In Silicon Approach for Discovery of Chemopreventive Agents

Increasing insight into the area of molecular cancer biology and structural biology has resulted in the disclosure of an increasing number of chemopreventive targets, which can be exploited for rapid rational discovery of chemopreventive agents. In this article, we discuss the application of in silicon approaches including molecular docking, pharmacophore modeling, fragment-based drug design, homology modeling, and target prediction in facilitating the search and designing of chemopreventive agents. These computational strategies have shown promising potential in speeding drug discovery and is expected to contribute to intelligent chemopreventive agents.

[1]  Paolo Vicini,et al.  Discovery of N-((3R,4R)-4-Fluoro-1-(6-((3-methoxy-1-methyl-1H-pyrazol-4-yl)amino)-9-methyl-9H-purin-2-yl)pyrrolidine-3-yl)acrylamide (PF-06747775) through Structure-Based Drug Design: A High Affinity Irreversible Inhibitor Targeting Oncogenic EGFR Mutants with Selectivity over Wild-Type EGFR. , 2017, Journal of medicinal chemistry.

[2]  Li M Fu.  Machine learning and tubercular drug target recognition. , 2014, Current pharmaceutical design.

[3]  Mike Wood,et al.  Application of Off-Rate Screening in the Identification of Novel Pan-Isoform Inhibitors of Pyruvate Dehydrogenase Kinase. , 2017, Journal of medicinal chemistry.

[4]  J. Sebolt-Leopold,et al.  Targeting MEK is effective chemoprevention of hepatocellular carcinoma in TGF-alpha-transgenic mice. , 2008, Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract.

[5]  Pagona Lagiou,et al.  Chemoprevention of cancer: current evidence and future prospects , 2015, F1000Research.

[6]  Rajesh Agarwal,et al.  Silibinin Treatment Inhibits the Growth of Hedgehog Inhibitor‐Resistant Basal Cell Carcinoma Cells via Targeting EGFR‐MAPK‐Akt and Hedgehog Signaling , 2017, Photochemistry and photobiology.

[7]  Brion W. Murray,et al.  Molecular conformations, interactions, and properties associated with drug efficiency and clinical performance among VEGFR TK inhibitors , 2012, Proceedings of the National Academy of Sciences.

[8]  Serena Dotolo,et al.  A theoretical study on predicted protein targets of apple polyphenols and possible mechanisms of chemoprevention in colorectal cancer , 2016, Scientific reports.

[9]  Xin Yu,et al.  Grifolin, a potent antitumour natural product upregulates death-associated protein kinase 1 DAPK1 via p53 in nasopharyngeal carcinoma cells. , 2011, European journal of cancer.

[10]  J. Mccammon,et al.  G-protein coupled receptors: advances in simulation and drug discovery. , 2016, Current opinion in structural biology.

[11]  Karel Berka,et al.  PDBsum additions , 2013, Nucleic Acids Res..

[12]  K. Brown,et al.  Cancer chemoprevention: a rapidly evolving field , 2013, British Journal of Cancer.

[13]  Jeffrey J. Gray,et al.  Computational modeling of membrane proteins , 2015, Proteins.

[14]  Zigang Dong,et al.  Neoalbaconol induces energy depletion and multiple cell death in cancer cells by targeting PDK1-PI3-K/Akt signaling pathway , 2013, Cell Death and Disease.

[15]  Bin Liu,et al.  Aspirin Inhibits IKK-β-mediated Prostate Cancer Cell Invasion by Targeting Matrix Metalloproteinase-9 and Urokinase-Type Plasminogen Activator , 2017, Cellular Physiology and Biochemistry.

[16]  Ping Pei,et al.  Reduced nonprotein thiols inhibit activation and function of MMP-9: implications for chemoprevention. , 2006, Free radical biology & medicine.

[17]  Neal K. Broomhead,et al.  Can We Rely on Computational Predictions To Correctly Identify Ligand Binding Sites on Novel Protein Drug Targets? Assessment of Binding Site Prediction Methods and a Protocol for Validation of Predicted Binding Sites , 2016, Cell Biochemistry and Biophysics.

[18]  Ruben Abagyan,et al.  Crystal structure of the chemokine receptor CXCR4 in complex with a viral chemokine , 2015, Science.

