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1.
Drug Discov Today ; 29(6): 104009, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38692505

RESUMO

AI techniques are making inroads into the field of drug discovery. As a result, a growing number of drugs and vaccines have been discovered using AI. However, questions remain about the success of these molecules in clinical trials. To address these questions, we conducted a first analysis of the clinical pipelines of AI-native Biotech companies. In Phase I we find AI-discovered molecules have an 80-90% success rate, substantially higher than historic industry averages. This suggests, we argue, that AI is highly capable of designing or identifying molecules with drug-like properties. In Phase II the success rate is ∼40%, albeit on a limited sample size, comparable to historic industry averages. Our findings highlight early signs of the clinical potential of AI-discovered molecules.


Assuntos
Inteligência Artificial , Ensaios Clínicos como Assunto , Descoberta de Drogas , Humanos , Ensaios Clínicos como Assunto/métodos , Descoberta de Drogas/métodos , Indústria Farmacêutica
3.
Cell Rep ; 19(4): 836-848, 2017 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-28445733

RESUMO

During aging, innate immunity progresses to a chronically active state. However, what distinguishes those that "age well" from those developing age-related neurological conditions is unclear. We used Drosophila to explore the cost of immunity in the aging brain. We show that mutations in intracellular negative regulators of the IMD/NF-κB pathway predisposed flies to toxic levels of antimicrobial peptides, resulting in early locomotor defects, extensive neurodegeneration, and reduced lifespan. These phenotypes were rescued when immunity was suppressed in glia. In healthy flies, suppressing immunity in glial cells resulted in increased adipokinetic hormonal signaling with high nutrient levels in later life and an extension of active lifespan. Thus, when levels of IMD/NF-κB deviate from normal, two mechanisms are at play: lower levels derepress an immune-endocrine axis, which mobilizes nutrients, leading to lifespan extension, whereas higher levels increase antimicrobial peptides, causing neurodegeneration. Immunity in the fly brain is therefore a key lifespan determinant.


Assuntos
Envelhecimento , Encéfalo/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila/metabolismo , Imunidade Inata , NF-kappa B/metabolismo , Animais , Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/metabolismo , Proteínas de Drosophila/antagonistas & inibidores , Proteínas de Drosophila/genética , Glicopeptídeos/genética , Glicopeptídeos/metabolismo , Hormônios de Inseto/genética , Hormônios de Inseto/metabolismo , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Longevidade , Doenças Neurodegenerativas/mortalidade , Doenças Neurodegenerativas/patologia , Doenças Neurodegenerativas/veterinária , Neuroglia/metabolismo , Oligopeptídeos/genética , Oligopeptídeos/metabolismo , Ácido Pirrolidonocarboxílico/análogos & derivados , Ácido Pirrolidonocarboxílico/metabolismo , Interferência de RNA , RNA Mensageiro/metabolismo , Transdução de Sinais , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
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