Citation: Jiayue Tang, Meng Ou, Qiuling Zheng, Ya Ding. Unmodified methodologies in target discovery for small molecule drugs: A rising star[J]. Chinese Chemical Letters, ;2022, 33(12): 4980-4988. doi: 10.1016/j.cclet.2022.04.013 shu

Unmodified methodologies in target discovery for small molecule drugs: A rising star

Jiayue Tang ^a ,
Meng Ou ^a ,
Qiuling Zheng ^{b, *,} ,
Ya Ding ^{a, *,}

a.
Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing 210009, China
b.
State Key Laboratory of Natural Medicines, Department of Pharmaceutical Analysis, College of Pharmacy, China Pharmaceutical University, Nanjing 210009, China

qiuling_zheng@cpu.edu.cn

dingya@cpu.edu.cn

Received Date: 3 February 2022
Revised Date: 3 April 2022
Accepted Date: 6 April 2022
Available Online: 11 April 2022

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Target discovery, involving target identification and validation, is the prerequisite for drug discovery and screening. Novel methodologies and technologies for the precise discovery and confirmation of drug targets are powerful tools in understanding the disease, looking for a drug and elucidating the mechanism of drug treatment. Among the common target identification and confirmation methods, the modified method is time-consuming and laborious, which may reduce or change the activity of natural products. The unmodified methods developed in recent years without chemical modification have gradually become an important means of studying drug targets. A wide range of unmodified approaches have been reported, introducing and analyzing the recent emerging methodologies and technologies. This review highlights the advantages and limitations of these methods for the application of drug target discovery and presents an overview of their contributions to the target discovery of small molecule drugs. The application and future development trends of methodologies in target discovery are also prospected to provide a reference for drug target research.
- Target discovery,
- Target identification,
- Small molecule drug,
- Methodologies,
- Unmodified
1. [1]
  B. Raymer, S.K. Bhattacharya, J. Med. Chem. 61 (2018) 10375–10384. doi: 10.1021/acs.jmedchem.8b00407
2. [2]
  S.J. Dixon, B.R. Stockwell, Curr. Opin. Chem. Biol. 13 (2009) 549–555. doi: 10.1016/j.cbpa.2009.08.003
3. [3]
  J.G. Moffat, F. Vincent, J.A. Lee, J. Eder, M. Prunotto, Nat. Rev. Drug Discov. 16 (2017) 531–543. doi: 10.1038/nrd.2017.111
4. [4]
  S. Sakamoto, Y. Kabe, M. Hatakeyama, Y. Yamaguchi, H. Handa, Chem. Rec. 9 (2009) 66–85. doi: 10.1002/tcr.20170
5. [5]
  S. Sadegh, J. Matschinske, D.B. Blumenthal, Nat. Commun. 11 (2020) 3518. doi: 10.1038/s41467-020-17189-2
6. [6]
  J. Vamathevan, D. Clark, P. Czodrowski, Nat. Rev. Drug Discov. 18 (2019) 463–477. doi: 10.1038/s41573-019-0024-5
7. [7]
  C.L. Gao, G.G. Hou, J. Liu, Angew. Chem. Int. Ed. 59 (2020) 2429–2439. doi: 10.1002/anie.201912489
8. [8]
  G.V. Paolini, R.H.B. Shapland, W.P. van Hoorn, J.S. Mason, A.L. Hopkins, Nat. Biotechnol. 24 (2006) 805–815. doi: 10.1038/nbt1228
