Citation: Jiawei Zhu, Yucheng Xiong, Xiaoxue Bai, Chenlong Xie, Baichen Xiong, Yao Chen, Haopeng Sun. Small molecule-drug conjugates: Mechanistic insights and strategic design for enhanced cancer therapy[J]. Chinese Chemical Letters, ;2025, 36(10): 110799. doi: 10.1016/j.cclet.2024.110799 shu

Small molecule-drug conjugates: Mechanistic insights and strategic design for enhanced cancer therapy

Jiawei Zhu ^a ,
Yucheng Xiong ^a ,
Xiaoxue Bai ^a ,
Chenlong Xie ^a ,
Baichen Xiong ^a ,
Yao Chen ^{b, *,} ,
Haopeng Sun ^{a, *,}

a.
School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China
b.
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China

300630@njucm.edu.cn

sunhaopeng@163.com

Received Date: 28 October 2024
Revised Date: 23 December 2024
Accepted Date: 24 December 2024
Available Online: 25 December 2024

Figures(15)

The evolution of cancer therapies has highlighted the limitations of traditional chemotherapy, particularly its lack of specificity and off-target toxicities, driving the development of targeted treatments like small molecule-drug conjugates (SMDCs). SMDCs offer distinct advantages over antibody-drug conjugates (ADCs), including simpler synthesis, lower production costs, and improved solid tumor penetration due to their smaller size. However, challenges remain, such as a limited variety of targeting ligands and the complexity of optimizing selectivity and efficacy within the tumor microenvironment. This review focuses on key aspects such as mechanisms of action, biomarker selection, and the optimization of each component of SMDCs. It also covers SMDCs that have been approved or are currently under active clinical trials, while providing insights into future developments in this promising field of targeted cancer therapies.
- Small molecule-drug conjugates,
- Targeted cancer therapy,
- Drug design strategy,
- Targeting ligands,
- Payloads,
- Linkers
1. [1]
  B.A. Chabner, T.G. Roberts, Nat. Rev. Cancer 5 (2005) 65–72. doi: 10.1038/nrc1529
2. [2]
  A.A.M. Van Der Veldt, M. Lubberink, R.H.J. Mathijssen, et al., Clin. Cancer Res. 19 (2013) 4163–4173. doi: 10.1158/1078-0432.CCR-12-3779
3. [3]
  L. Mosca, A. Ilari, F. Fazi, et al., Drug Resist. Updat. 54 (2021) 100742. doi: 10.1016/j.drup.2020.100742
4. [4]
  B. Kalyanaraman, Redox Biol. 29 (2020) 101394. doi: 10.1016/j.redox.2019.101394
5. [5]
  R.K. Singh, S. Kumar, D.N. Prasad, T.R. Bhardwaj, Eur. J. Med. Chem. 151 (2018) 401–433. doi: 10.1016/j.ejmech.2018.04.001
6. [6]
  S. Zhang, X. Liu, T. Bawa-Khalfe, et al., Nat. Med. 18 (2012) 1639–1642. doi: 10.1038/nm.2919
7. [7]
  M.T. Manzari, Y. Shamay, H. Kiguchi, et al., Nat. Rev. Mater. 6 (2021) 351–370. doi: 10.1038/s41578-020-00269-6
8. [8]
  E. Ortega-Forte, A. Rovira, A. Gandioso, et al., J. Med. Chem. 64 (2021) 17209–17220. doi: 10.1021/acs.jmedchem.1c01254
9. [9]
