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1.
JAMA ; 329(1): 87-89, 2023 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-36594955

RESUMO

This study quantifies the revenue earned on all brand-name inhalers approved by the US Food and Drug Administration from 2000 to 2021 and compared earnings before and after expiration of primary patents on these products.


Assuntos
Indústria Farmacêutica , Competição Econômica , Nebulizadores e Vaporizadores , Patentes como Assunto , Medicamentos Genéricos , Competição Econômica/economia , Nebulizadores e Vaporizadores/economia , Estados Unidos , Patentes como Assunto/legislação & jurisprudência , Indústria Farmacêutica/economia , Indústria Farmacêutica/legislação & jurisprudência
2.
Nature ; 613(7942): 138-144, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36600070

RESUMO

Theories of scientific and technological change view discovery and invention as endogenous processes1,2, wherein previous accumulated knowledge enables future progress by allowing researchers to, in Newton's words, 'stand on the shoulders of giants'3-7. Recent decades have witnessed exponential growth in the volume of new scientific and technological knowledge, thereby creating conditions that should be ripe for major advances8,9. Yet contrary to this view, studies suggest that progress is slowing in several major fields10,11. Here, we analyse these claims at scale across six decades, using data on 45 million papers and 3.9 million patents from six large-scale datasets, together with a new quantitative metric-the CD index12-that characterizes how papers and patents change networks of citations in science and technology. We find that papers and patents are increasingly less likely to break with the past in ways that push science and technology in new directions. This pattern holds universally across fields and is robust across multiple different citation- and text-based metrics1,13-17. Subsequently, we link this decline in disruptiveness to a narrowing in the use of previous knowledge, allowing us to reconcile the patterns we observe with the 'shoulders of giants' view. We find that the observed declines are unlikely to be driven by changes in the quality of published science, citation practices or field-specific factors. Overall, our results suggest that slowing rates of disruption may reflect a fundamental shift in the nature of science and technology.


Assuntos
Invenções , Patentes como Assunto , Relatório de Pesquisa , Tecnologia , Humanos , Invenções/estatística & dados numéricos , Invenções/tendências , Pesquisadores , Tecnologia/estatística & dados numéricos , Tecnologia/tendências , Patentes como Assunto/estatística & dados numéricos , Relatório de Pesquisa/tendências , Conjuntos de Dados como Assunto , Editoração/estatística & dados numéricos , Editoração/tendências , Fatores de Tempo , Difusão de Inovações
3.
J Prev Alzheimers Dis ; 10(1): 50-68, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36641610

RESUMO

Alzheimer's disease (AD) is the most common form of dementia. There is currently no cure, and the available pharmacological treatment focuses on treating the symptoms. This study aimed to analyze the pharmacological treatments for AD protected in the US Patent Office. The Matheo Patent software was used to search for patents granted in the 2010-2020 period in the USPTO database. The search strategy «Alzheimer¼ was used in title and abstract and the International Patent Classification (IPC) codes A61P* and A61K*. The selected patents were divided into six categories according to therapeutic target. Complementary information from scientific databases was used to determine the stage of investigation and efficacy of the patented molecules. In the analyzed period, 58 patents were granted: 10 directed to Aß peptide metabolism and deposition, three to tau, seven to inflammation, nine to cholinergic, two to glutamatergic and 27 to other targets. More than 80.0% belong to holders from the USA, France, and Japan. The molecules Elenbecestat and LY3202626 decreased the burden of Aß plaques without significant cognitive improvement, Donanemab is in Phase 3 clinical trial, and the FDA has designated it Breakthrough Therapy. CPC-201 and PXT864 demonstrated, in Phase 2, good tolerability and improvement of AD symptoms. Most of the inventions are focused on treating the earliest phase of AD. The most advanced treatments in their research are those focused on treating Aß accumulation. More studies are needed to prove the efficacy of the patented molecules.


Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/tratamento farmacológico , França , Japão , Estados Unidos , Patentes como Assunto
4.
Expert Opin Ther Pat ; 32(10): 1067-1077, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36198171

RESUMO

INTRODUCTION: Rearranged during transfection (RET) is a transmembrane receptor tyrosine kinase. Aberrations in RET signaling due to mutations, gene fusions, or overexpression can lead to carcinomas. Six inhibitors have been approved for the treatment of RET-driven cancers: vandetanib, cabozantinib, lenvatinib, sorafenib, selpercatinib, and pralsetinib. Only selpercatinib and pralsetinib have been developed specifically for RET, while the remaining are multikinase inhibitors. Several other RET targeted candidates are under clinical development. AREAS COVERED: This review covers recent patent literature describing small molecules that are active against RET since 2016 till present. EXPERT OPINION: RET represents a major therapeutic target as its alterations occur in nearly 2% of all cancers. Recent approvals for RET targeted therapy have been developed specifically to target the RET oncogene. These approvals represent a paradigm shift from the last decade to now focus on the development of selective RET inhibitors rather than multikinase inhibitors. These newly approved RET inhibitors still have clinical issues with drug resistance. It is imperative that the next iteration of RET inhibitors are developed to block common treatment-resistant mutations. To accomplish this, RET inhibitors should be developed in concert with genomic profiling to ensure the most relevant clinical mutations are targeted.


Assuntos
Neoplasias Pulmonares , Proteínas Proto-Oncogênicas c-ret , Humanos , Proteínas Proto-Oncogênicas c-ret/genética , Sorafenibe/uso terapêutico , Neoplasias Pulmonares/patologia , Patentes como Assunto , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Transfecção
5.
Expert Opin Ther Pat ; 32(10): 1079-1095, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36189616

RESUMO

INTRODUCTION: Dihydrofolate reductase (DHFR) plays an important role in the biosynthesis of amino acid and folic acid. It participates by reducing dihydrofolate to tetrahydrofolate, in the presence of nicotinamide dinucleotide phosphate cofactor, and has been verified by various clinical studies to use DHFR as a target for the treatment of cancer and various bacterial infections. AREA COVERED: In this review, we have disclosed patents of synthetics and natural DHFR inhibitors with diaminopyrimidine and quinazoline nucleus from 2001. Additionally, this review highlights the clinical progression of numerous DHFR inhibitors received from the last five years. EXPERT OPINION: From 2001 to 2021, numerous active chemical scaffolds have been introduced and are exposed as lead candidates that have entered clinical trials as potent DHFR inhibitors. Moreover, researchers have paid considerable attention to the development of a new class of DHFR inhibitors with higher selectivity and potency. This development includes synthesis of synthetic as well as natural compounds that are potent DHFR inhibitors. On the basis of literature review, we can anticipate that there are a huge number of novel active molecules available for the future that could possess superior abilities to target this enzyme with a profound pharmacological profile.


Assuntos
Antagonistas do Ácido Fólico , Humanos , Antagonistas do Ácido Fólico/farmacologia , Antagonistas do Ácido Fólico/química , Tetra-Hidrofolato Desidrogenase/química , Tetra-Hidrofolato Desidrogenase/metabolismo , Patentes como Assunto , Ácido Fólico , Aminoácidos , Tetra-Hidrofolatos , Quinazolinas , Niacinamida , Fosfatos
6.
Expert Opin Ther Pat ; 32(10): 1097-1122, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36175357

