Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 42
Filtrar
1.
Proc Natl Acad Sci U S A ; 120(6): e2208866120, 2023 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-36716368

RESUMO

Canine distemper virus (CDV) is an enveloped RNA morbillivirus that triggers respiratory, enteric, and high incidence of severe neurological disorders. CDV induces devastating outbreaks in wild and endangered animals as well as in domestic dogs in countries associated with suboptimal vaccination programs. The receptor-binding tetrameric attachment (H)-protein is part of the morbilliviral cell entry machinery. Here, we present the cryo-electron microscopy (cryo-EM) structure and supramolecular organization of the tetrameric CDV H-protein ectodomain. The structure reveals that the morbilliviral H-protein is composed of three main domains: stalk, neck, and heads. The most unexpected feature was the inherent asymmetric architecture of the CDV H-tetramer being shaped by the neck, which folds into an almost 90° bent conformation with respect to the stalk. Consequently, two non-contacting receptor-binding H-head dimers, which are also tilted toward each other, are located on one side of an intertwined four helical bundle stalk domain. Positioning of the four protomer polypeptide chains within the neck domain is guided by a glycine residue (G158), which forms a hinge point exclusively in two protomer polypeptide chains. Molecular dynamics simulations validated the stability of the asymmetric structure under near physiological conditions and molecular docking showed that two receptor-binding sites are fully accessible. Thus, this spatial organization of the CDV H-tetramer would allow for concomitant protein interactions with the stalk and head domains without steric clashes. In summary, the structure of the CDV H-protein ectodomain provides new insights into the morbilliviral cell entry system and offers a blueprint for next-generation structure-based antiviral drug discovery.


Assuntos
Vírus da Cinomose Canina , Cinomose , Animais , Cães , Vírus da Cinomose Canina/genética , Simulação de Acoplamento Molecular , Microscopia Crioeletrônica , Subunidades Proteicas , Glicoproteínas
2.
Nanomedicine ; 47: 102607, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36167305

RESUMO

Extracellular vesicles (EVs), nanovesicles released by cells to effectively exchange biological information, are gaining interest as drug delivery system. Yet, analogously to liposomes, they show short blood circulation times and accumulation in the liver and the spleen. For tissue specific delivery, EV surfaces will thus have to be functionalized. We present a novel platform for flexible modification of EVs with target-specific ligands based on the avidin-biotin system. Genetic engineering of donor cells with a glycosylphosphatidylinositol-anchored avidin (GPI-Av) construct allows the isolation of EVs displaying avidin on their surface, functionalized with any biotinylated ligand. For proof of concept, GPI-Av EVs were modified with i) a biotinylated antibody or ii) de novo designed and synthesized biotinylated ligands binding carbonic anhydrase IX (CAIX), a membrane associated enzyme overexpressed in cancer. Functionalized EVs showed specific binding and uptake by CAIX-expressing cells, demonstrating the power of the system to prepare EVs for cell-specific drug delivery.


Assuntos
Vesículas Extracelulares , Diagnóstico por Imagem
3.
J Neuroinflammation ; 19(1): 304, 2022 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-36527076

RESUMO

BACKGROUND: Listeria monocytogenes (Lm) is a bacterial pathogen of major concern for humans and ruminants due to its neuroinvasive potential and its ability to cause deadly encephalitis (neurolisteriosis). On one hand, polymorphonuclear neutrophils (PMN) are key players in the defense against Lm, but on the other hand intracerebral infiltration with PMN is associated with significant neural tissue damage. Lm-PMN interactions in neurolisteriosis are poorly investigated, and factors inducing PMN chemotaxis to infectious foci containing Lm in the central nervous system (CNS) remain unidentified. METHODS: In this study, we assessed bovine PMN chemotaxis towards Lm and supernatants of infected endogenous brain cell populations in ex vivo chemotaxis assays, to identify chemotactic stimuli for PMN chemotaxis towards Lm in the brain. In addition, microglial secretion of IL-8 was assessed both ex vivo and in situ. RESULTS: Our data show that neither Lm cell wall components nor intact bacteria elicit chemotaxis of bovine PMN ex vivo. Moreover, astrocytes and neural cells fail to induce bovine PMN chemotaxis upon infection. In contrast, supernatant from Lm infected microglia readily induced chemotaxis of bovine PMN. Microglial expression and secretion of IL-8 was identified during early Lm infection in vitro and in situ, although IL-8 blocking with a specific antibody could not abrogate PMN chemotaxis towards Lm infected microglial supernatant. CONCLUSIONS: These data provide evidence that host-derived rather than bacterial factors trigger PMN chemotaxis to bacterial foci in the CNS, that microglia have a primary role as initiators of bovine PMN chemotaxis into the brain during neurolisteriosis and that blockade of these factors could be a therapeutic target to limit intrathecal PMN chemotaxis and PMN associated damage in neurolisteriosis.


