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International journal of molecular sciences
Sep 11, 2023;24 (18):

An Updated Review on Developing Small Molecule Kinase Inhibitors Using Computer-Aided Drug Design Approaches.

Linwei Li, Songtao Liu, Bi Wang, Fei Liu, Shu Xu, Pirui Li, Yu Chen
Author Information
  1. Linwei Li: Jiangsu Key Laboratory for the Research and Utilization of Plant Resources, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China. ORCID
  2. Songtao Liu: Jiangsu Key Laboratory for the Research and Utilization of Plant Resources, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China.
  3. Bi Wang: Jiangsu Key Laboratory for the Research and Utilization of Plant Resources, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China.
  4. Fei Liu: Jiangsu Key Laboratory for the Research and Utilization of Plant Resources, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China.
  5. Shu Xu: Jiangsu Key Laboratory for the Research and Utilization of Plant Resources, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China.
  6. Pirui Li: Jiangsu Key Laboratory for the Research and Utilization of Plant Resources, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China.
  7. Yu Chen: Jiangsu Key Laboratory for the Research and Utilization of Plant Resources, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China.
PMID: 37762253 DOI: 10.3390/ijms241813953

Abstract

Small molecule kinase inhibitors (SMKIs) are of heightened interest in the field of drug research and development. There are 79 (as of July 2023) small molecule kinase inhibitors that have been approved by the FDA and hundreds of kinase inhibitor candidates in clinical trials that have shed light on the treatment of some major diseases. As an important strategy in drug design, computer-aided drug design (CADD) plays an indispensable role in the discovery of SMKIs. CADD methods such as docking, molecular dynamic, quantum mechanics/molecular mechanics, pharmacophore, virtual screening, and quantitative structure-activity relationship have been applied to the design and optimization of small molecule kinase inhibitors. In this review, we provide an overview of recent advances in CADD and SMKIs and the application of CADD in the discovery of SMKIs.