  X. Sheng, X. Yan, L. Wang, et al., Clin. Cancer Res. 27 (2021) 43–51. doi: 10.1158/1078-0432.ccr-20-2488
10. [10]
  J.P. Sharman, M. Egyed, W. Jurczak, et al., Lancet 395 (2020) 1278–1291. doi: 10.1016/S0140-6736(20)30262-2
11. [11]
  R.S. Herbst, G. Giaccone, F. De Marinis, et al., N. Engl. J. Med. 383 (2020) 1328–1339. doi: 10.1056/nejmoa1917346
12. [12]
  N. Krall, F. Pretto, W. Decurtins, et al., Angew. Chem. Int. Ed. 53 (2014) 4231–4235. doi: 10.1002/anie.201310709
13. [13]
  J.M. Lambert, R.V.J. Chari, J. Med. Chem. 57 (2014) 6949–6964. doi: 10.1021/jm500766w
14. [14]
  P. Tarantino, R. Carmagnani Pestana, C. Corti, et al., CA Cancer J. Clin. 72 (2022) 165–182. doi: 10.3322/caac.21705
15. [15]
  K.J. Norsworthy, C.W. Ko, J.E. Lee, et al., Oncologist 23 (2018) 1103–1108. doi: 10.1634/theoncologist.2017-0604
16. [16]
  K. Liu, M. Li, Y. Li, et al., Mol. Cancer 23 (2024) 62. doi: 10.1186/s12943-024-01963-7
17. [17]
  M. Senior, Nat. Biotechnol. 42 (2024) 362–366. doi: 10.1038/s41587-024-02168-5
18. [18]
  C.Do Pazo, K. Nawaz, R.M. Webster, Nat. Rev. Drug Discov. 20 (2021) 583–584. doi: 10.1038/d41573-021-00054-2
19. [19]
  T. Doi, K. Shitara, Y. Naito, et al., Lancet Oncol. 18 (2017) 1512–1522. doi: 10.1016/S1470-2045(17)30604-6
20. [20]
  Y.A. Heo, Drugs 83 (2023) 265–273. doi: 10.1007/s40265-023-01834-3
21. [21]
  R. Bartsch, A.S. Berghoff, J. Furtner, et al., Nat. Med. 28 (2022) 1840–1847. doi: 10.1038/s41591-022-01935-8
22. [22]
  G. Casi, D. Neri, J. Med. Chem. 58 (2015) 8751–8761. doi: 10.1021/acs.jmedchem.5b00457
23. [23]
  A. Zana, A. Galbiati, E. Gilardoni, et al., Clin. Cancer Res. 28 (2022) 5440–5454. doi: 10.1158/1078-0432.ccr-22-1788
24. [24]
  C.F. Lo, T.Y. Chiu, Y.T. Liu, et al., J. Med. Chem. 65 (2022) 12802–12824. doi: 10.1021/acs.jmedchem.2c00631
25. [25]
  K. Evans, J. Duan, T. Pritchard, et al., Clin. Cancer Res. 25 (2019) 4493–4503. doi: 10.1158/1078-0432.ccr-19-0551
26. [26]
  M.S. Dennis, H. Jin, D. Dugger, et al., Cancer Res. 67 (2007) 254–261. doi: 10.1158/0008-5472.CAN-06-2531
27. [27]
  J. Yang, J. Han, Y. Zhang, et al., Front. Pharmacol. 13 (2022) 924126. doi: 10.3389/fphar.2022.924126
28. [28]
  B. Oller-Salvia, G. Kym, J.W. Chin, Angew. Chem. Int. Ed. 57 (2018) 2831–2834. doi: 10.1002/anie.201712370
29. [29]
  F. Sun, T. Wang, J. Jiang, et al., Oncotarget 8 (2017) 51238–51252. doi: 10.18632/oncotarget.17228
30. [30]
  P. Dennler, A. Chiotellis, E. Fischer, et al., Bioconjug. Chem. 25 (2014) 569–578. doi: 10.1021/bc400574z
31. [31]
  G. Shah, S. Giralt, P. Dahi, et al., Blood Rev. 64 (2024) 101162. doi: 10.1016/j.blre.2023.101162
32. [32]
  U.S. Food and Drug Administration, https://www.fda.gov/drugs/resourcesinformation-approved-drugs/fda-approves-melphalan-liver-directedtreatment-uveal-melanoma.
33. [33]
  U.S. Food and Drug Administration, https://www.fda.gov/drugs/first-generic-drug-approvals/2020-first-generic-drug-approvals.