Assuntos
Listeria monocytogenes , Humanos , Animais , Bovinos , Microglia , Neutrófilos/metabolismo , Quimiotaxia , Interleucina-8/metabolismo , Quimiotaxia de Leucócito
4.
Int J Mol Sci ; 23(20)2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36292935

RESUMO

SUMOylation is a reversible post-translational modification (PTM) involving covalent attachment of small ubiquitin-related modifier (SUMO) proteins to substrate proteins. Dysregulation of SUMOylation and deSUMOylation results in cellular malfunction and is linked to various diseases, such as cancer. Sentrin-specific proteases (SENPs) were identified for the maturation of SUMOs and the deconjugation of SUMOs from their substrate proteins. Hence, this is a promising target tackling the dysregulation of the SUMOylation process. Herein, we report the discovery of a novel protein-protein interaction (PPI) inhibitor for SENP1-SUMO1 by virtual screening and subsequent medicinal chemistry optimization of the hit molecule. The optimized inhibitor ZHAWOC8697 showed IC50 values of 8.6 µM against SENP1 and 2.3 µM against SENP2. With a photo affinity probe the SENP target was validated. This novel SENP inhibitor represents a new valuable tool for the study of SUMOylation processes and the SENP-associated development of small molecule-based treatment options.


Assuntos
Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina , Sumoilação , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo , Piruvatos , Endopeptidases/metabolismo , Peptídeo Hidrolases/metabolismo
5.
Biomacromolecules ; 22(2): 629-639, 2021 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-33347749

RESUMO

Matrix metalloproteinase 9 (MMP-9) has a key role in many biological processes, and while it is crucial for a normal immune response, excessive release of this enzyme can lead to severe tissue damage, as evidenced by proteolytic digestion and perforation of the cornea during infectious keratitis. Current medical management strategies for keratitis mostly focus on antibacterial effects, but largely neglect the role of excess MMP activity. Here, a cyclic tissue inhibitor of metalloproteinase (TIMP) peptidomimetic, which downregulated MMP-9 expression both at the mRNA and protein levels as well as MMP-9 activity in THP-1-derived macrophages, is reported. A similar downregulating effect could also be observed on α smooth muscle actin (α-SMA) expression in fibroblasts. Furthermore, the TIMP peptidomimetic reduced Pseudomonas aeruginosa-induced MMP-9 activity in an ex vivo porcine infectious keratitis model and histological examinations demonstrated that a decrease of corneal thickness, associated with keratitis progression, was inhibited upon peptidomimetic treatment. The presented approach to reduce MMP-9 activity thus holds great potential to decrease corneal tissue damage and improve the clinical success of current treatment strategies for infectious keratitis.


Assuntos
Ceratite , Peptidomiméticos , Animais , Ceratite/tratamento farmacológico , Metaloproteinase 2 da Matriz , Peptidomiméticos/farmacologia , Suínos , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidores Teciduais de Metaloproteinases
6.
Angew Chem Int Ed Engl ; 60(28): 15613-15621, 2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-33730410