Keywords

CADD LBDD SBDD kinase small molecule kinase inhibitors

References

  1. Curr Pharm Des. 2019;25(31):3339-3349 [PMID: 31480998]
  2. J Mol Model. 2015 Jun;21(6):156 [PMID: 26016942]
  3. Bioorg Med Chem. 2004 Dec 1;12(23):6183-91 [PMID: 15519162]
  4. Curr Pharm Des. 2012;18(20):2936-45 [PMID: 22571662]
  5. J Agric Food Chem. 2017 Apr 19;65(15):3204-3211 [PMID: 28358187]
  6. J Mol Recognit. 2013 May;26(5):215-39 [PMID: 23526775]
  7. J Med Chem. 2020 Jul 9;63(13):6679-6693 [PMID: 32250617]
  8. Biochemistry. 1989 Nov 28;28(24):9286-92 [PMID: 2558716]
  9. J Biomed Sci. 2011 Jan 21;18:8 [PMID: 21251245]
  10. J Mol Graph Model. 2011 Sep;30:54-66 [PMID: 21798777]
  11. Molecules. 2015 Jul 22;20(7):13384-421 [PMID: 26205061]
  12. Nature. 2018 Jul;559(7714):377-381 [PMID: 30022133]
  13. Future Med Chem. 2011 Jan;3(1):29-43 [PMID: 21428824]
  14. J Phys Chem B. 2012 Feb 16;116(6):1884-900 [PMID: 22239286]
  15. Cancer Res. 2008 Mar 15;68(6):1618-24 [PMID: 18339839]
  16. Leukemia. 2014 Feb;28(2):404-7 [PMID: 23823659]
  17. BMC Proc. 2013 Apr 04;7 Suppl 2:K15 [PMID: 24764472]
  18. PLoS Comput Biol. 2012;8(10):e1002704 [PMID: 23055911]
  19. Cancer. 2002 Jun 15;94(12):3127-34 [PMID: 12115344]
  20. Drug Discov Today. 2007 Sep;12(17-18):725-31 [PMID: 17826685]
  21. Trends Pharmacol Sci. 2012 May;33(5):273-8 [PMID: 22503441]
  22. Proteins. 2004 Jul 1;56(1):52-66 [PMID: 15162486]
  23. J Chem Inf Model. 2006 Jan-Feb;46(1):401-15 [PMID: 16426074]
  24. J Med Chem. 2019 Oct 24;62(20):8973-8995 [PMID: 31318208]
  25. Bioorg Med Chem Lett. 2015 Apr 1;25(7):1597-602 [PMID: 25736998]
  26. J Enzyme Inhib Med Chem. 2012 Dec;27(6):800-9 [PMID: 21981000]
  27. Eur J Med Chem. 2015 Feb 16;91:4-14 [PMID: 25108504]
  28. J Biol Chem. 1990 Nov 15;265(32):19728-35 [PMID: 1700979]
  29. Top Curr Chem. 2012;326:1-34 [PMID: 21915777]
  30. J Med Chem. 2018 Sep 27;61(18):8120-8135 [PMID: 30137981]
  31. Drug Discov Today. 2017 Aug;22(8):1216-1223 [PMID: 28689054]
  32. J Biol Chem. 2013 May 24;288(21):14673-80 [PMID: 23585568]
  33. Drug Discov Today. 2016 Jan;21(1):5-10 [PMID: 26210956]
  34. J Comput Aided Mol Des. 1995 Dec;9(6):532-49 [PMID: 8789195]
  35. Expert Opin Drug Discov. 2007 Aug;2(8):1085-101 [PMID: 23484874]
  36. Chem Biol. 2005 Jun;12(6):621-37 [PMID: 15975507]
  37. J Health Econ. 2016 May;47:20-33 [PMID: 26928437]
  38. Nat Chem Biol. 2006 Jul;2(7):358-64 [PMID: 16783341]
  39. J Neurochem. 2009 Oct;111(1):242-9 [PMID: 19659459]
  40. Mol Inform. 2020 Nov;39(11):e2000059 [PMID: 32578959]
  41. Nature. 2015 Dec 17;528(7582):370-5 [PMID: 26649818]
  42. Bioinformation. 2012;8(2):81-6 [PMID: 22359440]
  43. Cell. 1978 Oct;15(2):561-72 [PMID: 214242]
  44. Drug Discov Today Technol. 2004 Dec;1(3):253-60 [PMID: 24981493]
  45. J Chem Theory Comput. 2018 Oct 9;14(10):5273-5289 [PMID: 30176213]
  46. J Control Release. 2004 Sep 14;99(1):113-25 [PMID: 15342185]
  47. J Mol Graph Model. 2013 Mar;40:91-8 [PMID: 23353584]
  48. Curr Biol. 2002 Oct 29;12(21):1871-6 [PMID: 12419189]
  49. Curr Drug Targets. 2008 Dec;9(12):1062-70 [PMID: 19128216]
  50. ACS Omega. 2020 Jul 24;5(30):18662-18674 [PMID: 32775868]
  51. Trends Mol Med. 2009 Mar;15(3):112-9 [PMID: 19246243]
  52. Yakugaku Zasshi. 2010 Nov;130(11):1427-33 [PMID: 21048399]
  53. J Med Chem. 2004 Mar 25;47(7):1739-49 [PMID: 15027865]
  54. Nucleic Acids Res. 2010 Jul;38(Web Server issue):W445-9 [PMID: 20444869]
  55. Drug Discov Today. 2009 Jul;14(13-14):676-83 [PMID: 19422931]
  56. Chem Rev. 1996 Dec 19;96(8):3147-3176 [PMID: 11848856]