34. [34]
  B. Wang, F. Qi, P. Chen, et al., Int. J. Biol. Sci. 20 (2024) 1634–1651. doi: 10.7150/ijbs.92211
35. [35]
  J. Deng, S.B. Chernikova, Y. Wang, et al., Mol. Cancer Ther. 20 (2021) 2110–2116. doi: 10.1158/1535-7163.mct-21-0140
36. [36]
  M. Srinivasarao, P.S. Low, Chem. Rev. 117 (2017) 12133–12164. doi: 10.1021/acs.chemrev.7b00013
37. [37]
  D.A. Proia, D.L. Smith, J. Zhang, et al., Mol. Cancer Ther. 14 (2015) 2422–2432. doi: 10.1158/1535-7163.MCT-15-0455
38. [38]
  T.U. Amin, R. Emara, A. Pal, et al., J. Med. Chem. 65 (2022) 15473–15486. doi: 10.1021/acs.jmedchem.2c01423
39. [39]
  H.G. Lerchen, B. Stelte-Ludwig, C. Kopitz, et al., Cancers 14 (2022) 391. doi: 10.3390/cancers14020391
40. [40]
  A.D. Hobson, J. Xu, D.S. Welch, et al., J. Med. Chem. 66 (2023) 12544–12558. doi: 10.1021/acs.jmedchem.3c01174
41. [41]
  C.P. Guise, M.R. Abbattista, R.S. Singleton, et al., Cancer Res. 70 (2010) 1573–1584.
42. [42]
  F. Meng, W.F. Li, D. Jung, et al., Am. J. Cancer Res. (2021) 3645–3659.
43. [43]
  Y. Zheng, R. Xu, H. Cheng, et al., Mol. Ther. 32 (2024) 1048–1060. doi: 10.1016/j.ymthe.2024.02.020
44. [44]
  M. Stanbrough, G.J. Bubley, K. Ross, et al., Cancer Res. 66 (2006) 2815–2825. doi: 10.1158/0008-5472.CAN-05-4000
45. [45]
  T. Yoda, K. Kikuchi, Y. Miki, et al., Mol. Cell. Endocrinol. 413 (2015) 236–247. doi: 10.1016/j.mce.2015.07.008
46. [46]
  A.M. Tsimberidou, C.F. Verschraegen, R. Wesolowski, et al., Br. J. Cancer 129 (2023) 266–274. doi: 10.1038/s41416-023-02280-4
47. [47]
  R. Yan, Y. Li, J. Müller, et al., Cell Discov. 7 (2021) 16.
48. [48]
  C.P. Leamon, I.R. Vlahov, J.A. Reddy, et al., Bioconjug. Chem. 25 (2014) 560–568. doi: 10.1021/bc400441s
49. [49]
  J. Bendell, G. Falchook, S. Sen, et al., Ann. Oncol. 30 (2019) 172.
50. [50]
  B. Stelte-Ludwig, M.M. Frigault, H.G. Lerchen, et al., Cancer Res. 83 (2023) 484. doi: 10.1158/1538-7445.am2023-484
51. [51]
  S. Chen, X. Zhao, J. Chen, et al., Bioconjug. Chem. 21 (2010) 979–987. doi: 10.1021/bc9005656
52. [52]
  J. Ge, E. Normant, J.R. Porter, et al., J. Med. Chem. 49 (2006) 4606–4615. doi: 10.1021/jm0603116
53. [53]
  P.F. Chiu, C.K. Chang, P.S. Huang, et al., J. Med. Chem. 66 (2023) 9684–9696. doi: 10.1021/acs.jmedchem.3c00476
54. [54]
  P. Sapra, H. Zhao, M. Mehlig, et al., Clin. Cancer Res. 14 (2008) 1888–1896. doi: 10.1158/1078-0432.CCR-07-4456
55. [55]
  H.G. Lerchen, B. Stelte-Ludwig, M. Heroult, et al., Cancers 15 (2023) 4381. doi: 10.3390/cancers15174381
56. [56]
  C. Kratochwil, W. Fendler, M. Eiber, et al., Eur. J. Nucl. Med. Mol. Imaging 50 (2023) 2830–2845. doi: 10.1007/s00259-023-06255-8
