An Alignment-Independent 3D-QSAR Study of FGFR2 Tyrosine Kinase Inhibitors

Jafari, Behzad; Hamzeh‐Mivehroud, Maryam; Alizadeh, Ali; Sharifi, Mehdi; Dastmalchi, Siavoush

doi:10.15171/apb.2017.049

Cited by 4 publications

(1 citation statement)

References 28 publications

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“…Fibroblast Growth Factor Receptor (FGFR)-Mediated Nanoparticles. FGFR, a transmembrane tyrosine kinase receptor located on the surface of TAFs, 113 consists of cell surface receptors of four structural subtypes (FGFR1−4) that bind to fibroblast growth factor (FGFs) and play an important role in many biological processes. 114 FGFR expression is highly specific to tumor stromal cells but lacks expression in tumor and other nontumor cells.…”

Section: Molecularmentioning

confidence: 99%

Tumor-Associated Fibroblast-Targeting Nanoparticles for Enhancing Solid Tumor Therapy: Progress and Challenges

Little

Park

et al. 2021

Mol. Pharmaceutics

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Even though nanoparticle drug delivery systems (nanoDDSs) have improved antitumor efficacy by delivering more drugs to tumor sites compared to free and unencapsulated therapeutics, achieving satisfactory distribution and penetration of nanoDDSs inside solid tumors, especially in stromal fibrous tumors, remains challenging. As one of the most common stromal cells in solid tumors, tumor-associated fibroblasts (TAFs) not only promote tumor growth and metastasis but also reduce the drug delivery efficiency of nanoparticles through the tumor’s inherent physical and physiological barriers. Thus, TAFs have been emerging as attractive targets, and TAF-targeting nanotherapeutics have been extensively explored to enhance the tumor delivery efficiency and efficacy of various anticancer agents. The purpose of this Review is to opportunely summarize the underlying mechanisms of TAFs on obstructing nanoparticle-mediated drug delivery into tumors and discuss the current advances of a plethora of nanotherapeutic approaches for effectively targeting TAFs.

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Section: Molecularmentioning

confidence: 99%

Tumor-Associated Fibroblast-Targeting Nanoparticles for Enhancing Solid Tumor Therapy: Progress and Challenges

Little

Park

et al. 2021

Mol. Pharmaceutics

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Alignment independent 3D-QSAR studies and molecular dynamics simulations for the identification of potent and selective S1P1 receptor agonists

Alizadeh

Jafari

Dastmalchi

2020

Journal of Molecular Graphics and Modelling

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a b s t r a c tSphingosine 1-phosphate type 1 (S1P 1 ) receptors are expressed on lymphocytes and regulate immune cells trafficking. Sphingosine 1-phosphate and its analogues cause internalization and degradation of S1P 1 receptors, preventing the auto reactivity of immune cells in the target tissues. It has been shown that S1P 1 receptor agonists such as fingolimod can be suitable candidates for treatment of autoimmune diseases. The current study aimed to generate GRIND-based 3D-QSAR predictive models for agonistic activities of 2-imino-thiazolidin-4-one derivatives on S1P 1 to be used in virtual screening of chemical libraries. The developed model for the S1P 1 receptor agonists showed appropriate power of predictivity in internal (r 2 acc 0.93 and SDEC 0.18) and external (r 2 0.75 and MAE (95% data), 0.28) validations. The generated model revealed the importance of variables DRY-N1 and DRY-O in the potency and selectivity of these compounds towards S1P 1 receptor. To propose potential chemical entities with S1P 1 agonistic activity, PubChem chemicals database was searched and the selected compounds were virtually tested for S1P 1 receptor agonistic activity using the generated models, which resulted in four potential compounds with high potency and selectivity towards S1P 1 receptor. Moreover, the affinities of the identified compounds towards S1P 1 receptor were evaluated using molecular dynamics simulations. The results indicated that the binding energies of the compounds were in the range of À39.31 to À46.18 and À3.20 to À9.75 kcal mol À1 , calculated by MM-GBSA and MM-PBSA algorithms, respectively. The findings in the current work may be useful for the identification of potent and selective S1P 1 receptor agonists with potential use in diseases such as multiple sclerosis.

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Acidic tumor microenvironment-sensitive liposomes enhance colorectal cancer therapy by acting on both tumor cells and cancer-associated fibroblasts

Gong

et al. 2021

Nanoscale

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An Alignment-Independent 3D-QSAR Study of FGFR2 Tyrosine Kinase Inhibitors

Cited by 4 publications

References 28 publications

Tumor-Associated Fibroblast-Targeting Nanoparticles for Enhancing Solid Tumor Therapy: Progress and Challenges

Tumor-Associated Fibroblast-Targeting Nanoparticles for Enhancing Solid Tumor Therapy: Progress and Challenges

Alignment independent 3D-QSAR studies and molecular dynamics simulations for the identification of potent and selective S1P1 receptor agonists

Acidic tumor microenvironment-sensitive liposomes enhance colorectal cancer therapy by acting on both tumor cells and cancer-associated fibroblasts

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