Current Pharmaceutical Design - Volume 31, Issue 9, 2025
Volume 31, Issue 9, 2025
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PARP Pioneers: Using BRCA1/2 Mutation-targeted Inhibition to Revolutionize Breast Cancer Treatment
Authors: Navneet Sharma, Akash Bhati, Shagun Aggarwal, Kamal Shah and Hitesh Kumar DewanganBreast cancer stands on the second position in the world in being common and women happen to have it with high rate of about five-folds around the world. The causes of occurrence can matter with different humans be it external factors or the internal genetic ones. Breast cancer is primarily driven by mutations in the BRCA1 and BRCA2 susceptibility genes. These BC susceptibility genes encode proteins critical for DNA homologous recombination repair (HRR). Poly (ADP ribose) polymerases (PARP) are the essential enzymes involved in the repairing of the damaged DNA. So the inhibition of these inhibitors can be considered as the promising strategy for targeting cancers with defective damage in the deoxyribonucleic acid. Olaparib and talazoparib are PARP inhibitors (PARPi) are being employed for the monotherapies in case of the deleterious germline HER2-negative and BRCA-mutated breast cancer. The potency of PARP for trapping on DNA and causes cytotoxicity may have difference in the safety and efficacy with the PARPi. The PARPi have been found its place in the all different types of breast cancers and have shown potential benefits. The purpose of this review is to provide an update on the oral poly (ADP-ribose) polymerase (PARP) inhibitors for the improvement in the treatment and management of breast cancer.
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Circulating Tumor Cells in Cancer Diagnosis, Therapy, and Theranostics Applications: An Overview of Emerging Materials and Technologies
Authors: Sina Soleymani, Seyed Morteza Naghib and M.R. MozafariIn recent years, immunotherapy, namely immune checkpoint inhibitor therapy, has significantly transformed the approach to treating various forms of cancer. Simultaneously, the adoption of clinical oncology has been sluggish due to the exorbitant expense of therapy, the adverse effects experienced by patients, and the inconsistency in treatment response among individuals. As a reaction, individualized methods utilizing predictive biomarkers have arisen as novel strategies for categorizing patients to achieve successful immunotherapy. Recently, the identification and examination of circulating tumor cells (CTCs) have gained attention as predictive indicators for the treatment of cancer patients undergoing chemotherapy and for personalized targeted therapy. CTCs have been found to exhibit immunological checkpoints in several types of solid tumors, which has contributed to our understanding of managing cancer immunotherapy. Circulating tumor cells (CTCs) present in the bloodstream have a crucial function in the formation of metastases. Nevertheless, the practical usefulness of existing CTC tests is mostly restricted by methodological limitations.
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Chitosan-grafted Graphene Materials for Drug Delivery in Wound Healing
More LessThe effective and prompt treatment of wounds remains a significant challenge in clinical settings. Consequently, recent investigations have led to the development of a novel wound dressing production designed to expedite the process of wound healing with minimal adverse complications. Chitosan, identified as a natural biopolymer, emerges as an appealing option for fabricating environmentally friendly dressings due to its biologically degradable, nonpoisonous, and inherent antimicrobial properties. Concurrently, graphene oxide has garnered attention from researchers as an economical, biocompatible material with non-toxic attributes for applications in wound healing. Chitosan (CS) has been extensively studied in agglutination owing to its advantageous properties, such as Non-toxicity biological compatibility, degradability, and facilitation of collagen precipitation. Nonetheless, its limited Medium mechanical and antibacterial strength characteristics impede its widespread clinical application. In addressing these shortcomings, numerous researchers have embraced nanotechnology, specifically incorporating metal nanoparticles (MNPs), to enhance the mechanical power and targeted germicide features of chitosan multistructures, yielding hopeful outcomes. Additionally, chitosan is a decreasing factor for MNPs, contributing to reduced cytotoxicity. Consequently, the combination of CS with MNPs manifests antibacterial function, superior mechanical power, and anti-inflammatory features, holding significant potential to expedite wound healing. This study delves into based on chitosan graphene materials in the context of wound healing.
