Targeting Peptides: The New Generation of Targeted Drug Delivery Systems

Pharmaceutics, Год журнала: 2023, Номер 15(6), С. 1648 - 1648

Опубликована: Июнь 3, 2023

Peptides can act as targeting molecules, analogously to oligonucleotide aptamers and antibodies. They are particularly efficient in terms of production stability physiological environments; recent years, they have been increasingly studied agents for several diseases, from tumors central nervous system disorders, also thanks the ability some them cross blood–brain barrier. In this review, we will describe techniques employed their experimental silico design, well possible applications. We discuss advancements formulation chemical modifications that make even more stable effective. Finally, how use could effectively help overcome various problems improve existing treatments.

Язык: Английский

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Leveraging Marine Predators Algorithm with Deep Learning for Lung and Colon Cancer Diagnosis

Cancers, Год журнала: 2023, Номер 15(5), С. 1591 - 1591

Опубликована: Март 3, 2023

Cancer is a deadly disease caused by various biochemical abnormalities and genetic diseases. Colon lung cancer have developed as two major causes of disability death in human beings. The histopathological detection these malignancies vital element determining the optimal solution. Timely initial diagnosis sickness on either front diminishes possibility death. Deep learning (DL) machine (ML) methods are used to hasten such recognition, allowing research community examine more patients much shorter period at less cost. This study introduces marine predator's algorithm with deep colon classification (MPADL-LC3) technique. presented MPADL-LC3 technique aims properly discriminate different types images. To accomplish this, employs CLAHE-based contrast enhancement pre-processing step. In addition, applies MobileNet derive feature vector generation. Meanwhile, MPA hyperparameter optimizer. Furthermore, belief networks (DBN) can be applied for color classification. simulation values were examined benchmark datasets. comparison highlighted enhanced outcomes system terms measures.

Язык: Английский

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RAS‐targeted cancer therapy: Advances in drugging specific mutations

MedComm, Год журнала: 2023, Номер 4(3)

Опубликована: Май 27, 2023

Rat sarcoma (RAS), as a frequently mutated oncogene, has been studied an attractive target for treating RAS-driven cancers over four decades. However, it is until the recent success of kirsten-RAS (KRAS)

Язык: Английский

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In silico mutagenesis-based designing of oncogenic SHP2 peptide to inhibit cancer progression

Scientific Reports, Год журнала: 2023, Номер 13(1)

Опубликована: Июнь 21, 2023

Abstract Cancer is among the top causes of death, accounting for an estimated 9.6 million deaths in 2018, it appeared that approximately 500,000 people die from cancer United States alone annually. The SHP2 plays a major role regulation cell growth, proliferation, and differentiation, functional upregulation this enzyme linked to oncogenesis developmental disorders. activity has been several types which no drugs are currently available. In our study, we aimed design peptide inhibitors against mutant. crystal structure human Src SH2-PQpYEEIPI mutant was downloaded protein databank. We generated peptides native wild using silico mutagenesis method, showed changes (P302W, Y304F, E306Q, Q303A) might boost peptide's affinity binding SHP2. Furthermore, dynamical stability affinities mutated were confirmed Molecular dynamics simulation Mechanics with Generalized Born Surface Area Solvation free energy calculations. proposed substitution greatly enhanced at residue level, according study decomposed into its component residues. Our may prevent spread by inhibiting SHP2, detailed analyses affinities.

Язык: Английский

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In-Silico Lead Druggable Compounds Identification against SARS COVID-19 Main Protease Target from In-House, Chembridge and Zinc Databases by Structure-Based Virtual Screening, Molecular Docking and Molecular Dynamics Simulations

Bioengineering, Год журнала: 2023, Номер 10(1), С. 100 - 100

Опубликована: Янв. 11, 2023

Pharmacological strategies to lower the viral load among patients suffering from severe diseases were researched in great detail during SARS-CoV-2 outbreak. The protease Mpro (3CLpro) is necessary for replication and main therapeutic targets proposed, thus far. To stop pandemic spreading, researchers are working find more effective inhibitors against SARS-CoV-2. 33.8 kDa of SARS-CoV-2, being a nonhuman homologue, has possibility utilized as target coronaviruses. develop drug-like compounds capable preventing SARS-main CoV-2's (Mpro), computer-aided drug design (CADD) approach extremely viable. Using MOE, structure-based virtual screening (SBVS) in-house commercial databases was carried out using proteins. most promising hits obtained (VS) put through molecular docking with help MOE. yielded 3/5 (in-house database) 56/66 (commercial databases). Finally, database), (ZINC 2/7 (ChemBridge chosen potent lead various scaffolds due their considerable binding affinity protein. outcomes SBVS then validated an analysis based on dynamics simulation (MDS). complexes' stability tested MDS post-MDS. candidates found exhibit high capacity fitting into protein-binding pocket interacting catalytic dyad. At least one selected will possibly prove useful future research. However, further scientific confirmation form preclinical clinical research required before implementation.

