Homology modelling and molecular docking of MDR1 with chemotherapeutic agents in non-small cell lung cancer

Subhani, Syed; Jayaraman, Archana; Jamil, Kaiser

doi:10.1016/j.biopha.2015.02.009

Cited by 54 publications

(33 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…MDR1 also named ABCB1, it encodes P-glycoprotein which is an ATP-dependent drug efflux. It is responsible for decreased drug accumulation and often mediates the development of resistance to anticancer drug [61–63]. We found that both MDR1 C3435T and G2677T/A were associated with cisplatin-based chemotherapy response from the results of meta-analysis.…”

Section: Discussionmentioning

confidence: 92%

Pharmacogenomics of platinum-based chemotherapy response in NSCLC: a genotyping study and a pooled analysis

et al. 2016

View full text Add to dashboard Cite

Published data showed inconsistent results about associations of extensively studied polymorphisms with platinum-based chemotherapy response. Our study aimed to provide reliable conclusions of these associations by detecting genotypes of the SNPs in a larger sample size and summarizing a comprehensive pooled analysis. 13 SNPs in 8 genes were genotyped in 1024 NSCLC patients by SequenomMassARRAY. 39 published studies and our study were included in meta-analysis. Patients with GA or GG genotypes of XRCC1 G1196 had better response than AA genotype carriers (Genotyping study: OR = 0.72, 95%CI: 0.53-0.96, P = 0.028; Meta-analysis: OR = 0.74, 95%CI: 0.62-0.89, P = 0.001). Patients carrying CT or TT genotypes of XRCC1 C580T could be more sensitive to platinum-based chemotherapy compared to patients with CC genotype (OR = 0.54, 95%CI: 0.37-0.80, P = 0.002). CC genotype of XRCC3 C18067T carriers showed more resistance to platinum-based chemotherapy when compared to those with CT or TT genotypes (OR = 0.69, 95%CI: 0.52-0.91, P = 0.009). Our study indicated that XRCC1 G1196A/C580T and XRCC3 C18067T should be paid attention for personalized platinum-based chemotherapy in NSCLC patients.

show abstract

Section: Discussionmentioning

confidence: 92%

Pharmacogenomics of platinum-based chemotherapy response in NSCLC: a genotyping study and a pooled analysis

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Several groups have reported to negating, important molecular targets down the line of MDR pathway. In one report, through homology modeling and molecular docking, several chemotherapeutic inhibitors were screened against MDR1 or ABCB1 and it was found that the drug paclitaxel can be used for repurposing against MDR in non-small cell lung cancer [31]. Pharmacogenomics and molecular docking studies have shown that apigenin can inhibit ABC transporters such as Pglycoprotein and BRCP [32].…”

Section: Discussionmentioning

confidence: 99%

Molecular modeling and docking of small molecule inhibitors against NEK2

2016

View full text Add to dashboard Cite

Aberrant expression of NEK2 (NIMA-related kinase 2) is indicated in a wide variety of human cancers. NEK2 is highly correlated to multi drug resistance by activating drug efflux activity. Identification of new small molecule inhibitors targeted against NEK2 therefore, facilitates to increase drug sensitivity of cancer cells, by stabilizing drug influx and minimizes the dose of therapeutic drug. Our work investigates to screen for optimal small molecule inhibitors against NEK2. In this study, we used a computational approach by modeling NEK2 protein using I-TASSER (Iterative Threading ASSEmbly Refinement) software. The modeled structure was subjected to protein preparation wizard; to add hydrogens and to optimize the protonation states of His, Gln and Asn residues. Active site of the modeled protein was identified using SiteMap tool of Schrodinger package. We further carried out docking studies by means of Glide, with various ligands downloaded from EDULISS database. Based on glide score, potential ligands were screened and their interaction with NEK2 was identified. The best hits were further screened for Lipinski’s rule for drug-likeliness, bioactivity scoring and ADME properties. Thus, we report two (didemethylchlorpromazine and 2-[5-fluoro-1Hindol- 3-yl] propan-1-amine) compounds that have successfully satisfied all in silico parameters, necessitating further in vitro and in vivo studies.

show abstract

“…The obtained conformations of ligands during the docking are scored in Glide Standard Precision [40][41][42]. For each ligand, a maximum of 100 poses were requested throughout the docking [43,44].…”

Section: Protein-ligand Docking Simulationsmentioning

confidence: 99%

Combined ligand and structure-based virtual screening approaches for identification of novel AChE inhibitors

Şahin

Durdağı

2020

Turk J Chem

View full text Add to dashboard Cite

The excessive activity of acetylcholinesterase enzyme (AChE) causes different neuronal problems, especially dementia and neuronal cell deaths. Food and Drug Administration (FDA) approved drugs donepezil, rivastigmine, tacrine and galantamine are AChE inhibitors and in the treatment of Alzheimer’s disease (AD) these drugs are currently prescribed. However, these inhibitors have various adverse side effects. Therefore, there is a great need for the novel selective AChE inhibitors with fewer adverse side effects for the effective treatment. In this study, combined ligand-based and structure-based virtual screening approaches were used to identify new hit compounds from small molecules library of National Cancer Institute (NCI) containing approximately 265,000 small molecules. In the present study, we developed a computational pipeline method to predict the binding affinities of the studied compounds at the specific target sites. For this purpose, a text mining study was carried out initially and compounds containing the keyword “indol” were considered. The therapeutic activity values against AD were screened using the binary quantitative structure activity relationship (QSAR) models. We then performed docking, molecular dynamics (MD) simulations and free energy analysis to clarify the interactions between selected ligands and enzyme. Thus, in this study we identified new promising hit compounds from a large database that may be used to inhibit the enzyme activity of AChE.

show abstract

Homology modelling and molecular docking of MDR1 with chemotherapeutic agents in non-small cell lung cancer

Cited by 54 publications

References 42 publications

Pharmacogenomics of platinum-based chemotherapy response in NSCLC: a genotyping study and a pooled analysis

Pharmacogenomics of platinum-based chemotherapy response in NSCLC: a genotyping study and a pooled analysis

Molecular modeling and docking of small molecule inhibitors against NEK2

Combined ligand and structure-based virtual screening approaches for identification of novel AChE inhibitors

Contact Info

Product

Resources

About