9. [9]
  X. Chen, Y. Wang, N. Ma, Signal Transduct. Targeted Ther. 5 (2020) 72. doi: 10.1117/12.2575904
10. [10]
  A.C.M. van Esbroeck, A.P.A. Janssen, A.B. Cognetta, Science 356 (2017) 1084–1087. doi: 10.1126/science.aaf7497
11. [11]
  Z. Slava, P. Verena, H. Christian, W. Herbert, Angew. Chem. Int. Ed. 52 (2013) 2744–2792. doi: 10.1002/anie.201208749
12. [12]
  J. Du, J. Guo, D. Kang, Chin. Chem. Lett. 31 (2020) 1695–1708. doi: 10.1016/j.cclet.2020.03.028
13. [13]
  Z. Yuan, M. Chen, J. Wang, Fish Shellfish Immunol. 79 (2018) 130–139. doi: 10.1016/j.fsi.2018.05.003
14. [14]
  D.E. Gordon, G.M. Jang, M. Bouhaddou, Nature 583 (2020) 459–468. doi: 10.1038/s41586-020-2286-9
15. [15]
  H. Deng, Q. Lei, Y. Wu, Y. He, W. Li, Eur. J. Med. Chem. 191 (2020) 112151. doi: 10.1016/j.ejmech.2020.112151
16. [16]
  J. Xu, X. Li, K. Ding, Z. Li, Chem. Asian J. 15 (2020) 34–41. doi: 10.1002/asia.201901500
17. [17]
  J. Wang, Q. Chen, Y. Shan, X. Pan, J. Zhang, Trends Anal. Chem. 115 (2019) 110–120. doi: 10.1016/j.trac.2019.03.028
18. [18]
  L. Li, Y. Zhao, R. Cao, Chem. Commun. 55 (2019) 4407–4410. doi: 10.1039/c9cc00917e
19. [19]
  J. Huang, H. Zhu, S.J. Haggarty, Proc. Natl. Acad. Sci. U. S. A. 101 (2004) 16594–16599. doi: 10.1073/pnas.0407117101
20. [20]
  D. Xia, B. Liu, X. Xu, Y. Ding, Q. Zheng, J. Pharm. Anal. 11 (2021) 121–127.
21. [21]
  X. Tu, X. Tan, X. Qi, J. Nanobiotechnol. 18 (2020) 32. doi: 10.1186/s12951-020-00591-9
22. [22]
  B.L. Liu, H.C. Zhang, Y. Ding, Chin. Chem. Lett. 29 (2018) 1725–1730. doi: 10.1016/j.cclet.2018.12.006
23. [23]
  Z.Q. Shi, Q.Q. Li, L. Mei, Chin. Chem. Lett. 31 (2020) 1345–1356. doi: 10.1016/j.cclet.2020.03.001
24. [24]
  W.J. Wang, J. Wang, Y. Ding, J. Mater. Chem. B 8 (2020) 4813–4830. doi: 10.1039/c9tb02924a
25. [25]
  J. Chang, Y. Kim, H.J. Kwon, Nat. Prod. Rep. 33 (2016) 719–730. doi: 10.1039/C5NP00107B
26. [26]
  B. Lomenick, R. Hao, N. Jonai, Proc. Natl. Acad. Sci. U. S. A. 106 (2009) 21984–21989. doi: 10.1073/pnas.0910040106
27. [27]
  M. Pepelnjak, N. de Souza, P. Picotti, Trends Biochem. Sci. 45 (2020) 919–920. doi: 10.1016/j.tibs.2020.05.006
28. [28]
  E.C. Strickland, M.A. Geer, D.T. Tran, Nat. Protoc. 8 (2013) 148–161. doi: 10.1038/nprot.2012.146
29. [29]
  D.M. Molina, R. Jafari, M. Ignatushchenko, Science 341 (2013) 84–87. doi: 10.1126/science.1233606
30. [30]
  B. Lomenick, R.W. Olsen, J. Huang, ACS Chem. Biol. 6 (2011) 34–46. doi: 10.1021/cb100294v
31. [31]
  J. Huang, B.E. Lomenick, R. Hao, Patent, US8703438 (B2), 2014.
32. [32]
  F. Dal Piaz, M.B. Vera Saltos, S. Franceschelli, et al., J. Nat. Prod. 79 (2016) 2681–2692. doi: 10.1021/acs.jnatprod.6b00627
33. [33]
  Q. Li, L. Cao, Y. Tian, Mol. Cell. Proteom. 17 (2018) 1531–1545. doi: 10.1074/mcp.ra118.000752
34. [34]
  B. Lomenick, G. Jung, J.A. Wohlschlegel, J. Huang, Curr. Protoc. Cell Biol. 3 (2011) 163–180. doi: 10.1002/9780470559277.ch110180
35. [35]
  R. Su, L. Dong, C. Li, Cell 172 (2018) 90–105. doi: 10.1016/j.cell.2017.11.031
36. [36]
  J.J. Chen, R. Su, Patent, US11179360 (B2), 2021.