57. [57]
  A. Mullard, Nat. Rev. Drug Discov. 23 (2024) 88–95. doi: 10.1038/d41573-024-00001-x
58. [58]
  X. Wang, J. Zhang, K. Zheng, et al., J. Pharm. Anal. 13 (2023) 776–787. doi: 10.1016/j.jpha.2023.02.010
59. [59]
  O.C. Kulterer, S. Pfaff, W. Wadsak, et al., J. Nucl. Med. 62 (2021) 360–365. doi: 10.2967/jnumed.120.245530
60. [60]
  M. Corpetti, C. Müller, H. Beltran, et al., Eur. Urol. 85 (2024) 193–204. doi: 10.1016/j.eururo.2023.11.018
61. [61]
  S.J. Park, B.H. Yoon, S.K. Kim, S.Y. Kim, BMC Med. Genomics 12 (2019) 101. doi: 10.1186/s12920-019-0514-7
62. [62]
  U.A. Matulonis, D. Lorusso, A. Oaknin, et al., J. Clin. Oncol. 41 (2023) 2436–2445. doi: 10.1200/jco.22.01900
63. [63]
  M. Chen, L. Cai, Y. Xiang, et al., Bioorg. Chem. 141 (2023) 106889. doi: 10.1016/j.bioorg.2023.106889
64. [64]
  G.M. Van Dam, G. Themelis, L.M.A. Crane, et al., Nat. Med. 17 (2011) 1315–1319. doi: 10.1038/nm.2472
65. [65]
  Y. Yuan, D.A. Nymoen, H.P. Dong, et al., Hum. Pathol. 40 (2009) 1453–1460. doi: 10.1016/j.humpath.2009.02.013
66. [66]
  R. Cé, G.K. Couto, B.Z. Pacheco, et al., Eur. J. Pharm. Sci. 165 (2021) 105943. doi: 10.1016/j.ejps.2021.105943
67. [67]
  N. Parakasikron, C. Chaotham, P. Chanvorachote, et al., Drug Deliv. 28 (2021) 1443–1454. doi: 10.1080/10717544.2021.1943055
68. [68]
  X. Li, S. Zhou, C.L. Abrahams, et al., Mol. Cancer Ther. 22 (2023) 155–167.
69. [69]
  S. Karan, M.Y. Cho, H. Lee, et al., J. Med. Chem. 64 (2021) 2971–2981. doi: 10.1021/acs.jmedchem.0c02162
70. [70]
  Q.R.J.G. Tummers, C.E.S. Hoogstins, K.N. Gaarenstroom, et al., Oncotarget 7 (2016) 32144–32155. doi: 10.18632/oncotarget.8282
71. [71]
  Y. Liu, Y. Chen, J. Jiang, et al., Eur. J. Med. Chem. 247 (2023) 115013. doi: 10.1016/j.ejmech.2022.115013
72. [72]
  Y. Nakamura, P.J. Hornsby, P. Casson, et al., J. Clin. Endocrinol. Metab. 94 (2009) 2192–2198. doi: 10.1210/jc.2008-2374
73. [73]
  K. Furuuchi, K. Rybinski, J. Fulmer, et al., Cancer Sci. 112 (2021) 2467–2480. doi: 10.1111/cas.14898
74. [74]
  X. Wu, J. Wu, J. Dai, et al., Natl. Sci. Rev. 8 (2021) nwaa306. doi: 10.1093/nsr/nwaa306
75. [75]
  J.A. Cornwell, A. Crncec, M.M. Afifi, et al., Nature 619 (2023) 363–370. doi: 10.1038/s41586-023-06274-3
76. [76]
  S.M. Gross, F. Mohammadi, C. Sanchez-Aguila, et al., Nat. Commun. 14 (2023) 3450. doi: 10.1038/s41467-023-39122-z
77. [77]
  D.I. Krijbolder, M. Verstappen, B.T. Van Dijk, et al., Lancet 400 (2022) 283–294. doi: 10.1016/S0140-6736(22)01193-X
78. [78]
  Y.H. Ling, C. Tornos, R. Perez-Soler, et al., J. Biol. Chem. 273 (1998) 18984–18991. doi: 10.1074/jbc.273.30.18984
79. [79]
