The increasing human population, combined with low inefficiency and adverse effects of available pesticides, has magnified the urgent need of developing next-generation pesticides. Among the available approaches, strategies targeting invertebrate G protein-coupled receptors (GPCRs) are very promising as these receptors are the targets of endogenous neuropeptides/neuromodulators that upon binding to their receptors induce profound changes in insect physiology. Therefore, exploring GPCR regulators has great potential in the development of targeted next-generation pesticides. Despite the great potential of such alternative pesticides, so far there has been only one approved compound, Amitraz, which conveys its antipest activity via the GPCR Octopamine receptor. Here, we review the current status of pesticide development, hazards associated with conventional pesticide compounds, alternative strategies that involve next-generation of pesticides, structural features of GPCRs, and opportunities and challenges of targeting the members of this superfamily in invertebrates to develop anti-pest agents. In conclusion, we emphasize that the potential of GPCRs cannot be utilized in full without more genomic and transcriptomic data to improve our understanding of the complex network of peptidergic signaling pathways. We argue how vital it is to obtain three-dimensional (3D) structural data on physiologically important target GPCRs and encourage the readers to use the state of the art in silico methods such as virtual screening for the discovery of new pesticide compounds.
Kanser immünoterapisi, kanserle mücadelede insan immün sistemini güçlendirmeyi amaçlar ve immün sistemin kanser ile normal hücreler arasındaki en iyi biyokimyasal farklılıkları tespit etme yeteneğine dayanır. İmmünoterapi; özgüllüğü, uzun süreli etkileri ve iyileşmeye olan katkıları sayesinde, kanser tedavisindeki yerini sağlamlaştırmaya devam etmektedir. Tümörler, anti-tümör immün tepkilerini inhibe etmek için bağışıklık kontrol noktaları olarak da bilinen inhibitör reseptörleri kullanır. Birçok kişide immün-baskılamaya, Sitotoksik T-Lenfosit-İlişkili Antijen-4 (CTLA-4) ve Programlanmış Ölüm-1 (PD-1) reseptörleri aracılık eder. CTLA-4 ve/veya PD-1 kontrol noktası inhibitörlerini hedefleyen monoklonal antikor (mAb) temelli terapilerin, birçok farklı malignin türünde, hastalara gözle görülür yararlar sağladığı gözlemlenmiştir. Bu çalışmanın amacı, CTLA-4 ve PD-1/ PD-L1 tedavilerinin kanser tedavisindeki ve immünoterapideki yeri ile ilgili bilimsel çalışmaları incelemektir.
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