37. [37]
  Y. Huang, R. Su, Y. Sheng, Cancer Cell 35 (2019) 677–691. doi: 10.1016/j.ccell.2019.03.006
38. [38]
  R. Su, L. Dong, Y. Li, Cancer Cell 38 (2020) 79–96. doi: 10.1016/j.ccell.2020.04.017
39. [39]
  Y. Yang, L. Cao, H. Gao, J. Med. Chem. 62 (2019) 4056–4073. doi: 10.1021/acs.jmedchem.9b00091
40. [40]
  D. Minond, G.B. Fields, M. Giulianotti, Patent, US11149028 (B2), 2021.
41. [41]
  P. Leuenberger, S. Ganscha, A. Kahraman, Science 355 (2017) eaai7825. doi: 10.1126/science.aai7825
42. [42]
  Y. Feng, G. De Franceschi, A. Kahraman, Nat. Biotechnol. 32 (2014) 1036–1044. doi: 10.1038/nbt.2999
43. [43]
  I. Piazza, K. Kochanowski, V. Cappelletti, Cell 172 (2018) 358–372. doi: 10.1016/j.cell.2017.12.006
44. [44]
  S. Schopper, A. Kahraman, P. Leuenberger, Nat. Protoc. 12 (2017) 2391–2410. doi: 10.1038/nprot.2017.100
45. [45]
  P. Nordlund, Patent, US9528996 (B2), 2016.
46. [46]
  T. Friman, Biorg. Med. Chem. 28 (2020) 115174. doi: 10.1016/j.bmc.2019.115174
47. [47]
  T.P. Miettinen, M. Bjorklund, Mol. Pharm. 11 (2014) 4395–4404. doi: 10.1021/mp5004866
48. [48]
  T. Ishii, T. Okai, M. Iwatani-Yoshihara, Sci. Rep. 7 (2017) 13000. doi: 10.1038/s41598-017-12513-1
49. [49]
  M.M. Savitski, F.B.M. Reinhard, H. Franken, Science 346 (2014) 1255784. doi: 10.1126/science.1255784
50. [50]
  H. Franken, T. Mathieson, D. Childs, Nat. Protoc. 10 (2015) 1567–1593. doi: 10.1038/nprot.2015.101
51. [51]
  F.B.M. Reinhard, D. Eberhard, T. Werner, Nat. Methods 12 (2015) 1129–1134. doi: 10.1038/nmeth.3652
52. [52]
  C. Ruan, W. Ning, Z. Liu, ACS Chem. Biol. 17 (2022) 252–262. doi: 10.1021/acschembio.1c00936
53. [53]
  M.L. Ye, J.W. Lv, Patent, CN114076826 (A), 2022.
54. [54]
  J. Dziekan, H. Yu, D. Chen, Sci. Transl. Med. 11 (2019) eaau3174. doi: 10.1126/scitranslmed.aau3174
55. [55]
  K.Y. Lu, B. Quan, K. Sylvester, Proc. Natl. Acad. Sci. U. S. A. 117 (2020) 5810–5817. doi: 10.1073/pnas.1913525117
56. [56]
  V.C. Kirsch, C. Orgler, S. Braig, Angew. Chem. Int. Ed. 59 (2020) 1595–1600. doi: 10.1002/anie.201911158
57. [57]
  G.M. West, L. Tang, M.C. Fitzgerald, Anal. Chem. 80 (2008) 4175–4185. doi: 10.1021/ac702610a
58. [58]
  E.J. Walker, J.Q. Bettinger, K.A. Welle, J.R. Hryhorenko, S. Ghaemmaghami, Proc. Natl. Acad. Sci. U. S. A. 116 (2019) 6081–6090. doi: 10.1073/pnas.1819851116
59. [59]
  A. Cabrera, N. Wiebelhaus, B. Quan, J. Am. Soc. Mass Spectrom. 31 (2020) 217–226. doi: 10.1021/jasms.9b00041
60. [60]
  P.D. Dearmond, Y. Xu, E.C. Strickland, K.G. Daniels, M.C. Fitzgerald, J. Proteome Res. 10 (2011) 4948–4958. doi: 10.1021/pr200403c
61. [61]
  R.N. Ogburn, L. Jin, H. Meng, M.C. Fitzgerald, J. Proteome Res. 16 (2017) 4073–4085. doi: 10.1021/acs.jproteome.7b00442
62. [62]
  H. Meng, R. Ma, M.C. Fitzgerald, Anal. Chem. 90 (2018) 9249–9255. doi: 10.1021/acs.analchem.8b01772
63. [63]
  X. Zhang, Q. Wang, Y. Li, Anal. Chem. 92 (2020) 1363–1371. doi: 10.1021/acs.analchem.9b04531
64. [64]
  M. Miyagi, K. Tanaka, S. Watanabe, J. Kondo, T. Kishimoto, Anal. Chem. 93 (2021) 14985–14995. doi: 10.1021/acs.analchem.1c02283