  O. Tounekti, G. Pron, J. Belehradek, et al., Cancer Res. 53 (1993) 5462–5469.
80. [80]
  M. Shi, J. Hou, S. Shao, et al., Int. J. Mol. Sci. 24 (2023) 2498. doi: 10.3390/ijms24032498
81. [81]
  S. Dhillon, Drugs 81 (2021) 963–969. doi: 10.1007/s40265-021-01522-0
82. [82]
  Z. Liang, Y. Chen, Z. Wang, et al., J. Adv. Res. 40 (2022) 249–261. doi: 10.1016/j.jare.2021.12.007
83. [83]
  L.A. Korde, M.R. Somer, E.S. Hwang, et al., J. Clin. Oncol. 39 (2021) 1485–1505. doi: 10.1200/jco.20.03399
84. [84]
  D. Thomas, A.K. Rathinavel, P. Radhakrishnan, et al., Biochim. Biophys. Acta Rev. Cancer 1875 (2021) 188464. doi: 10.1016/j.bbcan.2020.188464
85. [85]
  V.K. Sarhadi, G. Armengol, Biomolecules 12 (2022) 1021. doi: 10.3390/biom12081021
86. [86]
  L. Whitesell, S.L. Lindquist, Nat. Rev. Cancer 5 (2005) 761–772. doi: 10.1038/nrc1716
87. [87]
  Y. Kanai, Pharmacol. Ther. 230 (2022) 107964. doi: 10.1016/j.pharmthera.2021.107964
88. [88]
  T. Ozawa, M. Rodriguez, G. Zhao, et al., Cureus 13 (2021) e17595.
89. [89]
  S. Lu, X. He, Z. Yang, et al., Nat. Commun. 12 (2021) 4721. doi: 10.1038/s41467-021-25020-9
90. [90]
  R.T. Morris, R.N. Joyrich, R.W. Naumann, et al., Ann. Oncol. 25 (2014) 852–858. doi: 10.1093/annonc/mdu024
91. [91]
  K.N. Moore, A. Angelergues, G.E. Konecny, et al., Engl. J. Med. 389 (2023) 2162–2174. doi: 10.1056/nejmoa2309169
92. [92]
  O. Sartor, J. De Bono, K.N. Chi, et al., N. Engl. J. Med. 385 (2021) 1091–1103. doi: 10.1056/nejmoa2107322
93. [93]
  M. De Wit, Y. Gao, D. Mercieca, et al., EBioMedicine 56 (2020) 102796. doi: 10.1016/j.ebiom.2020.102796
94. [94]
  C.M. Paulos, J.A. Reddy, C.P. Leamon, et al., Mol. Pharmacol. 66 (2004) 1406–1414. doi: 10.1124/mol.104.003723
95. [95]
  C. Zhuang, X. Guan, H. Ma, et al., Eur. J. Med. Chem. 163 (2019) 883–895. doi: 10.1016/j.ejmech.2018.12.035
96. [96]
  M. Srinivasarao, C.V. Galliford, P.S. Low, Nat. Rev. Drug Discov. 14 (2015) 203–219. doi: 10.1038/nrd4519
97. [97]
  F.P. Olatunji, M. Pun, J.W. Herman, et al., Mol. Cancer Ther. 21 (2022) 1701–1709. doi: 10.1158/1535-7163.mct-22-0160
98. [98]