RESUMO

INTRODUCTION: Fibrosis is a disease that damages organs and even causes death. Because of the complicated pathogenesis, the development of drugs for fibrosis is challenging. In the lysophosphatidic acid receptor type 1 (LPA1) signaling pathway, LPA1 and its downstream Rho-associated coiled-coil forming protein kinase (ROCK) are related to the process of fibrosis. Targeting LPA1 signaling pathway is a potential strategy for the treatment of fibrosis. AREA COVERED: This review describes the process of fibrosis mediated by the LPA1 signaling pathway and then summarizes LPA1 antagonist patents reported since 2010 and ROCK inhibitor patents since 2017 according to their scaffolds based on the Cortellis Drug Discovery Intelligence database. Information on LPA1 antagonists entering clinical trials is integrated. EXPERT OPINION: Over the past decade, a large number of antagonists targeting the LPA1 signaling pathway have been patented for fibrosis therapy. A limited number of compounds have entered clinical trials. Different companies and research groups have used different scaffolds when designing compounds for fibrosis therapy. Therefore, LPA1 and ROCK are competitive targets for the development of new therapies for fibrosis to provide a potential treatment method for fibrosis in the future.


Assuntos
Receptores de Ácidos Lisofosfatídicos , Quinases Associadas a rho , Humanos , Receptores de Ácidos Lisofosfatídicos/metabolismo , Patentes como Assunto , Fibrose , Transdução de Sinais , Lisofosfolipídeos/metabolismo
7.
Expert Opin Ther Pat ; 32(10): 1055-1065, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36120913

RESUMO

INTRODUCTION: Cyclin-dependent kinase 12 (CDK12) belongs to the CDK family of serine/threonine protein kinases and is associated with cyclin K to exert its biological functions, including regulating gene transcription, mRNA processing, and translation. Increasing evidences demonstrate the importance of CDK12 in various human cancers, illustrating its potential as both biomarker and therapeutic target. In addition, CDK12 is also a promising target for the treatment of myotonic dystrophy type 1. Efforts have been taken to discover small molecule inhibitors to validate this important therapeutic target. AREAS COVERED: This review covers the patented CDK12 inhibitors from 2016 to present, as well as these from peer-reviewed literature. It provides the reader an update of the discovery strategies, chemical structures, and molecular profiling of all available CDK12 inhibitors. EXPERT OPINION: CDK12 inhibitors with various mechanism of actions have been discovered, and it is a great set of tools to evaluate the therapeutic potential of CDK12 in different disease models. CDK12 inhibitors have shown promising results in myotonic dystrophy type 1 mouse model and several preclinical cancer models either as single agent or combination with other anti-cancer agents. Its therapeutic value awaits more rigorous preclinical testing and further clinical investigation.


Assuntos
Distrofia Miotônica , Neoplasias , Animais , Humanos , Camundongos , Quinases Ciclina-Dependentes/genética , Quinases Ciclina-Dependentes/metabolismo , Ciclinas/genética , Ciclinas/metabolismo , Ciclinas/uso terapêutico , Distrofia Miotônica/tratamento farmacológico , Neoplasias/tratamento farmacológico , Neoplasias/genética , Patentes como Assunto , RNA Mensageiro/uso terapêutico , Serina , Treonina/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia
9.
J Health Econ ; 85: 102671, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36030748

RESUMO

This paper studies the impact of the first joint licensing platform for patented drugs, the Medicines Patent Pool, on global drug diffusion and innovation. The pool allows generic firms worldwide to license drug bundles cheaply and conveniently for sales in a set of developing countries. I construct a novel dataset from licensing contracts, public procurement, clinical trials, and drug approvals. Using difference-in-differences methods, I find that the pool leads to substantial increases in the generic supply of drugs purchased, particularly in countries with stronger patent protection. In addition, there are some positive increases in clinical trials and drug product approvals after a compound enters the pool, mostly by firms outside the pool.


Assuntos
Aprovação de Drogas , Medicamentos Genéricos , Difusão de Inovações , Indústria Farmacêutica , Humanos , Patentes como Assunto
10.
Expert Opin Ther Pat ; 32(9): 939-952, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35929879

RESUMO

INTRODUCTION: Iron oxide nanoparticles (IONPs) hold the edges of great magnetic properties and fine nanoparticle characteristics, making them an attractive therapeutic agent. In the past seven years, more in-depth investigations were devoted to the intrinsic structure, magnetic properties, and biological effects of IONPs, expanding the range of their therapeutic application scenes. AREAS COVERED: This review focuses on the development of IONPs for biomedical applications from the angle of the patent literature reported during the period 2015-2021. EXPERT OPINION: While the magnetic properties of IONPs have been extensively explored, the precise control of IONP behavior through external magnetic fields remains a challenge. Further digging into the biological effects of IONPs will facilitate the development of IONP-based immune therapies. Long-term reliable safety evaluations are of necessity and significance to promote the process of clinical translation.