RESUMO

Leucinostatin A is one of the most potent antiprotozoal compounds ever described, but little was known on structure-activity relationships (SAR). We used Trypanosoma brucei as a protozoal model organism to test synthetically modified derivatives, resulting in simplified but equally active compounds 2 (ZHAWOC6025) and 4 (ZHAWOC6027), which were subsequently modified in all regions of the molecule to gain an in-depth SAR understanding. The antiprotozoal SAR matched SAR in phospholipid liposomes, where membrane integrity, leaking, and dynamics were studied. The mode of action is discussed based on a structure-activity analysis of derivatives in efficacy, ultrastructural studies in T. brucei, and artificial membrane models, mimicking membrane stability and membrane potential. The main site of antiprotozoal action of natural and synthetic leucinostatins lies in the destabilization of the inner mitochondrial membrane, as demonstrated by ultrastructural analysis, electron microscopy and mitochondrial staining. Long-time sublethal exposure of T. brucei (200 passages) and siRNA screening of 12'000 mutants showed no signs of resistance development to the synthetic derivatives.


Assuntos
Peptídeos Catiônicos Antimicrobianos/farmacologia , Antiprotozoários/farmacologia , Trypanosoma brucei brucei/efeitos dos fármacos , Peptídeos Catiônicos Antimicrobianos/síntese química , Peptídeos Catiônicos Antimicrobianos/química , Antiprotozoários/síntese química , Antiprotozoários/química , Conformação Molecular , Testes de Sensibilidade Parasitária , Relação Estrutura-Atividade , Trypanosoma brucei brucei/genética
7.
Chimia (Aarau) ; 74(5): 382-390, 2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32482215

RESUMO

Actinomycetes strains isolated from different habitats in Switzerland were investigated for production of antibacterial and antitumoral compounds. Based on partial 16S rRNA gene sequences, the isolated strains were identified to genus level. Streptomyces as the largest genus of Actinobacteriawas isolated the most frequently. A screening assay using the OmniLog instrument was established to facilitate the detection of active compounds from actinomycetes. Extracts prepared from the cultivated strains able to inhibit Staphylococcus aureusand Escherichia coliwere further analysed by HPLC and MALDI-TOF MS to identify the produced antibiotics. In this study, the bioactive compound echinomycin was identified from two isolated Streptomycesstrains. Natural compounds similar to TPU-0037-C, azalomycin F4a 2-ethylpentyl ester, a derivative of bafilomycin A1, milbemycin-α8 and dihydropicromycin were detected from different isolated Streptomyces strains. Milbemycin-α8 showed cytotoxic activity against HT-29 colon cancer cells. The rare actinomycete,Micromonospora sp. Stup16_C148 produced a compound that matches with the antibiotic bottromycin A2. The draft genome sequence from Actinokineospora strain B136.1 was determined using Illumina and nanopore-based technologies. The isolated strain was not able to produce antibacterial compounds under standard cultivation conditions. The antiSMASH bioinformatics analyses of the genome from strain B136.1 identified biosynthetic gene clusters with identity values between 4% to 90% to known gene clusters encoding antibiotics. The combinations of cultivation conditions, screening assays, analytical methods and genome mining are important tools to characterize strains of actinomycetes for the identification of their potential to produce natural compounds with antimicrobial activity.


Assuntos
Actinobacteria , RNA Ribossômico 16S , Streptomyces , Suíça
8.
Chemistry ; 25(34): 7960-7980, 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-30720221

RESUMO

Matrix metalloproteinases (MMPs) are involved in a multitude of severe diseases. Despite MMPs being considered druggable targets, past drug-discovery programs have not delivered the anticipated clinical benefits. This review examines the latest structural evolution of small-molecule inhibitors of MMPs, with a focus on the development of novel chemical entities with improved affinity and selectivity profiles. X-ray crystallographic data of the protein targets and cocrystal structures with inhibitors proved to be key for the success achieved during this ambitious endeavor. An evolutionary view on the structural diversity generated for this class of molecules is provided. This encouraging development paves the way for the clinical utilization of this class of highly relevant therapeutic targets. The structure-based design of superior MMP inhibitors highlights the power of this technique and displays strategies for the development of treatment options based on the modulation of challenging drug targets.