Язык: Английский

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Network pharmacology, molecular simulation, and binding free energy calculation-based investigation of Neosetophomone B revealed key targets for the treatment of cancer

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Фев. 15, 2024

In the current study, Neosetophomone B (NSP–B) was investigated for its anti-cancerous potential using network pharmacology, quantum polarized ligand docking, molecular simulation, and binding free energy calculation. Using SwissTarget prediction, Superpred, targets NSP-B were predicted while cancer-associated genes obtained from DisGeNet. Among total proteins, only 25 reported to overlap with disease-associated genes. A protein-protein interaction constructed by Cytoscape STRING databases. MCODE used detect densely connected subnetworks which revealed three sub-clusters. Cytohubba four targets, i.e., fibroblast growth factor , FGF20, FGF22, FGF23 as hub Molecular docking of based on a quantum-polarized approach FGF6, stronger interactions key hotspot residues. Moreover, simulation stable dynamic behavior, good structural packing, residues’ flexibility each complex. Hydrogen bonding in complex also observed be above minimum. addition, calculated MM/GBSA (Molecular Mechanics/Generalized Born Surface Area) MM/PBSA Mechanics/Poisson-Boltzmann approaches. The values −36.85 kcal/mol FGF6-NSP-B complex, −43.87 FGF20-NSP-B −37.42 FGF22-NSP-B −41.91 FGF23-NSP-B showed −30.05 −39.62 −34.89 −37.18 These findings underscore promising against FGF23, are essential cancer signaling. results significantly bolster candidate therapy.

Язык: Английский

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Phyto-fabrication of ultrafine nanoscale holmium oxide HT-Ho₂O₃ NPs and their biomedical potential

RSC Advances, Год журнала: 2023, Номер 13(40), С. 27912 - 27922

Опубликована: Янв. 1, 2023

In this study holmium oxide nanoparticles (Ho 2 O 3 NPs) are fabricated using Hyphaene thebaica extracts as a bioreductant.

Язык: Английский

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Structural insights, regulation, and recent advances of RAS inhibitors in the MAPK signaling cascade: a medicinal chemistry perspective

RSC Medicinal Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

The MAPK pathway has four main components: RAS, RAF, MEK, and ERK. Among these, RAS is the most frequently mutated protein leading cause of cancer. three isoforms gene are HRAS, NRAS, KRAS. KRAS characterized by two splice variants, K-Ras4A K-Ras4B. occurrence cancer often involves a mutation in both KRAS4A KRAS4B. In this study, we have elucidated mechanism complex movement switches I II. Only inhibitors, sotorasib adagrasib, been approved FDA, several clinical trials. This review comprises recent developments synthetic their unique properties, importance inhibiting mutations, current challenges developing new inhibitors. will undoubtedly help researchers design novel

Язык: Английский

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Evolution of computational techniques against various KRAS mutants in search for therapeutic drugs: a review article

Cancer Chemotherapy and Pharmacology, Год журнала: 2025, Номер 95(1)

Опубликована: Апрель 7, 2025

Язык: Английский

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Medicinal Phytocompounds as Potential Inhibitors of p300-HIF1α Interaction: A Structure-Based Screening and Molecular Dynamics Simulation Study

Pharmaceuticals, Год журнала: 2025, Номер 18(4), С. 602 - 602

Опубликована: Апрель 21, 2025

Background: Hypoxia plays a key role in cancer progression, mainly by stabilizing and activating hypoxia-inducible factor-1 (HIF-1). For HIF-1 to function under low oxygen conditions, it must interact with the transcriptional coactivator p300, critical step for promoting cell survival adaptation hypoxic environments. Methods: Consequently, we used drug design molecular simulation techniques screen phytochemical databases, including traditional Chinese African medicine sources, compounds that could disrupt p300/HIF-1 interaction. Results: In this study, identified potential high docking scores such as EA-176920 (−8.719), EA-46881231 (−8.642), SA-31161 (−9.580), SA-5280863 (−8.179), NE-5280362 (−10.287), NE-72276 (−9.017), NA-11210533 (−10.366), NA-11336960 (−7.818), TCM-5281792 (−12.648), TCM-6441280 (−9.470 kcal/mol) lead compounds. Furthermore, compound highest score from each database (EA-176920, SA-31161, NE-5280362, NA-11210533, TCM-5281792) was subjected further analysis. The stable binding affinity of these p300 confirmed Post-simulation free energy (−22.0020 kcal/mol, −25.4499 −32.4530 −33.9918 −57.7755 respectively) KD Moreover, selected followed Lipinski rules favorable ADMET properties like efficient intestinal absorption, water solubility, no toxicity. Conclusions: Our findings highlight natural target protein–protein interactions lay groundwork future vitro vivo studies explore their therapeutic potential. Specifically, disrupting interaction interfere hypoxia-driven pathways promote tumor growth, angiogenesis, metastasis, offering promising strategy suppress progression at level.

Язык: Английский

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