Multiclass Comparative Virtual Screening to Identify Novel Hsp90 Inhibitors: A Therapeutic Breast Cancer Drug Target

Dunna, Nageswara Rao; Akare, Uday Raj; Rajadhyax, Siddheshwar; Gutlapalli, Venkata Ravi; Yadav, Mukesh; Nayarisseri, Anuraj

doi:10.2174/1568026615666150112113627

Cited by 29 publications

(14 citation statements)

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“…The dual inhibitor DHP1808 with a novel structure is shown in Figure 1A. Its half maximal inhibitory concentrations against Hsp90 and PI3Kα were at sub-micromolar levels, as reported in our recent reports [21,[35][36][37][38][39]. No obvious off-target kinase inhibition was observed (Table S1).…”

Section: Novel Hsp90/pi3ka Dual Inhibitor Dhp1808 Suppresses A375 Celsupporting

confidence: 68%

Novel HSP90-PI3K Dual Inhibitor Suppresses Melanoma Cell Proliferation by Interfering with HSP90-EGFR Interaction and Downstream Signaling Pathways

Zhao

Zhu

Xie

et al. 2020

IJMS

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Melanoma is the deadliest form of skin cancer, and its incidence has continuously increased over the past 20 years. Therefore, the discovery of a novel targeted therapeutic strategy for melanoma is urgently needed. In our study, MTT-based cell proliferation assay, cell cycle, and apoptosis assays through flow cytometry, protein immunoblotting, protein immunoprecipitation, designing of melanoma xenograft models, and immunohistochemical/immunofluorescent assays were carried out to determine the detailed molecular mechanisms of a novel HSP90-PI3K dual inhibitor. Our compound, named DHP1808, was found to suppress A375 cell proliferation through apoptosis induction by activating the Fas/FasL signaling pathway; it also induced cell-cycle arrest and inhibited the cell migration and invasion of A375 cells by interfering with Hsp90-EGFR interactions and downstream signaling pathways. Our results indicate that DHP1808 could be a promising lead compound for the Hsp90/PI3K dual inhibitor.

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Section: Novel Hsp90/pi3ka Dual Inhibitor Dhp1808 Suppresses A375 Celsupporting

confidence: 68%

Novel HSP90-PI3K Dual Inhibitor Suppresses Melanoma Cell Proliferation by Interfering with HSP90-EGFR Interaction and Downstream Signaling Pathways

Zhao

Zhu

Xie

et al. 2020

IJMS

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“…Furthermore, the complete hoard of inhibitors in the form of of 3D structures was prepared using OPLS 2005 force field algorithm embedded in the LegPrep module of Schrödinger suite, 2013 (Schrodinger. LLC, New York, NY) (Babitha et al, 2015;Bandaru et al, 2017a;Basak et al, 2016a, Dunna et al, 2015a. Eventually, in this procedure of preparation, the protein was added with disulfide bonds, missing side chains were filled, water molecules were removed beyond 5 Å from hetero groups, and was saved in the SDF format for further docking studies (Dunna et al, 2015b;Divya et al, 2019;Bandaru et al, 2015a;Kelotra et al, 2014a;Basak et al, 2016b).…”

Section: Protein and Ligand Preparationmentioning

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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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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“…Among the compounds with the highest docking rerank scores, a new candidate (Pubchem CID: 11363378) that demonstrated considerable affinity towards Hsp90 was identified. Their study can serve as a model for searching for anticancer drugs based on the protein-ligand interaction [ 31 ].…”

Section: Cmda Of Catechin-protein Interactionmentioning

confidence: 99%

Computational Molecular Docking and X-ray Crystallographic Studies of Catechins in New Drug Design Strategies

et al. 2018

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Epidemiological and laboratory studies have shown that green tea and green tea catechins exert beneficial effects on a variety of diseases, including cancer, metabolic syndrome, infectious diseases, and neurodegenerative diseases. In most cases, (−)-epigallocatechin gallate (EGCG) has been shown to play a central role in these effects by green tea. Catechins from other plant sources have also shown health benefits. Many studies have revealed that the binding of EGCG and other catechins to proteins is involved in its action mechanism. Computational docking analysis (CMDA) and X-ray crystallographic analysis (XCA) have provided detailed information on catechin-protein interactions. Several of these studies have revealed that the galloyl moiety anchors it to the cleft of proteins through interactions with its hydroxyl groups, explaining the higher activity of galloylated catechins such as EGCG and epicatechin gallate than non-galloylated catechins. In this paper, we review the results of CMDA and XCA of EGCG and other plant catechins to understand catechin-protein interactions with the expectation of developing new drugs with health-promoting properties.

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Multiclass Comparative Virtual Screening to Identify Novel Hsp90 Inhibitors: A Therapeutic Breast Cancer Drug Target

Cited by 29 publications

References 0 publications

Novel HSP90-PI3K Dual Inhibitor Suppresses Melanoma Cell Proliferation by Interfering with HSP90-EGFR Interaction and Downstream Signaling Pathways

Novel HSP90-PI3K Dual Inhibitor Suppresses Melanoma Cell Proliferation by Interfering with HSP90-EGFR Interaction and Downstream Signaling Pathways

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

Computational Molecular Docking and X-ray Crystallographic Studies of Catechins in New Drug Design Strategies

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