Assuntos
Desenho de Fármacos , Inibidores de Metaloproteinases de Matriz/química , Inibidores de Metaloproteinases de Matriz/farmacologia , Animais , Descoberta de Drogas/métodos , Humanos , Metaloproteinases da Matriz/química , Metaloproteinases da Matriz/metabolismo , Modelos Moleculares , Relação Estrutura-Atividade
10.
Molecules ; 24(12)2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31216704

RESUMO

The family of matrix metalloproteinases (MMPs) consists of a set of biological targets that are involved in a multitude of severe pathogenic events such as different forms of cancers or arthritis. Modulation of the target class with small molecule drugs has not led to the anticipated success until present, as all clinical trials failed due to unacceptable side effects or a lack of therapeutic outcome. Monoclonal antibodies offer a tremendous therapeutic potential given their high target selectivity and good pharmacokinetic profiles. For the treatment of a variety of diseases there are already antibody therapies available and the number is increasing. Recently, several antibodies were developed for the selective inhibition of single MMPs that showed high potency and were therefore investigated in in vivo studies with promising results. In this review, we highlight the progress that has been achieved toward the design of inhibitory antibodies that successfully modulate MMP-9 and MMP-14.


Assuntos
Anticorpos Monoclonais/química , Anticorpos Monoclonais/farmacologia , Desenho de Fármacos , Inibidores de Metaloproteinases de Matriz/química , Inibidores de Metaloproteinases de Matriz/farmacologia , Metaloproteinases da Matriz/química , Sequência de Aminoácidos , Animais , Sítios de Ligação , Humanos , Metaloproteinases da Matriz/classificação , Conformação Molecular , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Ligação Proteica , Relação Estrutura-Atividade
11.
Molecules ; 24(7)2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30987252

RESUMO

Structure-based design and synthesis of two biphenyl-N-acyl-ß-d-glucopyranosylamine derivatives as well as their assessment as inhibitors of human liver glycogen phosphorylase (hlGPa, a pharmaceutical target for type 2 diabetes) is presented. X-ray crystallography revealed the importance of structural water molecules and that the inhibitory efficacy correlates with the degree of disturbance caused by the inhibitor binding to a loop crucial for the catalytic mechanism. The in silico-derived models of the binding mode generated during the design process corresponded very well with the crystallographic data.


Assuntos
Desenho de Fármacos , Inibidores Enzimáticos/química , Glucosamina/análogos & derivados , Glicogênio Fosforilase/química , Relação Quantitativa Estrutura-Atividade , Sítios de Ligação , Domínio Catalítico , Técnicas de Química Sintética , Cristalografia por Raios X , Inibidores Enzimáticos/farmacologia , Glucosamina/síntese química , Glucosamina/química , Glucosamina/farmacologia , Glicogênio Fosforilase/antagonistas & inibidores , Humanos , Ligação de Hidrogênio , Modelos Moleculares , Ligação Proteica
12.
Angew Chem Int Ed Engl ; 58(11): 3300-3345, 2019 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-29846032

RESUMO

The natural phenomenon of drug resistance is a widespread issue that hampers the performance of drugs in many major clinical indications. Antibacterial and antifungal drugs are affected, as well as compounds for the treatment of cancer, viral infections, or parasitic diseases. Despite the very diverse set of biological targets and organisms involved in the development of drug resistance, the underlying molecular mechanisms have been identified to understand the emergence of resistance and to overcome this detrimental process. Detailed structural information on the root causes for drug resistance is nowadays frequently available, so next-generation drugs can be designed that are anticipated to suffer less from resistance. This knowledge-based approach is essential for fighting the inevitable occurrence of drug resistance.


Assuntos
Fármacos Anti-HIV/química , Anti-Infecciosos/química , Antimaláricos/química , Antineoplásicos/química , Resistência a Medicamentos/efeitos dos fármacos , Animais , Fármacos Anti-HIV/farmacologia , Anti-Infecciosos/farmacologia , Antimaláricos/farmacologia , Antineoplásicos/farmacologia , Desenho de Fármacos , Humanos , Modelos Moleculares , Estrutura Molecular , Ligação Proteica , Transdução de Sinais , Relação Estrutura-Atividade
13.
Angew Chem Int Ed Engl ; 58(12): 4051-4055, 2019 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-30615822

