. demonstrate the wider consequence any intervention on well-being morbidity is required interpret utility future

Language: Английский

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