<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.2d1 20170631//EN" "JATS-journalpublishing1.dtd">
      <Volume-Issue>Volume 11, Issue 3</Volume-Issue>
      <Season>July - September, 2019</Season>
      <ArticleTitle>Molecular docking analysis of 5,6,7,8-tetrahydropyrido[3,4-d] pyrimidine derivatives as ERK2 inhibitors</ArticleTitle>
      <Abstract>ERK1 and ERK2 are one of the important targets, involved in various types of cancers such as breast, lung, prostate, and ovarian cancer. ERK1 and ERK2 belong to the mitogen-activated family, thus also known as mitogen-activated protein kinases (MAPKs) and both possess 85% similarity in their amino acid sequence. In silico techniques like molecular docking are continuously utilized in the identification of new molecules as lead for the development of bioactive compounds. Molecular docking predicts the binding orientation of small molecule drug candidates to their protein targets. In this study, we performed the molecular docking studies of small library of heterocycles against ERK2 (PDB ID: 2OJJ) using docking software MOE 2008.10. Binding energy score of each designed molecules was calculated and results were compared with standard ligand 82A. The results displayed that most of the compounds were occupied the same binding cavity of protein and also showed the similar interactions when compared to the standard ligand 82 A. Among all ligand 11 exhibits the highest binding energy score of ?11.6464 kcal/mol comparable to the 82A with binding energy score of ?9.2447kcal/ mol and showed interactions with residue Met-106.</Abstract>
      <Keywords>ERK2, In silico, Molecular docking analysis, MOE</Keywords>
        <Abstract>https://isfcppharmaspire.com/ubijournal-v1copy/journals/abstract.php?article_id=13856&amp;title=Molecular docking analysis of 5,6,7,8-tetrahydropyrido[3,4-d] pyrimidine derivatives as ERK2 inhibitors</Abstract>
        <References>1. Mirzoeva OK, Das D, Heiser LM, Bhattacharya S, Siwak D, Gendelman R, et al. Basal subtype and MAPK/ERK kinase (MEK)-phosphoinositide 3-kinase feedback signaling determine susceptibility of breast cancer cells to MEK inhibition. Cancer Res 2009;69:565-72. &#13;
2. Pathania S, Rawal RK. An update on chemical classes targeting ERK1/2 for the management of cancer. Future Med Chem 2020;12:593-11. &#13;
3. Santen RJ, Song RX, McPherson R, Kumar R, Adam L, Jeng MH, et al. The role of mitogen-activated protein (MAP) kinase in breast cancer. J Steroid Biochem Mol Biol 2002;80:239-56. &#13;
4. Huang N, Shoichet BK, Irwin JJ. Benchmarking sets for molecular docking. J Med Chem 2006;49:6789-801.&#13;
5. Morris GM, Lim-Wilby M. Molecular Docking. Berlin, Germany: Springer; 2008. p. 365-82. &#13;
6. Yee AA, Savchenko A, Ignachenko A, Lukin J, Xu X, Skarina T, et al. NMR and X-ray crystallography, complementary tools in structural proteomics of small proteins. J Am Chem Soc 2005;127:16512-7.&#13;
7. Asati V, Mahapatra DK, Bharti SK. PI3K/Akt/mTOR and Ras/Raf/MEK/ ERK signaling pathways inhibitors as anticancer agents: Structural and pharmacological perspectives. Eur J Med Chem 2016;109:314-41.&#13;
8. Amin KM, Syam YM, Anwar MM, Ali HI, Abdel-Ghani TM, Serry AM. Synthesis and molecular docking study of new benzofuran and furo [3, 2-g] chromone-based cytotoxic agents against breast cancer and p38and;alpha; MAP kinase inhibitors. Bioorg Chem 2018;76:487-500. &#13;
9. Yari H, Ganjalikhany MR, Sadegh H. In silico investigation of new binding pocket for mitogen activated kinase kinase (MEK): Development of new promising inhibitors. Comput Biol Chem 2015;59:185-98. &#13;
10. Kohno M, Pouyssegur J. Targeting the ERK signaling pathway in cancer therapy. Ann Med 2006;38:200-11. &#13;
11. Allen LF, Sebolt-Leopold J, Meyer MB. CI-1040 (PD184352), a targeted signal transduction inhibitor of MEK (MAPKK). Semin Oncol 2003;5 Suppl 16:105-16. &#13;
12. Yeh TC, Marsh V, Bernat BA, Ballard J, Colwell H, Evans RJ, et al. Biological characterization of ARRY-142886 (AZD6244), a potent, highly selective mitogen-activated protein kinase kinase 1/2 inhibitor. Clin Cancer Res 2007;13:1576-83. &#13;
13. Blake JF, Gaudino JJ, De Meese J, Mohr P, Chicarelli M, Tian H, et al. Discovery of 5, 6, 7, 8-tetrahydropyrido [3, 4-d] pyrimidine inhibitors of Erk2. Bioorg Med Chem Lett 2014;24:2635-9. &#13;
14. Chemical Computing Group. Molecular Operating Environment, 2008.10. Montreal: Chemical Computing Group; 2008.</References>