Assuntos
Nanopartículas de Magnetita , Nanopartículas , Compostos Férricos , Humanos , Nanopartículas Magnéticas de Óxido de Ferro , Nanopartículas de Magnetita/química , Nanopartículas/química , Patentes como Assunto
11.
Expert Opin Ther Pat ; 32(9): 969-1001, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35993146

RESUMO

INTRODUCTION: Oxadiazole is a unique class of heterocycle, possessing numerous important biomedical and therapeutic applications, such as anti-bacterial, anti-cancer, anti-inflammatory, inhibitors for diverse enzymes, receptor modulators, and neuroprotective properties. The rapid development in the field of oxadiazole-containing structures is confirmed by the development of numerous clinical drugs, such as doxazosin, nesapidil, pleconaril, fasiplon, ataluren, zibotentan, and prenoxdiazine as selected examples. AREAS COVERED: This review provides a comprehensive overview of the range of biological applications of oxadiazole-containing drugs in a range of patents from 2013 to 2021. The information was collected from available data sources including SciFinder, Reaxys, MedLine, and Chemical Abstracts. EXPERT OPINION: Oxadiazole is an established class of compounds with fascinating biological properties. The importance of oxadiazoles can be recognized by their enormous application in a wide spectrum of medicinal chemistry from anticancer, lantibiotics, and antidiabetics to their use in agriculture and neuroprotection. For instance, the oxadiazole-based compounds have shown the ability to modulate a variety of receptors including the M4 receptor agonists, S1P1 receptor modulators, SSTR5 antagonists, orexin type-2 receptor agonists, liver X receptor agonists, and many more. This testifies to the special features associated with the oxadiazole scaffold, making it a significant pharmacophore.


Assuntos
Oxidiazóis , Patentes como Assunto , Anti-Inflamatórios/farmacologia , Doença Crônica , Humanos , Oxidiazóis/química , Oxidiazóis/farmacologia , Preparações Farmacêuticas
12.
Expert Opin Ther Pat ; 32(9): 1003-1026, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35993382

RESUMO

INTRODUCTION: The anti-apoptotic BCL-2 family proteins, such as BCL-2, BCL-XL, and MCL-1, are excellent cancer therapeutic targets. The FDA approval of BCL-2 selective inhibitor venetoclax in 2016 validated the strategy of targeting these proteins with BH3 mimetic small molecule inhibitors. AREAS COVERED: This review provides an overview of the patent literature between 2016 and 2021 covering inhibitors and PROTACs of the anti-apoptotic BCL-2 proteins. EXPERT OPINION: Since the FDA approval of venetoclax, tremendous efforts have been made to develop its analogues with improved drug properties. These activities will likely result in new drugs in coming years. Significant progress on MCL-1 inhibitors has also been made, with multiple compounds entering clinical trials. However, MCL-1 inhibition could cause on-target toxicity to normal tissues especially the heart. Similar issue exists with BCL-XL inhibitors, which cause on-target platelet toxicity. To overcome this issue, several strategies have been applied, including prodrug, dendrimer-based drug delivery, antibody-drug conjugate (ADC), and proteolysis targeting chimera (PROTAC); and amazingly, each of these approaches has resulted in a drug candidate entering clinical trials. We envision technologies like ADC and PROTAC could also be utilized to increase the therapeutic index of MCL-1 inhibitors.