  C. Murga-Zamalloa, S. Webb, J. Reneau, et al., Leuk. Res. Rep. 21 (2024) 100398.
99. [99]
  A. De, P. Roychowdhury, N. Bhuyan, et al., Molecules 28 (2023) 1393. doi: 10.3390/molecules28031393
100. [100]
  M. Ahmadi, C.A. Ritter, T. Von Woedtke, et al., Chem. Sci. 15 (2024) 1966–2006. doi: 10.1039/d3sc05539f
101. [101]
  M. Scaranti, E. Cojocaru, S. Banerjee, et al., Nat. Rev. Clin. Oncol. 17 (2020) 349–359. doi: 10.1038/s41571-020-0339-5
102. [102]
  R. Slack, S. Macdonald, J. Roper, et al., Nat. Rev. Drug Discov. 21 (2022) 60–78. doi: 10.1038/s41573-021-00284-4
103. [103]
  R. Alexanian, A. Haut, A.U. Khan, et al., J. Am. Med. Assoc. 208 (1969) 1680–1685. doi: 10.1001/jama.1969.03160090040009
104. [104]
  G. Bennett, A. Brown, G. Mudd, et al., Mol. Cancer Ther. 19 (2020) 1385–1394. doi: 10.1158/1535-7163.mct-19-1092
105. [105]
  D. Cox, Expert Opin. Drug Discov. 16 (2021) 197–211. doi: 10.1080/17460441.2020.1819234
106. [106]
  X. Pang, X. He, Z. Qiu, et al., Signal Transduct. Target. Ther. 8 (2023) 1. doi: 10.1038/s41392-022-01259-6
107. [107]
  S. Suzuki, W. Argraves, R. Pytela, et al., Proc. Natl. Acad. Sci. U. S. A. 83 (1986) 8614–8618. doi: 10.1073/pnas.83.22.8614
108. [108]
  K. Mishiro, S. Imai, Y. Ematsu, et al., J. Med. Chem. 65 (2022) 16741–16753. doi: 10.1021/acs.jmedchem.2c01586
109. [109]
  M. Sabat, D. Carney, G. Hernandez-Torres, et al., J. Med. Chem. 67 (2024) 10306–10320. doi: 10.1021/acs.jmedchem.4c00743
110. [110]
  X. Montet, M. Funovics, K. Montet-Abou, et al., J. Med. Chem. 49 (2006) 6087–6093. doi: 10.1021/jm060515m
111. [111]
  J. Xiong, J. Chu, W. Fong, et al., J. Am. Chem. Soc. 144 (2022) 10647–10658. doi: 10.1021/jacs.2c04017
112. [112]
  L. Zhang, P. Wang, X. Zhou, et al., J. Am. Chem. Soc. 145 (2023) 14963–14980. doi: 10.1021/jacs.3c04855
113. [113]
  M. Kantlehner, P. Schaffner, D. Finsinger, et al., ChemBioChem 1 (2000) 107–114. doi: 10.1002/1439-7633(20000818)1:2<107::AID-CBIC107>3.0.CO;2-4
114. [114]
  S. Konno, K. Kobayashi, M. Senda, et al., J. Med. Chem. 65 (2022) 2926–2939. doi: 10.1021/acs.jmedchem.1c00665
115. [115]
  Y. Lamb, Drugs 82 (2022) 585–591. doi: 10.1007/s40265-022-01692-5
116. [116]
  J. Paulus, B. Nachtigall, P. Meyer, et al., Chem. Eur. J. 29 (2023) e202203476. doi: 10.1002/chem.202203476
117. [117]
  P. Moharil, Z. Wan, A. Pardeshi, et al., Acta Pharm. Sin. B 12 (2022) 1148–1162. doi: 10.1016/j.apsb.2021.09.024
118. [118]
  M.P. VanBrunt, K. Shanebeck, Z. Caldwell, et al., Bioconjug. Chem. 26 (2015) 2249–2260. doi: 10.1021/acs.bioconjchem.5b00359
119. [119]
  S. Milles, S. Tyagi, N. Banterle, et al., J. Am. Chem. Soc. 134 (2012) 5187–5195. doi: 10.1021/ja210587q
120. [120]
  Z. Wang, H. Li, L. Gou, et al., Acta Pharm. Sin. B 13 (2023) 4025–4059. doi: 10.1016/j.apsb.2023.06.015
121. [121]
  I. Vergote, C.P. Leamon, Ther. Adv. Med. Oncol. 7 (2015) 206–218. doi: 10.1177/1758834015584763
122. [122]