  57. J Comput Aided Mol Des. 2002 Dec;16(12):883-902 [PMID: 12825621]
  58. J Chem Inf Model. 2010 Jan;50(1):110-22 [PMID: 20030297]
  59. Arch Pharm Res. 2009 Apr;32(4):481-7 [PMID: 19407963]
  60. Chem Rev. 2001 Aug;101(8):2209-42 [PMID: 11749371]
  61. Drug Discov Today. 2007 Dec;12(23-24):1013-7 [PMID: 18061879]
  62. J Ethnopharmacol. 2014 Aug 8;155(1):589-98 [PMID: 24928828]
  63. Eur J Med Chem. 2021 Nov 15;224:113705 [PMID: 34303871]
  64. Proteins. 2003 Sep 1;52(4):609-23 [PMID: 12910460]
  65. Prog Chem Org Nat Prod. 2019;110:99-141 [PMID: 31621012]
  66. Comb Chem High Throughput Screen. 2006 Mar;9(3):213-28 [PMID: 16533155]
  67. Cent Nerv Syst Agents Med Chem. 2016;16(2):75-80 [PMID: 25687583]
  68. J Phys Chem B. 2016 Oct 27;120(42):10899-10922 [PMID: 27668950]
  69. Nucleosides Nucleotides Nucleic Acids. 2007;26(6-7):651-4 [PMID: 18066873]
  70. Curr Top Med Chem. 2009;9(8):738-53 [PMID: 19689378]
  71. J Mol Biol. 1996 Aug 23;261(3):470-89 [PMID: 8780787]
  72. J Chem Inf Model. 2017 Jan 23;57(1):73-84 [PMID: 27983849]
  73. J Phys Chem B. 2013 Dec 19;117(50):16096-104 [PMID: 24289143]
  74. Bioorg Med Chem. 2009 Dec 1;17(23):7861-71 [PMID: 19884012]
  75. Int J Mol Sci. 2011;12(5):2822-41 [PMID: 21686153]
  76. J Hazard Mater. 2015 Dec 15;299:260-79 [PMID: 26142156]
  77. J Mol Recognit. 2015 Oct;28(10):581-604 [PMID: 25808539]
  78. Proteins. 2003 Jul 1;52(1):80-7 [PMID: 12784371]
  79. Methods Mol Biol. 2012;841:291-319 [PMID: 22222458]
  80. Pharmaceuticals (Basel). 2022 May 23;15(5): [PMID: 35631472]
  81. Drug Des Devel Ther. 2017 Jun 22;11:1859-1870 [PMID: 28694686]
  82. Nat Rev Drug Discov. 2007 Jun;6(6):464-79 [PMID: 17541419]
  83. Drug Discov Today. 2020 Sep;25(9):1624-1638 [PMID: 32663517]
  84. J Med Chem. 2016 May 12;59(9):4035-61 [PMID: 26807648]
  85. Nat Rev Drug Discov. 2002 Jul;1(7):493-502 [PMID: 12120256]
  86. Eur J Med Chem. 2011 Mar;46(3):877-84 [PMID: 21277656]
  87. Drug Saf. 2001;24(15):1113-25 [PMID: 11772145]
  88. Drug Discov Today. 2023 Feb;28(2):103439 [PMID: 36372330]
  89. Chem Res Toxicol. 2011 Aug 15;24(8):1251-62 [PMID: 21699217]
  90. Curr Top Med Chem. 2008;8(18):1555-72 [PMID: 19075767]
  91. Nat Biotechnol. 2011 Oct 30;29(11):1046-51 [PMID: 22037378]
  92. J Comput Chem. 2010 Jan 30;31(2):455-61 [PMID: 19499576]
  93. Front Pharmacol. 2015 Aug 21;6:173 [PMID: 26347652]
  94. J Med Chem. 1989 Oct;32(10):2344-52 [PMID: 2552117]
  95. J Comput Aided Mol Des. 2017 Mar;31(3):255-266 [PMID: 27878643]
  96. Curr Drug Targets Infect Disord. 2002 Mar;2(1):93-102 [PMID: 12462157]
  97. Nature. 2018 Mar 28;555(7698):604-610 [PMID: 29595767]
  98. Circulation. 2012 Oct 9;126(15):1803-7 [PMID: 22972901]
  99. Phys Rev Lett. 1985 Nov 25;55(22):2471-2474 [PMID: 10032153]
  100. J Med Chem. 2003 Feb 13;46(4):499-511 [PMID: 12570372]
  101. J Med Chem. 2011 Jul 14;54(13):4638-58 [PMID: 21604762]
  102. J Enzyme Inhib Med Chem. 2016 Aug;31(4):608-18 [PMID: 26114307]
  103. J Chem Theory Comput. 2015 Jun 9;11(6):2398-411 [PMID: 26575540]
  104. J Comput Chem. 2003 Apr 30;24(6):760-9 [PMID: 12666168]
  105. Brain Res Brain Res Rev. 2000 Aug;33(1):95-130 [PMID: 10967355]
  106. J Agric Food Chem. 2023 Jun 14;71(23):8769-8777 [PMID: 37254716]
  107. Drug Discov Today. 2005 Jul 1;10(13):895-907 [PMID: 15993809]
  108. Drug Discov Today. 2017 Feb;22(2):249-269 [PMID: 27890821]
  109. Science. 2004 Mar 19;303(5665):1800-5 [PMID: 15031492]
  110. J Med Chem. 2020 Jan 9;63(1):52-65 [PMID: 31820981]
  111. Front Cell Dev Biol. 2021 Mar 04;9:649434 [PMID: 33748144]
