An In silico Approach to Identify High Affinity Small Molecule Targeting m-TOR Inhibitors for the Clinical Treatment of Breast Cancer

Patidar, Khushboo; Panwar, Umesh; Vuree, Sugunakar; Sweta, Jajoriya; Sandhu, Manpreet Kaur; Nayarisseri, Anuraj

doi:10.31557/apjcp.2019.20.4.1229

Cited by 37 publications

(12 citation statements)

References 92 publications

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“…Similarity search was carried out to obtain the best compound having greater affinity other than any established drugs. The filtration properties parameter set by component rule of Lipinski's rule of five at Threshold >=95% against NCBI's Pubchem compound database which is a NIH organized public chemical repository of 93 million chemical compounds (Patidar et al, 2019;Monteiro et al, 2019;Rao et al, 2010;Shaheen et al, 2015). As a result, the complete compounds retrieved were again compared with docking studies to obtain a candidate with a better affinity that can halt target protein IDH2.…”

Section: Structure-based Virtual Screeningmentioning

confidence: 99%

“…The BOILED-Egg plot of 4 candidates having two favorable properties: Blood brain barrier and gastrointestinal absorption bestow an efficient pharmacokinetics profile (Padmini et al, 2019;Sinha et al, 2019;Palak et al, 2019;Patidar et al, 2019;Khandelwal et al, 2018;Majhi et al, 2018). Two compounds were selected from established docked results: Enasidenib mesylate (PubChem ID-89683805) and AG-120(PubChem CID-89699486).…”

Section: Boiled Egg Plot Analysismentioning

confidence: 99%

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Identification of High-Affinity Small Molecule Targeting IDH2 for the Clinical Treatment of Acute Myeloid Leukemia

Sweta¹,

Khandelwal²,

Srinitha³

et al. 2019

Asian Pac J Cancer Prev

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According to the American Cancer Society (ACS), Acute Myeloid Leukemia (AML) is a group of hematological diseases, phenotypic and genetically heterogeneous, characterized by clonal expansion of myeloid with diminished capacity for differentiation. It is characterized by the fast growth of white blood cells, red blood cells, platelets, and it's a build-up in the bone marrow restricting the production of traditional blood cells. Once healthy bone marrow cells are replaced with the leukemic cells, it results in a decline in red blood cells, platelets, and healthy white blood cells. Mainly, symptoms that are seen in patients affected by AML are Weight loss, Fatigue, Fever, Night sweat, Loss of appetite, shortness of breath, natural bruising and bleeding, with lots of body

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Section: Structure-based Virtual Screeningmentioning

confidence: 99%

Section: Boiled Egg Plot Analysismentioning

confidence: 99%

Identification of High-Affinity Small Molecule Targeting IDH2 for the Clinical Treatment of Acute Myeloid Leukemia

Sweta¹,

Khandelwal²,

Srinitha³

et al. 2019

Asian Pac J Cancer Prev

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“…X-ray crystal structure of the ERα in complex with 4-hydroxytamoxifen (OHT)(PDB Id: 3ERT [29] was selected for the present study by considering Resolution (1.9 Å), and R-Value Free (0.262) as speci c selection parameters from the Protein Data Bank [30][31][32][33][34][35][36][37][38]. Before proceeding to dock, the PDB structure was prepared using the Protein Preparation Wizard module(Schrodinger, Inc., LLC, New York, USA) by applying criteria like removal of water molecules, assigning bond orders, lling missing hydrogens, side chains & loops, capping termini, selenomethionine to methionine reconversion, optimization and energy minimization using the OPLS-2005 force eld with default settings [39][40][41][42][43][44][45][46][47][48][49][50].…”

Section: Target Selection and Protein Preparationmentioning

confidence: 99%

Structural insights into conformational stability of ESR1 and structure base screening of new potent inhibitor for the treatment of Breast Cancer

Chopra¹,

Panwar

Madhavi

et al. 2022

Preprint

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Estrogen receptor alpha (ERα), a nuclear receptor proteinencoded by the estrogen receptor1 (ESR1) gene,is an important biomarker in breast cancer diagnosis. Any dysregulation in its expression can actively implicate the development and progression of the disease. ERα is abnormally expressed in around 60% of the active cases, making it animportant therapeutic target. In this study, we report the application of computational approaches to identify suitable drug-like molecules, which share similar ligand binding dynamics with ERα. Structure-based virtual screening(SBVS), docking, and inhibitor dynamics are used to study the ligand binding and interaction profiling of the anticipatedligand molecule, at the active site of the 4-hydroxytamoxifen (OHT) protein (PDB Id: 3ERT). SBVS analysis follows HTVS, SP, and XP protocol in comparison to the ZINC and NCI, to retrieve 20 bestligandhits as effective inhibitors; All the compounds have shown significant interaction with active site residues (Leu346, Thr347, Asp351, Glu353, Trp383, Leu387, and Arg394) of the 4-hydroxytamoxifen. Moreover, the docking study was used to screen the top 5 compounds: ZINC13377936, NCI35753, ZINC35465238, ZINC14726791, and NCI663569. We also, employed molecular dynamics simulations to explore the binding dynamics present at the atomic level. Our MDS results have revealed the compounds (ZINC13377936 and NCI35753) with outstanding binding stability and lesser fluctuations. Both above hits possess a high potential as future therapeutic agents, acting by the mechanism of competitive inhibitionagainst the ERα protein in breast cancer.

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“…INTRODUCTION: Docking-based drug design by using the structure of target protein remains one of the most rational and speedy approaches in drug discovery paradigms. The knowledge about the amino acid residues interacting with the specific groups of the chemical entity leads to proposals for the synthesis of the new highly potent chemical entities 1 . In recent years, virtual screening by computational methods has become an essential part of drug discovery projects 2 .…”

Section: Ijpsr (2021) Volume 12 Issue 3 (Research Article)mentioning

confidence: 99%

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An In silico Approach to Identify High Affinity Small Molecule Targeting m-TOR Inhibitors for the Clinical Treatment of Breast Cancer

Cited by 37 publications

References 92 publications

Identification of High-Affinity Small Molecule Targeting IDH2 for the Clinical Treatment of Acute Myeloid Leukemia

Identification of High-Affinity Small Molecule Targeting IDH2 for the Clinical Treatment of Acute Myeloid Leukemia

Structural insights into conformational stability of ESR1 and structure base screening of new potent inhibitor for the treatment of Breast Cancer

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