65. [65]
  J. Lyu, Y. Wang, C. Ruan, Anal. Chim. Acta 1168 (2021) 338612. doi: 10.1016/j.aca.2021.338612
66. [66]
  H.Y. Hwang, T.Y. Kim, M.A. Szasz, Proteomics 20 (2020) e1900325. doi: 10.1002/pmic.201900325
1. [1]
  TIAN Ran , LIU Zhen-Ming , JIN Hong-Wei , ZHANG Liang-Ren , LIN Wen-Han . Target Identification of Isomalabaricane Terpenes Extracted from Sponges. Acta Physico-Chimica Sinica, 2011, 27(05): 1214-1222. doi: 10.3866/PKU.WHXB20110525
2. [2]
  Wang Ting , Deng Yu , Qu Guanwen , Chen Yaozhong , Shang Jing , Feng Zhangqi , Zheng Jie , Yang Fengyu , He Nongyue . Cell microarray chip system for accurate, rapid diagnosis and target treatment of breast cancer cells SK-BR-3. Chinese Chemical Letters, 2019, 30(5): 1043-1050. doi: 10.1016/j.cclet.2019.01.011
3. [3]
  Deng Haohua , He Shaobin , Lin Xiuling , Yang Lu , Lin Zhen , Chen Ruiting , Peng Huaping , Chen Wei . Target-triggered inhibiting oxidase-mimicking activity of platinum nanoparticles for ultrasensitive colorimetric detection of silver ion. Chinese Chemical Letters, 2019, 30(9): 1659-1662. doi: 10.1016/j.cclet.2019.05.032
4. [4]
  Du Jintong , Guo Jing , Kang Dongwei , Li Zhihong , Wang Guan , Wu Jianbing , Zhang Zhen , Fang Hao , Hou Xuben , Huang Zhangjian , Li Guobo , Lu Xiaoyun , Liu Xinyong , Ouyang Liang , Rao Li , Zhan Peng , Zhang Xiaojin , Zhang Yihua . New techniques and strategies in drug discovery. Chinese Chemical Letters, 2020, 31(7): 1695-1708. doi: 10.1016/j.cclet.2020.03.028
5. [5]
  Jiafu Chang , Wenxin Lv , Jiahui Wu , Haiyin Li , Feng Li . Simultaneous photoelectrochemical detection of dual microRNAs by capturing CdS quantum dots and methylene blue based on target-initiated strand displaced amplification. Chinese Chemical Letters, 2021, 32(2): 775-778. doi: 10.1016/j.cclet.2020.05.041
6. [6]
  Fenfen Zhou , Yanli Zhou , Jianwei Zhang , Hui Dong , Lantao Liu , Yintang Zhang , Maotian Xu . Target-induced mimic enzyme deactivation based on mixed-node metal-organic frameworks for colorimetric assay of hydrogen sulfide. Chinese Chemical Letters, 2021, 32(10): 3155-3158. doi: 10.1016/j.cclet.2021.02.053
7. [7]
  Zhao Jiaoyan , Jiang Xuefeng . The application of sulfur-containing peptides in drug discovery. Chinese Chemical Letters, 2018, 29(7): 1079-1087. doi: 10.1016/j.cclet.2018.05.026
8. [8]
  Hacer Karatas , Shirley Y. Lee , Elizabeth C. Townsend , Fang Cao , Jing Xu , Denzil Bernard , Liu Liu , Yali Dou , Shaomeng Wang . Structure-based design of conformationally constrained cyclic peptidomimetics to target the MLL1-WDR5 protein-protein interaction as inhibitors of the MLL1 methyltransferase activity. Chinese Chemical Letters, 2015, 26(4): 455-458. doi: 10.1016/j.cclet.2015.03.030
9. [9]
  Ren Yue , Sun Qinsheng , Yuan Zigao , Jiang Yuyang . Combined inhibition of HDAC and DNMT1 induces p85α/MEKmediated cell cycle arrest by dual target inhibitor 208 in U937 cells. Chinese Chemical Letters, 2019, 30(6): 1233-1236. doi: 10.1016/j.cclet.2019.03.029