  112. Curr Comput Aided Drug Des. 2011 Jun;7(2):146-57 [PMID: 21534921]
  113. Biochim Biophys Acta. 1998 Dec 8;1436(1-2):127-50 [PMID: 9838078]
  114. J Med Chem. 2000 Jun 29;43(13):2575-85 [PMID: 10891117]
  115. Clin Liver Dis. 2003 Feb;7(1):1-21, vii [PMID: 12691456]
  116. Angew Chem Int Ed Engl. 2016 May 10;55(20):5904-37 [PMID: 27062365]
  117. Methods Mol Biol. 2012;819:515-24 [PMID: 22183555]
  118. Chem Rev. 1996 May 9;96(3):1027-1044 [PMID: 11848779]
  119. Cell Host Microbe. 2009 Jan 22;5(1):23-34 [PMID: 19154985]
  120. Cell. 1992 Aug 7;70(3):419-29 [PMID: 1322797]
  121. Autoimmun Rev. 2010 Jan;9(3):148-52 [PMID: 19465164]
  122. Pharmacol Res. 2023 Jan;187:106552 [PMID: 36403719]
  123. Biopolymers. 2006 Jun 15;82(3):272-84 [PMID: 16508951]
  124. Drugs. 1996 Jul;52(1):93-112 [PMID: 8799687]
  125. Nat Rev Drug Discov. 2010 Apr;9(4):273-6 [PMID: 20357802]
  126. J Mol Model. 2012 Jan;18(1):171-86 [PMID: 21523553]
  127. BMC Biol. 2011 Oct 28;9:71 [PMID: 22035460]
  128. Drug Discov Today. 2010 Jun;15(11-12):444-50 [PMID: 20362693]
  129. J Chem Theory Comput. 2006 May;2(3):815-26 [PMID: 26626688]
  130. ACS Chem Biol. 2015 Jan 16;10(1):269-78 [PMID: 25420233]
  131. Curr Comput Aided Drug Des. 2011 Mar;7(1):10-22 [PMID: 20807187]
  132. J Am Chem Soc. 2002 May 22;124(20):5632-3 [PMID: 12010024]
  133. Eur J Med Chem. 2011 May;46(5):1648-55 [PMID: 21388719]
  134. Leukemia. 2003 Jun;17(6):1186-7 [PMID: 12764388]
  135. Nat Rev Drug Discov. 2021 Nov;20(11):839-861 [PMID: 34354255]
  136. Biopolymers. 2003 Jan;68(1):76-90 [PMID: 12579581]
  137. Adv Robot. 2015;29(13):817-829 [PMID: 27030786]
  138. Future Med Chem. 2020 Jun;12(12):1121-1136 [PMID: 32400188]
  139. Science. 1988 Nov 11;242(4880):933-5 [PMID: 3263702]
  140. Arterioscler Thromb Vasc Biol. 2011 Dec;31(12):2897-908 [PMID: 21940946]
  141. Comput Biol Chem. 2014 Oct;52:25-33 [PMID: 25179857]
  142. J Phys Chem A. 2017 Dec 28;121(51):9752-9763 [PMID: 29182862]
  143. Eur J Med Chem. 2012 Jan;47(1):38-43 [PMID: 22078765]
  144. J Chem Phys. 2007 May 7;126(17):174101 [PMID: 17492851]
  145. Eur J Pharm Sci. 2001 Jun;13(3):261-70 [PMID: 11384848]
  146. Adv Appl Bioinform Chem. 2016 Jun 28;9:1-11 [PMID: 27390530]
  147. Chem Soc Rev. 2009 Aug;38(8):2319-33 [PMID: 19623353]
  148. Chem Rev. 2015 Jun 24;115(12):5678-796 [PMID: 25853797]
  149. Mol Pain. 2005 Sep 02;1:25 [PMID: 16137337]
  150. Cell. 2007 Nov 2;131(3):476-91 [PMID: 17981116]
  151. PLoS Med. 2007 May;4(5):e154 [PMID: 17472434]
  152. Methods Mol Biol. 2008;443:365-82 [PMID: 18446297]
  153. Drug Discov Today. 2015 Jun;20(6):686-702 [PMID: 25615716]
  154. Trends Pharmacol Sci. 2015 Jul;36(7):422-39 [PMID: 25975227]
  155. Cancer Res. 1996 Mar 15;56(6):1253-5 [PMID: 8640809]
  156. Mol Endocrinol. 1996 May;10(5):488-98 [PMID: 8732680]
  157. Nucleic Acids Res. 1994 Nov 11;22(22):4673-80 [PMID: 7984417]
  158. RNA. 2009 Jun;15(6):1219-30 [PMID: 19369428]
  159. Nature. 2018 Jul;559(7715):547-555 [PMID: 30046072]
  160. Arch Pharm Res. 2015 Sep;38(9):1686-701 [PMID: 26208641]
  161. J Comput Aided Mol Des. 2002 Mar;16(3):151-66 [PMID: 12363215]
  162. J Chem Inf Model. 2020 Dec 28;60(12):5781-5793 [PMID: 32687345]
  163. Angew Chem Int Ed Engl. 2016 Sep 5;55(37):11139-43 [PMID: 27484830]
  164. J Chem Inf Comput Sci. 2003 Mar-Apr;43(2):545-53 [PMID: 12653520]
  165. Eur Phys J E Soft Matter. 2017 Feb;40(2):19 [PMID: 28229319]
  166. Cell. 2007 Jun 1;129(5):903-14 [PMID: 17540171]
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