Assuntos
Antineoplásicos , Proteínas Reguladoras de Apoptose , Humanos , Antineoplásicos/farmacologia , Apoptose , Proteínas Reguladoras de Apoptose/metabolismo , Linhagem Celular Tumoral , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Patentes como Assunto , Proteínas Proto-Oncogênicas c-bcl-2
13.
Expert Opin Ther Pat ; 32(9): 953-968, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35982031

RESUMO

INTRODUCTION: Bromodomain and extraterminal (BET) proteins are epigenetic readers that regulate gene transcription and cell growth by binding to acetylated lysine residues on histones. They are involved in many physiological processes and pathological conditions, such as cancer, inflammation, and metabolic diseases. Blockade of BET proteins has become an encouraging approach for the treatment of these human diseases, especially cancer. To date, a number of potent and specific BET inhibitors have been discovered and many of them have entered clinical trials. AREAS COVERED: This review aims at providing an overview of molecular mechanisms of BET inhibitors and highlighting the research advancements published in recent patent literatures between 2018 and 2021. Web of Science, PubMed, SciFinder, WIPO, EPO, USPTO and CNIPA databases were used for searching the literature and patents for BET inhibitors. EXPERT OPINION: In recent years, an increasing number of structurally diverse BET inhibitors have been identified, including pan BET inhibitors, BD1 or BD2 selective BET inhibitors, bivalent BET inhibitors, kinase and BET dual inhibitors, and BET-PROTACs. Despite many challenges, BET inhibitors have high potential in the treatment of cancer and other diseases, and the development of next-generation BET inhibitors could be promising.


Assuntos
Neoplasias , Fatores de Transcrição , Proliferação de Células , Regulação da Expressão Gênica , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Patentes como Assunto , Fatores de Transcrição/metabolismo
14.
Expert Opin Ther Pat ; 32(9): 933-937, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35965439

RESUMO

Helicase-primase is an interesting target for small-molecule therapy of herpes simplex virus (HSV) infections. With amenamevir already approved for varicella-zoster virus and with pritelivir's granted breakthrough therapy designation for the treatment of acyclovir-resistant HSV infections in immunocompromised patients, the target has sparked interest for me-too approaches. We describe the opportunities and limitations of the helicase-primase inhibitor patent portfolio from Phaeno Therapeutics and propose the structure of their drug candidate HN0037, which has been in-licensed from Medshine Discovery.


Assuntos
DNA Primase , Herpes Simples , Antivirais/uso terapêutico , DNA Helicases , Herpes Simples/tratamento farmacológico , Humanos , Patentes como Assunto , Proteínas Virais/uso terapêutico
15.
Expert Opin Ther Pat ; 32(9): 1027-1042, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35914778

RESUMO

INTRODUCTION: Lysine-specific demethylase 1 (LSD1), which belongs to the demethylase of non-histone proteins, is believed to promote cancer cell proliferation and metastasis by modifying histones. LSD1 dysfunction may play a key role in a variety of cancers, such as acute myeloid leukemia and non-small cell lung cancer, indicating that LSD1 is a promising epigenetic target for cancer therapy. Many different types of small molecule LSD1 inhibitors have been developed and shown to inhibit tumor cell proliferation, invasion, and migration, providing a new treatment strategy for solid tumors. AREAS COVERED: This review summarizes the progress of LSD1 inhibitor research in the last four years, including selected new patents and article publications, as well as the therapeutic potential of these compounds. EXPERT OPINION: Natural products offer a promising prospect for developing novel potent LSD1 inhibitors, as structural design and activity of irreversible and reversible inhibitors have been continuously optimized since the discovery of the LSD1 target in 2004. The use of 'microtubule-binding agents' and 'dual-agent combination' has recently become a new anticancer technique, reducing the resistance and adverse reactions of traditional drugs. Several microtubule-binding drugs have been used successfully in clinical practice, providing structural scaffolds and new ideas for the development of safer drugs.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Inibidores Enzimáticos/farmacologia , Histona Desmetilases , Histonas/química , Histonas/metabolismo , Humanos , Patentes como Assunto
16.
Expert Opin Ther Pat ; 32(10): 1043-1053, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36043503

RESUMO

INTRODUCTION: In methylthioadenosine phosphorylase (MTAP)-deficient tumor cells, reduced S-adenosylmethionine (SAM) levels in the context of elevated methylthioadenosine (MTA) has been hypothesized to lead to inhibition of protein arginine methyltransferase 5 (PRMT5) and tumor growth inhibition. Inhibitors of methionine adenosyltransferase 2A (MAT2a) prevent the synthesis of SAM from methionine and have therefore attracted increasing attention as potential chemotherapeutic agents in cancers characterized by MTAP-loss. AREAS COVERED: This review covers patent applications between January 2018 and December 2021. 18 patent applications from 5 different applicants are evaluated. EXPERT OPINION: Recent advances in the field show a significant interest in the MAT2a therapeutic hypothesis. Agios and Ideaya in particular have capitalized on an allosteric binding mode first published by Pfizer in at least two of the filings during this time period, leading to potent, selective inhibitors. They have advanced MAT2a inhibitors to phase I clinical studies to explore their benefit to patients suffering with MTAP-deficient solid tumors or lymphoma. Whilst the other patent disclosures during this time frame have not led to disclosed candidates, the trials initiated by Agios and Ideaya studies will clearly inform on the potential for such inhibitors as viable therapeutic agents either as single agent or in combination.


Assuntos
Metionina Adenosiltransferase , Neoplasias , Humanos , Metionina Adenosiltransferase/metabolismo , S-Adenosilmetionina/metabolismo , S-Adenosilmetionina/uso terapêutico , Proteína-Arginina N-Metiltransferases/metabolismo , Pemetrexede/uso terapêutico , Patentes como Assunto , Neoplasias/tratamento farmacológico , Metionina/metabolismo , Metionina/uso terapêutico
17.
Bioengineered ; 13(6): 14503-14518, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35758066

RESUMO

Biosimilars play an important role in reducing the burden on patients and increasing the market competition. Biosimilar monoclonal antibodies are currently one of the hotspots of research and development in China with policies support. With the continuous improvement of policies, the enthusiasm for the research and development of biosimilars has increased year by year. The policy requirements in different periods have different degrees of impact on the patent applications of pharmaceutical companies. This review introduces the biosimilar monoclonal antibodies market status and approval process in China, analyzes the patents in this field, and helps pharmaceutical companies protect their intellectual property rights.


Assuntos
Anticorpos Monoclonais , Medicamentos Biossimilares , China , Humanos , Patentes como Assunto
18.
Expert Opin Ther Pat ; 32(8): 899-912, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35768160

RESUMO

INTRODUCTION: The Hippo pathway represents a new opportunity for the treatment of cancer. Overexpression of Yes-associated protein (YAP) or transcriptional coactivator with PDZ-binding motif (TAZ) or TEAD has been demonstrated in cancers and YAP mediates resistance to cancer drugs. Since 2018, the potential of this pathway has been illustrated by numerous articles and patents and the first drugs entering in clinical trial phase 1. AREAS COVERED: This review is limited to published patent applications that have disclosed direct small-molecule inhibitors of the YAP/TAZ-TEAD interaction. EXPERT OPINION: The YAP/TAZ-TEAD transcriptional complex is a promising target for the treatment of cancer. Approximately 30 international patents (used database: Sci-finder, query: TEAD; documents: patents; period: from 2017-January 2022) that disclose TEAD transcriptional inhibitors have been filled since 2018. The mechanism of action is not always described in the patents, we can divide the drugs into three different categories: (i) external TEAD ligands; (ii) non-covalent TEAD ligands of the palmitate pocket; (iii) covalent TEAD ligands, which bind into the palmitate pocket. The first molecules in clinical trial phase 1 are non-covalent TEAD ligands. The selective TEAD ligand have also been patented, published and selectivity could be of great interest for personalized medicine.