RESUMO

De novo drug discovery is still a challenge in the search for potent and selective modulators of therapeutically relevant target proteins. Here, we disclose the unexpected discovery of a peptidic ligand 1 by X-ray crystallography, which was auto-tailored by the therapeutic target MMP-13 through partial self-degradation and subsequent structure-based optimization to a highly potent and selective ß-sheet peptidomimetic inhibitor derived from the endogenous tissue inhibitors of metalloproteinases (TIMPs). The incorporation of non-proteinogenic amino acids in combination with a cyclization strategy proved to be key for the de novo design of TIMP peptidomimetics. The optimized cyclic peptide 4 (ZHAWOC7726) is membrane permeable with an IC50 of 21 nm for MMP-13 and an attractive selectivity profile with respect to a polypharmacology approach including the anticancer targets MMP-2 (IC50 : 170 nm) and MMP-9 (IC50 : 140 nm).


Assuntos
Desenho de Fármacos , Inibidores de Proteases/química , Sítios de Ligação , Cristalografia por Raios X , Ciclização , Metaloproteinase 13 da Matriz/química , Metaloproteinase 13 da Matriz/metabolismo , Inibidores de Metaloproteinases de Matriz/síntese química , Inibidores de Metaloproteinases de Matriz/química , Inibidores de Metaloproteinases de Matriz/metabolismo , Simulação de Dinâmica Molecular , Peptídeos Cíclicos/química , Peptídeos Cíclicos/metabolismo , Peptidomiméticos , Inibidores de Proteases/síntese química , Inibidores de Proteases/metabolismo , Inibidores Teciduais de Metaloproteinases/química
14.
Molecules ; 22(9)2017 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32961647

RESUMO

Matrix metalloproteinase 7 (MMP-7) is a member of the MMP superfamily and is able to degrade extracellular matrix proteins such as casein, gelatin, fibronectin and proteoglycan. MMP-7 is a validated target for the development of small molecule drugs against cancer. MMP-13 is within the enzyme class the most efficient contributor to type II collagen degeneration and is a validated target in arthritis and cancer. We have developed the dual MMP-7/-13 inhibitor ZHAWOC6941 with IC50-values of 2.2 µM (MMP-7) and 1.2 µM (MMP-13) that is selective over a broad range of MMP isoforms. It spares MMP-1, -2, -3, -8, -9, -12 and -14, making it a valuable modulator for targeted polypharmacology approaches.

15.
Angew Chem Int Ed Engl ; 56(43): 13184-13186, 2017 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-28895263

RESUMO

Seek, and ye shall find: After years of focusing research on synthetic antibiotics out of fear that all the useful natural ones had already been found, a novel antibacterial compound has been discovered through conventional microbial extract screening. The broad-spectrum nucleoside-analogue inhibitor pseudouridimycin is selective for bacterial RNA polymerase and elicits very low resistance rates.


Assuntos
Antibacterianos/metabolismo , Bactérias/enzimologia , Proteínas de Bactérias/metabolismo , RNA Polimerases Dirigidas por DNA/metabolismo , Nucleosídeos/análogos & derivados , Antibacterianos/química , Antibacterianos/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , RNA Polimerases Dirigidas por DNA/antagonistas & inibidores , Bactérias Gram-Negativas/efeitos dos fármacos , Nucleosídeos/química , Nucleosídeos/metabolismo , Nucleosídeos/farmacologia , Relação Estrutura-Atividade
16.
Int J Mol Sci ; 17(3): 314, 2016 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-26938528

RESUMO

Matrix metalloproteinases (MMPs) are a class of zinc dependent endopeptidases which play a crucial role in a multitude of severe diseases such as cancer and osteoarthritis. We employed MMP-13 as the target enzyme for the structure-based design and synthesis of inhibitors able to recognize the catalytic zinc ion in addition to an allosteric binding site in order to increase the affinity of the ligand. Guided by molecular modeling, we optimized an initial allosteric inhibitor by addition of linker fragments and weak zinc binders for recognition of the catalytic center. Furthermore we improved the lipophilic ligand efficiency (LLE) of the initial inhibitor by adding appropriate zinc binding fragments to lower the clogP values of the inhibitors, while maintaining their potency. All synthesized inhibitors showed elevated affinity compared to the initial hit, also most of the novel inhibitors displayed better LLE. Derivatives with carboxylic acids as the zinc binding fragments turned out to be the most potent inhibitors (compound 3 (ZHAWOC5077): IC50 = 134 nM) whereas acyl sulfonamides showed the best lipophilic ligand efficiencies (compound 18 (ZHAWOC5135): LLE = 2.91).