10. [10]
  Jiaqi Deng , Jingyuan Xu , Minzhi Ouyang , Zhen Zou , Yanli Lei , Junbin Li , Zhihe Qing , Ronghua Yang . Target-triggered hairpin-free chain-branching growth of DNA dendrimers for contrast-enhanced imaging in living cells by avoiding signal dispersion. Chinese Chemical Letters, 2022, 33(2): 773-777. doi: 10.1016/j.cclet.2021.08.046
11. [11]
  Cai-Hong Wang , Cai-Sheng Wu , Hai-Lin Qin , Jin-Lan Zhang . Rapid discovery and identification of 68 compounds in the active fraction from Xiao-Xu-Ming decoction (XXMD) by HPLC-HRMS and MTSF technique. Chinese Chemical Letters, 2014, 25(12): 1648-1652. doi: 10.1016/j.cclet.2014.09.001
12. [12]
  Qin Wenjing , Xu Chenchen , Zhao Yanfei , Yu Changmin , Shen Sheng , Li Lin , Huang Wei . Recent progress in small molecule fluorescent probes for nitroreductase. Chinese Chemical Letters, 2018, 29(10): 1451-1455. doi: 10.1016/j.cclet.2018.04.007
13. [13]
  Hu Guodong , Jia Huiyi , Zhao Lanning , Cho Dong-Hyung , Fang Jianguo . Small molecule fluorescent probes of protein vicinal dithiols. Chinese Chemical Letters, 2019, 30(10): 1704-1716. doi: 10.1016/j.cclet.2019.06.039
14. [14]
  Liu Jing , Chen Qi-Wei , Wu Kai . On-surface construction of low-dimensional nanostructures with terminal alkynes: Linking strategies and controlling methodologies. Chinese Chemical Letters, 2017, 28(8): 1631-1639. doi: 10.1016/j.cclet.2017.04.022
15. [15]
  Yu Wang , Dian-Ming Zhou , Zhan Wu , Li-Juan Tang , Jian-Hui Jiang . Terminal protection of small molecule-linked ssDNA-SWNT nanoassembly for sensitive detection of small molecule and protein interaction. Chinese Chemical Letters, 2013, 24(2): 107-110.
16. [16]
  Li Ying , Cao Xiuxiu , Tian Changlin , Zheng Ji-Shen . Chemical protein synthesis-assisted high-throughput screening strategies for D-peptides in drug discovery. Chinese Chemical Letters, 2020, 31(9): 2365-2374. doi: 10.1016/j.cclet.2020.04.015
17. [17]
  Yan-Ping Li , Ling Jiang , Tao Zhang , Ming Lin , Dan-Bi Tian , He Huang . Colorimetric detection of glucose using a boronic acid derivative receptor attached to unmodified AuNPs. Chinese Chemical Letters, 2014, 25(1): 77-79.
18. [18]
  Xuan Zhang , Xu-Dong Li . Solvent atmosphere controlled self-assembly of unmodified C60：A facile approach for constructing various architectures. Chinese Chemical Letters, 2014, 25(6): 912-914. doi: 10.1016/j.cclet.2014.03.041
19. [19]
  Xiao-Dong Xia , Tian-Lun Wang , Xiao-Yuan Yuan . Tuning plasmon absorption of unmodified silver nanoplates for sensitive and selective detection of copper ions by introduction of ascorbate. Chinese Chemical Letters, 2014, 25(10): 1403-1406. doi: 10.1016/j.cclet.2014.05.033
20. [20]
  . Novel colorimetric sensor for mercury (II) based on layer-by-layer assembly of unmodified silver triangular nanoplates. Chinese Chemical Letters, 2016, 27(10): 1635-1640. doi: 10.1016/j.cclet.2016.05.008

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