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Establishment of an Integrated Population Pharmacokinetic/ Pharmacodynamics Model of Apixaban in Chinese Healthy Population Adjusting for Key Genetic Variants
Authors: Guangyan Mu, Yaou Liu, Qiufen Xie, Zhiyan Liu, Hanxu Zhang, Xianmin Meng, Jinfang Song, Zhe Wang, Shuang Zhou, Zining Wang, Kun Hu, Xia Zhao, Maoxing Liao, Jiachun Bao, Qian Xiang and Yimin CuiAimsTo improve the understanding of pharmacokinetic/pharmacodynamic (PK/PD) profiles of apixaban, supporting personalised drug prescriptions for future patients.
BackgroundGenetic as well as nongenetic factors can affect the predictable PK and PD characteristics of apixaban.
ObjectiveEstablish a integrated popPK/PD model that adjusts for critical genetic variant.
MethodsThe integrated PK/PD models was characterized on the basis of PK (apixaban blood concentration) and PD (prothrombin time (PT), activated partial thromboplastin time (APTT), and anti-FXa activity) data from 181 healthy Chinese volunteers. Other investigated covariate variables included: Meaningful intrinsic and extraneous determinants, correlated genetic factors (ABCG2, F13A1, C3, etc.). A total of 2877 PK concentration observations were included in the modeling dataset.
ResultsThe PK model of apixaban is adopted by single compartment model with first-order oral absorption. The estimated values of total clearance rate (CL/F), apparent distribution volume (V/F), and absorption rate constant (KA) in the final model are 3.37 L/h, 28.2 L, and 0.781 1/h, respectively. The PK model includes significance covariates such as FOOD, RBC, WT, and gene (ABCG2). The PD model of apixaban is adopted by a linear direct effect model with additive error, which was used to describe the relationship between markers such as APTT, PT, anti-FXa, versus plasma concentration. PK simulation within the modelled dose range is similar to clinical real date, while PD simulation results also show that the simulated exposure parameters is within the range of the literature.
ConclusionWe established a comprehensive PK/PD model and used it to simulate markers level such as APTT, PT, and anti-FXa of apixaban. Individual predictive values with a dose of 2.5 mg are basically within the expected recommended range.
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Network Pharmacological Analysis of Hydroxychloroquine Intervention in the Treatment of Iga Nephropathy
Authors: Mengxiao Zou, Gang Xu, Shuwang Ge, Kanglin Guo, Qian Duo and Yichun ChengBackgroundIgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis globally and has a high propensity to develop into end-stage renal disease (ESRD). Hydroxychloroquine has been proven to reduce proteinuria in IgAN patients, but the precise mechanism remains unclear. Therefore, network pharmacology was used to investigate the mechanism.
MethodsPubChem and SwissADME databases were utilized to acquire the structure of hydroxychloroquine. The SwissTargetPrediction, PharmMapper, DrugBank, TargetNet, and BATMAN-TCM databases were then utilized to obtain the targets. The target genes related to IgAN were then gathered from the databases, which included GeneCards, PHARMGKB, DrugBank, OMIM, and DisGeNET. Common targets were obtained by UniProt. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to define the main molecular mechanisms and pathways. Furthermore, a protein-protein interaction (PPI) network was constructed using the STRING tool, and the core targets were obtained by Cytoscape. Finally, molecular docking between the core targets and hydroxychloroquine was performed.
Results167 common target genes were acquired by overlapping. The core targets were TNF, ALB, IL1B, JUN, FOS, SRC, and MMP9. The GO and KEGG results showed the targets to be related to the production of inflammatory cytokines and chemokines and were engaged in the toll-like receptor (TLR) signaling pathway. At the same time, the molecular docking results showed that the core targets all combined with hydroxychloroquine closely.
ConclusionThis study proved that hydroxychloroquine may treat IgAN through the TLR signaling pathway, and the restraint of TNF, TLR, IL1B, and JUN may be essential for the treatment.
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Volumes & issues
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Volume 31 (2025)
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Volume 30 (2024)
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Volume 29 (2023)
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Volume 28 (2022)
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Volume 27 (2021)
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Volume 26 (2020)
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Volume 25 (2019)
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Volume 24 (2018)
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Volume 23 (2017)
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Volume 22 (2016)
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Volume 21 (2015)
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Volume 20 (2014)
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Volume 19 (2013)
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Volume 18 (2012)
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Volume 17 (2011)
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Volume 16 (2010)
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Volume 15 (2009)
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Volume 14 (2008)
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Volume 13 (2007)
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Volume 12 (2006)
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Volume 11 (2005)
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Volume 10 (2004)
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Volume 9 (2003)
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Volume 8 (2002)
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Volume 7 (2001)
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Volume 6 (2000)
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