Assuntos
Desenho de Fármacos , Metaloproteinase 13 da Matriz/metabolismo , Inibidores de Metaloproteinases de Matriz/química , Inibidores de Metaloproteinases de Matriz/farmacologia , Zinco/metabolismo , Sítio Alostérico/efeitos dos fármacos , Ácidos Carboxílicos/química , Ácidos Carboxílicos/farmacologia , Humanos , Ligantes , Metaloproteinase 13 da Matriz/química , Simulação de Acoplamento Molecular , Sulfonamidas/química , Sulfonamidas/farmacologia , Zinco/química
17.
Angew Chem Int Ed Engl ; 55(23): 6600-26, 2016 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-27000559

RESUMO

Finding strategies against the development of antibiotic resistance is a major global challenge for the life sciences community and for public health. The past decades have seen a dramatic worldwide increase in human-pathogenic bacteria that are resistant to one or multiple antibiotics. More and more infections caused by resistant microorganisms fail to respond to conventional treatment, and in some cases, even last-resort antibiotics have lost their power. In addition, industry pipelines for the development of novel antibiotics have run dry over the past decades. A recent world health day by the World Health Organization titled "Combat drug resistance: no action today means no cure tomorrow" triggered an increase in research activity, and several promising strategies have been developed to restore treatment options against infections by resistant bacterial pathogens.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Antibacterianos/química , Bactérias/metabolismo , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/biossíntese , Desenho de Fármacos , Macrolídeos/química , Macrolídeos/farmacologia , Simulação de Dinâmica Molecular , Organofosfatos/química , Organofosfatos/farmacologia , Oxazóis/química , Oxazóis/farmacologia , Oxazolidinonas/química , Oxazolidinonas/farmacologia , Relação Estrutura-Atividade
18.
Drug Discov Today ; 29(11): 104178, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39276920

RESUMO

Targeted protein degradation (TPD) has revolutionized drug discovery by selectively eliminating specific proteins within and outside the cellular context. Over the past two decades, TPD has expanded its focus beyond well-established targets, exploring diverse proteins beyond cancer-related ones. This evolution extends the potential of TPD to various diseases. Notably, TPD can target proteins at demanding locations, such as the extracellular matrix (ECM) and cellular membranes, presenting both opportunities and challenges for future research. In this review, we comprehensively examine the exciting opportunities in the burgeoning field of TPD, highlighting different targets, their cellular environment, and innovative strategies for modern drug discovery.

19.
Chimia (Aarau) ; 66(3): 132-4, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22546259

RESUMO

We report the development of a powerful data management tool for chemical and biological data: CyBy(2). CyBy(2) is a structure-based information management tool used to store and visualize structural data alongside additional information such as project assignment, physical information, spectroscopic data, biological activity, functional data and synthetic procedures. The application consists of a database, an application server, used to query and update the database, and a client application with a rich graphical user interface (GUI) used to interact with the server.


Assuntos
Sistemas de Gerenciamento de Base de Dados , Design de Software , Interface Usuário-Computador , Biologia/métodos , Química/métodos
20.
Drug Discov Today ; 27(2): 567-575, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34678490

RESUMO

Given the vast number of venomous and poisonous animals, it is surprising that only relatively few animal-derived toxins have been explored and made their way into marketed drugs or are being investigated in ongoing clinical trials. In this review, we highlight marketed drugs deriving from animal toxins as well as ongoing clinical trials and preclinical investigations in the field. We emphasize that more attention should be paid to the rich supply of candidates that nature provides as valuable starting points for addressing serious unmet medical needs.


Assuntos
Toxinas Biológicas , Peçonhas , Animais , Toxinas Biológicas/uso terapêutico , Peçonhas/uso terapêutico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA