Current status of nucleic acid therapy and its new progress in cancer treatment DOI Creative Commons

Wenting Lou,

Leqi Zhang,

Jianwei Wang

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 142, P. 113157 - 113157

Published: Sept. 16, 2024

Nucleic acid is an essential biopolymer in all living cells, performing the functions of storing and transmitting genetic information synthesizing protein. In recent decades, with progress science biotechnology continuous exploration performed by nucleic acid, more studies have confirmed that therapy for organisms has great medical therapeutic potential. drugs began to become independent agents. As a new method, plays important role treatment diseases, viral infections cancers. There are currently 19 approved Food Drug Administration (FDA). following review, we start from principles advantages therapy, briefly describe development history drugs. And then give examples various RNA drugs, including antisense oligonucleotides (ASO), mRNA vaccines, small interfering (siRNA) microRNA (miRNA), aptamers, activating (saRNA). addition, also focused on current status used cancer breakthrough years. Clinical trials under way, conventional radiotherapy chemotherapy combined immunotherapies such as checkpoint inhibitors may be main prospects successful treatment.

Language: Английский

Progress of machine learning in the application of small molecule druggability prediction DOI
Junyao Li, Jianmei Zhang, Rui Guo

et al.

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 285, P. 117269 - 117269

Published: Jan. 10, 2025

Language: Английский

Citations

2
Quinolizidine-Type Alkaloids: Chemodiversity, Occurrence, and Bioactivity DOI Creative Commons
W Cely-Veloza, Massuo J. Kato, Ericsson Coy‐Barrera

et al.

ACS Omega, Journal Year: 2023, Volume and Issue: 8(31), P. 27862 - 27893

Published: July 28, 2023

Quinolizidine alkaloids (QAs) are nitrogen-containing compounds produced naturally as specialized metabolites distributed in plants and animals (e.g., frogs, sponges). The present review compiles the available information on chemical diversity biological activity of QAs reported during last three decades. So far, 397 have been isolated, gathering 20 different representative classes, including most common such matrine (13.6%), lupanine (9.8%), anagyrine (4.0%), sparteine (5.3%), cytisine (6.5%), tetrahydrocytisine (4.3%), lupinine (12.1%), macrocyclic bisquinolizidine (9.3%), biphenylquinolizidine lactone (7.1%), dimeric other less known (20.9%), which include several structural patterns QAs. A detailed survey about bioactivities these indicated their potential cytotoxic, antiviral, antimicrobial, insecticidal, anti-inflammatory, antimalarial, antiacetylcholinesterase compounds, involving favorable putative drug-likeness scores. In this regard, research progress biological/pharmacological requires further studies oriented expanding space to find bioactive scaffolds based for pharmacological agrochemical applications.

Language: Английский

Citations

33
Recent updates in nanoscale delivery systems of platinum(IV) antitumor prodrugs DOI
Zhiyuan Zhou,

Pengmin Shi,

Changli Wang

et al.

Coordination Chemistry Reviews, Journal Year: 2024, Volume and Issue: 508, P. 215774 - 215774

Published: March 18, 2024

Language: Английский

Citations

13
Dissolution Mechanisms of Amorphous Solid Dispersions: Application of Ternary Phase Diagrams To Explain Release Behavior DOI
Alexandru Deac, Christian Luebbert, Qingqing Qi

et al.

Molecular Pharmaceutics, Journal Year: 2024, Volume and Issue: 21(4), P. 1900 - 1918

Published: March 12, 2024

The use of amorphous solid dispersions (ASDs) in commercial drug products has increased recent years due to the large number poorly soluble drugs pharmaceutical pipeline. However, release behavior ASDs is complex and remains not well understood. Often, from rapid complete at lower loadings (DLs) but becomes slow incomplete higher DLs. DL where hindered termed limit congruency (LoC). Currently, there are no approaches predict LoC. findings show that one potential cause leading LoC a change phase morphology after water-induced separation ASD/solution interface. In this study, contact with aqueous solutions was described thermodynamically by constructing experimental computational ternary diagrams, these were used changes ultimately Experimental diagrams obtained equilibrating ASD/water mixtures over time. Computational Perturbed Chain Statistical Associating Fluid Theory (PC-SAFT). hydrophobic studied fluorescence confocal microscopy. It demonstrated critical point (plait point) composition approximately corresponded ASD DL, phase, formed during separation, became interconnected release. This work provides mechanistic insights into highlights silico design using diagrams.

Language: Английский

Citations

10
Antimicrobial potentials of Pandanus amaryllifolius Roxb.: Phytochemical profiling, antioxidant, and molecular docking studies DOI Creative Commons
Dwi Kusuma Wahyuni,

Gita Aqila Nuha,

Tope Gafar Atere

et al.

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(8), P. e0305348 - e0305348

Published: Aug. 14, 2024

The emergence of antimicrobial resistance has led to an urgent need for novel drugs. This study aimed determine the antioxidant and potentials in silico vitro Pandanus amaryllifolius Roxb. ethanolic extract. extracts were subjected gas chromatography-mass spectrometry (GC-MS) analysis identify compounds. In studies performed gain insights into possible mechanism action active compounds as antimicrobials. activities assessed using agar well diffusion method against Surabaya strain Escherichia coli Staphylococcus aureus . Antioxidant properties extract done DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) ABTS [2,2’-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid)] inhibition assays. phytochemical screening revealed that high flavonoids polyphenols contents. GC-MS detected presence 52 bioactive substances, with n -hexadecanoic acid, 9, 12, 15-octadecatrienoic benzofuran 2,3-dihydro-. quinic neophytadiene major compound. Molecular docking showed these have a binding affinity towards target proteins, thereby inhibiting their activities. P exhibited IC 50 11.96 ± 4.01 μg/ml 26.18 7.44 ABTS. diameters zones (DIZ) percentage (PI) calculated varied every single pathogen 16.44 1.21mm/66.76 4.92% (50%) 21.22 0.11mm/82.49 3.91% E S (DIZ/PI) respectively. Overall, this provides information on responsible natural antimicrobe lays foundation further isolate characterize candidates.

Language: Английский

Citations

10
Application of an Interdisciplinary Approach to Form Selection in Drug Development DOI
Darren L. Reid,

Margaret M. Faul,

Vilmalí López-Mejías

et al.

Organic Process Research & Development, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 25, 2025

Language: Английский

Citations

1
Leveraging efficiency metrics for the optimization of CELMoDs™ as cereblon-based molecular glue degraders DOI
Lei Jia, Jennifer R. Riggs, Dahlia R. Weiss

et al.

RSC Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Efficiency metrics are useful in medicinal chemistry to track small molecule progress lead optimization (LO). Molecular glue degraders molecules that mediate targeted protein degradation by chemically inducing proximity between an E3 ligase and a target. The potency depth of important factors identifying molecular drug candidates. We developed efficiency based on both objectives. applied these retrospectively clinical degrader series, resulting the identification Golcadomide (CC-99282). This work illustrates beneficial for

Language: Английский

Citations

1
DBPP-Predictor: a novel strategy for prediction of chemical drug-likeness based on property profiles DOI Creative Commons

Yaxin Gu,

Yimeng Wang,

Keyun Zhu

et al.

Journal of Cheminformatics, Journal Year: 2024, Volume and Issue: 16(1)

Published: Jan. 5, 2024

Abstract Evaluation of chemical drug-likeness is essential for the discovery high-quality drug candidates while avoiding unwarranted biological and clinical trial costs. A candidate should have promising drug-like properties, including pharmacological activity, suitable physicochemical ADMET properties. Hence, in silico prediction has been proposed being a challenging task. Although several models developed to assess drug-likeness, they such drawbacks as sample dependence poor interpretability. In this study, we novel strategy, named DBPP-Predictor, predict based on property profile representation by integrating The results demonstrated that DBPP-Predictor exhibited considerable generalization capability with AUC (area under curve) values from 0.817 0.913 external validation sets. terms application feasibility analysis, indicated not only consistent reasonable scoring performance different data sets, but also was able guide structural optimization. Moreover, it offered new assessment perspective, without significant linear correlation existing methods. We free standalone software users make visualization their compounds interest. summary, our provided valuable tool helping identify appropriate further development.

Language: Английский

Citations

8
Tissue distribution and retention drives efficacy of rapidly clearing VHL-based PROTACs DOI Creative Commons
Donglu Zhang, Bin Ma, Peter S. Dragovich

et al.

Communications Medicine, Journal Year: 2024, Volume and Issue: 4(1)

Published: May 16, 2024

Abstract Background Proteolysis-targeting chimeras (PROTACs) are being developed for therapeutic use. However, they have poor pharmacokinetic profiles and their tissue distribution kinetics not known. Methods A typical von Hippel-Lindau tumor suppressor (VHL)—PROTAC 14 C-A947 (BRM degrader)—was synthesized its was studied by quantitative whole-body autoradiography (QWBA) excision in rats following IV dosing. Bile duct-cannulated (BDC) allowed the elucidation of vivo clearance pathways. Distribution evaluated tissues tumors mice to support PK-PD correlation. In vitro studies enabled evaluation cell uptake mechanisms retention properties. Results Here, we show that A947 quickly distributes into rat after dosing, where it accumulates is retained such as lung liver although undergoes fast from circulation. Similar uptake/retention enable growth inhibition over 2–3 weeks a cancer model. excretes bile rats. Solute carrier (SLC) transporters involved hepatocyte PROTACs. Sustained BRM protein degradation seen extensive washout supports prolonged NCI-H1944 cells. exposure pharmacodynamics inversely correlated tumors. Conclusions Plasma sampling VHL-PROTAC does represent concentrations necessary efficacy. Understanding could less frequent administration be used

Language: Английский

Citations

7
In Silico Prediction of Pharmaceutical Degradation Pathways: A Benchmarking Study Using the Software Program Zeneth DOI Creative Commons
Rachel Hemingway,

Steven W. Baertschi,

David Benstead

et al.

Organic Process Research & Development, Journal Year: 2024, Volume and Issue: 28(3), P. 674 - 692

Published: Feb. 19, 2024

Zeneth, a software application for the prediction of chemical degradation small organic molecules, incorporates knowledge base rules to predict pathways. In addition, contains property predictors that modulate predicted likelihood given product. this study, C–H bond dissociation energy (C–H BDE) predictor, which has been integrated into software, was utilized. To determine software's predictive capabilities [using its (2020.1.0 KB)], experimentally derived profiles 25 drug substances were compared Zeneth predictions. These from forced studies, including accelerated and long-term stability aligned with International Council Harmonisation (ICH) guidelines. two case studies highlighting how data can be utilized confirm experimental or assist identification unknown products have presented. The specificity results evaluated; transformation types often not observed identified, an assessment causes is sensitivity study group also evaluated using historic (2012.2.0 KB), enabling improved over period; comparison demonstrated 40% increase in sensitivity. This ongoing expansion optimization silico tools continues result improvements capability ability impart insight space aid pharmaceutical development.

Language: Английский

Citations

6