Assuntos
Neoplasias , Patentes como Assunto , Fatores de Transcrição de Domínio TEA , Proteínas de Sinalização YAP , Humanos , Ligantes , Neoplasias/tratamento farmacológico , Palmitatos , Fatores de Transcrição de Domínio TEA/antagonistas & inibidores , Proteínas de Sinalização YAP/antagonistas & inibidores
19.
Recent Pat Biotechnol ; 16(4): 329-354, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35549857

RESUMO

Stenotrophomonas maltophilia is an opportunistic pathogen that results in nosocomial infections in immunocompromised individuals. These bacteria colonize on the surface of medical devices and therapeutic equipment like urinary catheters, endoscopes, and ventilators, causing respiratory and urinary tract infections. The low outer membrane permeability of multidrug-resistance efflux systems and the two chromosomally encoded ß- lactamases present in S. maltophilia are challenging for arsenal control. The cell-associated and extracellular virulence factors in S. maltophilia are involved in colonization and biofilm formation on the host surfaces. The spread of antibiotic-resistant genes in the pathogenic S. maltophilia attributes to bacterial resistance against a wide range of antibiotics, including penicillin, quinolones, and carbapenems. So far, tetracycline derivatives, fluoroquinolones, and trimethoprim-sulfamethoxazole (TMP-SMX) are considered promising antibiotics against S. maltophilia. Due to the adaptive nature of the intrinsically resistant mechanism towards the number of antibiotics and its ability to acquire new resistance via mutation and horizontal gene transfer, it is quite tricky for medicinal contribution against S. maltophilia. The current review summarizes the literary data on pathogenicity, quorum sensing, biofilm formation, virulence factors, and antibiotic resistance of S. maltophilia.


Assuntos
Infecções por Bactérias Gram-Negativas , Stenotrophomonas maltophilia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Testes de Sensibilidade Microbiana , Infecções Oportunistas/microbiologia , Patentes como Assunto , Stenotrophomonas maltophilia/efeitos dos fármacos , Stenotrophomonas maltophilia/genética , Fatores de Virulência/genética , Fatores de Virulência/uso terapêutico , beta-Lactamases/genética , beta-Lactamases/uso terapêutico
20.
Expert Opin Ther Pat ; 32(8): 849-883, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35638744

RESUMO

INTRODUCTION: Monoamine oxidase (MAO) inhibitors are currently used as antidepressants (selective MAO-A inhibitors) or as co-adjuvants for neurodegenerative diseases (selective MAO-B inhibitors). The research within this field is attracting attention due to their crucial role in the modulation of brain functions, mood, and cognitive activity, and monoamine catabolism. AREAS COVERED: MAO inhibitors (2018-2021) are discussed according to their chemotypes. Structure-activity relationships are derived for each chemical scaffold (propargylamines, chalcones, indoles, benzimidazoles, (iso)coumarins, (iso)benzofurans, xanthones, and tetralones), while the chemical entities were divided into newly synthesized molecules and natural metabolites. The mechanism of action and type of inhibition are also considered. Lastly, new therapeutic applications are reported, which demonstrates the clinical potential of these inhibitors as well as the possibility of repurposing existing drugs for a variety of diseases. EXPERT OPINION: MAO inhibitors here reported exhibit different potencies and isoform selectivity. These compounds are clinically licensed for multi-faceted neurodegenerative pathologies due to their ability to also act against other relevant targets (cholinesterases, inflammation, and oxidative stress). Moreover, the drug repurposing approach is an attractive strategy by which MAO inhibitors may be applied for the treatment of prostate cancer, inflammation, vertigo, and type 1 diabetes.


Assuntos
Inibidores da Monoaminoxidase , Patentes como Assunto , Antidepressivos/farmacologia , Humanos , Inflamação/tratamento farmacológico , Monoaminoxidase/metabolismo , Inibidores da Monoaminoxidase/química , Inibidores da Monoaminoxidase/farmacologia , Relação Estrutura-Atividade
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