[19]  Eric T Baldwin,et al.  Developing Adnectins that target SRC co-activator binding to PXR: a structural approach toward understanding promiscuity of PXR. , 2015, Journal of molecular biology.

[20]  George D Geromichalos,et al.  Overview on the current status of virtual high-throughput screening and combinatorial chemistry approaches in multi-target anticancer drug discovery; Part I. , 2016, Journal of B.U.ON. : official journal of the Balkan Union of Oncology.

[21]  Savita Mishra,et al.  Synergistic Combination for Chemoprevention of Hepatocellular Carcinoma: An In Silico and In Vitro Approach , 2017, Basic & clinical pharmacology & toxicology.

[22]  A. Palumbo,et al.  Pharmacophore modeling technique applied for the discovery of proteasome inhibitors , 2014, Expert opinion on drug discovery.

[23]  Harren Jhoti,et al.  Twenty years on: the impact of fragments on drug discovery , 2016, Nature Reviews Drug Discovery.

[24]  H. Willems,et al.  Monoacidic Inhibitors of the Kelch-like ECH-Associated Protein 1: Nuclear Factor Erythroid 2-Related Factor 2 (KEAP1:NRF2) Protein-Protein Interaction with High Cell Potency Identified by Fragment-Based Discovery. , 2016, Journal of medicinal chemistry.

[25]  J. Sebolt-Leopold,et al.  Targeting MEK is Effective Chemoprevention of Hepatocellular Carcinoma in TGF-α-Transgenic Mice , 2007, Journal of Gastrointestinal Surgery.

[26]  Christopher K. Surratt,et al.  A Role for Fragment-Based Drug Design in Developing Novel Lead Compounds for Central Nervous System Targets , 2015, Front. Neurol..

[27]  Mineyuki Mizuguchi,et al.  Structural Insight into the Interactions between Death-Associated Protein Kinase 1 and Natural Flavonoids. , 2015, Journal of medicinal chemistry.

[28]  Y. Kao,et al.  Green tea (-)-epigallocatechin gallate inhibits the growth of human villous trophoblasts via the ERK, p38, AMP-activated protein kinase, and protein kinase B pathways. , 2016, American journal of physiology. Cell physiology.

[29]  Sam Kacew,et al.  Genetic and epigenetic cancer chemoprevention on molecular targets during multistage carcinogenesis , 2016, Archives of Toxicology.

[30]  Jane R. Allison.  Using simulation to interpret experimental data in terms of protein conformational ensembles. , 2017, Current opinion in structural biology.

[31]  Rafał Kurczab,et al.  The evaluation of QM/MM-driven molecular docking combined with MM/GBSA calculations as a halogen-bond scoring strategy. , 2017, Acta crystallographica Section B, Structural science, crystal engineering and materials.

[32]  Polina Mamoshina,et al.  Design of efficient computational workflows for in silico drug repurposing. , 2017, Drug discovery today.

[33]  Yuji Hatanaka,et al.  Evaluation of in vivo responses of sorafenib therapy in a preclinical mouse model of PTEN-deficient of prostate cancer , 2015, Journal of Translational Medicine.

[34]  Liming Lu,et al.  Aspirin as a potential modality for the chemoprevention of breast cancer: A dose-response meta-analysis of cohort studies from 857,831 participants , 2017, Oncotarget.

[35]  A. Jemal,et al.  Cancer statistics, 2014 , 2014, CA: a cancer journal for clinicians.

[36]  George D Geromichalos,et al.  Overview on the current status on virtual high-throughput screening and combinatorial chemistry approaches in multi-target anticancer drug discovery; Part II. , 2016, Journal of B.U.ON. : official journal of the Balkan Union of Oncology.

[37]  Ronen Marmorstein,et al.  Chemically Linked Vemurafenib Inhibitors Promote an Inactive BRAFV600E Conformation. , 2016, ACS chemical biology.

[38]  Armando Rossello,et al.  N-O-Isopropyl Sulfonamido-Based Hydroxamates as Matrix Metalloproteinase Inhibitors: Hit Selection and in Vivo Antiangiogenic Activity. , 2015, Journal of medicinal chemistry.

[39]  Dolores Diaz,et al.  Discovery of (S)-1-(1-(4-Chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (GDC-0994), an Extracellular Signal-Regulated Kinase 1/2 (ERK1/2) Inhibitor in Early Clinical Development. , 2016, Journal of medicinal chemistry.

[40]  Thuluz Meza-Menchaca,et al.  In Silico Analysis of Lanostanoids Characterized in Ganoderma Mushrooms (Agaricomycetes) as Potential Ligands of the Vitamin D Receptor. , 2016, International journal of medicinal mushrooms.

[41]  Young Jun Kim,et al.  Structure-Based Virtual Screening of Protein Tyrosine Phosphatase Inhibitors: Significance, Challenges, and Solutions. , 2017, Journal of microbiology and biotechnology.

[42]  Liang Liang,et al.  Inhibitory effect of silibinin on EGFR signal-induced renal cell carcinoma progression via suppression of the EGFR/MMP-9 signaling pathway. , 2012, Oncology reports.

[43]  Lee Jia,et al.  Abortifacient metapristone (RU486 derivative) interrupts CXCL12/CXCR4 axis for ovarian metastatic chemoprevention , 2017, Molecular carcinogenesis.

[44]  Wei Li,et al.  Grifolin directly targets ERK1/2 to epigenetically suppress cancer cell metastasis , 2015, Oncotarget.

[45]  Wei Zhang,et al.  Inhibitory effect of oleanolic acid on hepatocellular carcinoma via ERK-p53-mediated cell cycle arrest and mitochondrial-dependent apoptosis. , 2013, Carcinogenesis.

[46]  Marc Bissonnette,et al.  Colon cancer and the epidermal growth factor receptor: Current treatment paradigms, the importance of diet, and the role of chemoprevention. , 2015, World journal of clinical oncology.

[47]  Rahul Parikh,et al.  CXCR4 Is a Novel Target of Cancer Chemopreventative Isothiocyanates in Prostate Cancer Cells , 2015, Cancer Prevention Research.

[48]  Meng-Chen Lu,et al.  The Keap1–Nrf2–ARE Pathway As a Potential Preventive and Therapeutic Target: An Update , 2016, Medicinal research reviews.

[49]  Stefan Laufer,et al.  Optimized Target Residence Time: Type I1/2 Inhibitors for p38α MAP Kinase with Improved Binding Kinetics through Direct Interaction with the R-Spine. , 2017, Angewandte Chemie.

[50]  Yoshinori Matsuura,et al.  Multiple binding modes of a small molecule to human Keap1 revealed by X-ray crystallography and molecular dynamics simulation , 2015, FEBS open bio.

[51]  David S. Goodsell,et al.  The RCSB protein data bank: integrative view of protein, gene and 3D structural information , 2016, Nucleic Acids Res..

[52]  C. Wermuth,et al.  Glossary of terms used in medicinal chemistry (IUPAC Recommendations 1998) , 1998 .

[53]  John H. White,et al.  Synthetically accessible non-secosteroidal hybrid molecules combining vitamin D receptor agonism and histone deacetylase inhibition. , 2012, Chemistry & biology.

[54]  Michelle L Coote,et al.  Molecular dynamics-driven drug discovery: leaping forward with confidence. , 2017, Drug discovery today.

[55]  Ling Tian,et al.  Aspirin in pancreatic cancer: chemopreventive effects and therapeutic potentials. , 2016, Biochimica et biophysica acta.

[56]  C. Fishwick,et al.  New Opportunities in the Structure-based Design of Anti-Protozoan Agents. , 2016, Current topics in medicinal chemistry.

[57]  A. Odermatt,et al.  Pharmacophore Models and Pharmacophore-Based Virtual Screening: Concepts and Applications Exemplified on Hydroxysteroid Dehydrogenases , 2015, Molecules.

[58]  Edward Messing,et al.  A positive feedback signaling loop between ATM and the vitamin D receptor is critical for cancer chemoprevention by vitamin D. , 2012, Cancer research.

[59]  Dariusz Matosiuk,et al.  Recent Advances and Applications of Molecular Docking to G Protein-Coupled Receptors , 2017, Molecules.

[60]  Bruce Blumberg,et al.  Activation of the steroid and xenobiotic receptor, SXR, induces apoptosis in breast cancer cells , 2009, BMC Cancer.

[61]  G. Wolber,et al.  More than a look into a crystal ball: protein structure elucidation guided by molecular dynamics simulations. , 2016, Drug discovery today.