  S. Qin, J. Li, Y. Liu, et al., J. Clin. Oncol. 42 (2024) 3121. doi: 10.1200/jco.2024.42.16_suppl.3121
123. [123]
  B. Gray, L. Kelly, D. Ahrens, et al., Proc. Natl. Acad. Sci. U. S. A. 115 (2018) 4761–4766. doi: 10.1073/pnas.1717705115
124. [124]
  F. Shi, Y. Liu, X. Zhou, et al., Drug Deliv. 29 (2022) 1335–1344. doi: 10.1080/10717544.2022.2069883
125. [125]
  P. Guo, J. Huang, B. Zhu, et al., Sci. Adv. 9 (2023) eabq7866. doi: 10.1126/sciadv.abq7866
126. [126]
  C. Zheng, D. Zhou, W. Li, et al., Cell Death Dis. 14 (2023) 295. doi: 10.1038/s41419-023-05820-1
127. [127]
  X. Wang, A. Shirke, E. Walker, et al., Cancers 13 (2021) 417. doi: 10.3390/cancers13030417
128. [128]
  S. Cazzamalli, A. Dal Corso, D. Neri, J. Control. Release 246 (2017) 39–45. doi: 10.1016/j.jconrel.2016.11.023
129. [129]
  A.S. Rebstock, M. Wiedmann, B. Stelte-Ludwig, et al., Front. Pharmacol. 15 (2024) 1358393. doi: 10.3389/fphar.2024.1358393
130. [130]
  T. Patel, N. Adhikari, S. Amin, et al., New J. Chem. 45 (2021) 5291–5321. doi: 10.1039/d0nj04134c
131. [131]
  S. Schuster, E. Juhasz, G. Halmos, et al., Int. J. Mol. Sci. 23 (2022) 5071. doi: 10.3390/ijms23095071
132. [132]
  P. Berk, J. Goldberg, M. Silverstein, et al., N. Engl. J. Med. 304 (1981) 441– 447. doi: 10.1056/NEJM198102193040801
133. [133]
  N. Greig, E. Daly, D. Sweeney, et al., Cancer Chemother. Pharmacol. 25 (1990) 320–325. doi: 10.1007/BF00686230
134. [134]
  G. Jo, E.J. Kim, H. Hyun, Int. J. Mol. Sci. 23 (2022) 14093. doi: 10.3390/ijms232214093
135. [135]
  Y. Liubomirski, G. Tiram, A. Scomparin, et al., J. Control. Release 367 (2024) 148–157. doi: 10.1016/j.jconrel.2024.01.025
136. [136]
  R. Mukkamala, D. Carlson, N. Miller, et al., J. Nucl. Med. 65 (2024) 1257–1263. doi: 10.2967/jnumed.124.267756
137. [137]
  A. Pal, W. Albusairi, F. Liu, et al., Mol. Pharm. 16 (2019) 3237–3252. doi: 10.1021/acs.molpharmaceut.9b00432
138. [138]
  P. Low, W. Henne, D. Doorneweerd, Acc. Chem. Res. 41 (2008) 120–129. doi: 10.1021/ar7000815
139. [139]
  I.R. Vlahov, C.P. Leamon, Bioconjug. Chem. 23 (2012) 1357–1369. doi: 10.1021/bc2005522
140. [140]
  W. Gao, J. Tian, Y. Shang, Chem. Sci. 11 (2020) 3903–3908. doi: 10.1039/d0sc01060j
141. [141]
  M. Tomczyk, K. Matczak, M. Skonieczna, et al., Bioorganic Chem. 140 (2023) 106782. doi: 10.1016/j.bioorg.2023.106782
142. [142]
  C.Y. Hsu, Y.Y. Chen, C.F. Lo, et al., Cancer Res. 79 (2019) 100897.
143. [143]
  R. Traquete, E. Henderson, S. Picaud, et al., Chem. Commun. 55 (2019) 10128–10131. doi: 10.1039/c9cc05054j
144. [144]
  C.F. Lo, T.Y. Chiu, Y.T. Liu, et al., Pharmaceutics 14 (2022) 1316. doi: 10.3390/pharmaceutics14071316
145. [145]
  Z. Liu, S. Chen, H. Wang, et al., Bioorganic Chem. 129 (2022) 106221. doi: 10.1016/j.bioorg.2022.106221
146. [146]
  Y. Zheng, R. Xu, S. Chen, et al., Biomaterials 290 (2022) 121820. doi: 10.1016/j.biomaterials.2022.121820
147. [147]
  S. Debnath, N. Zhou, M. McLaughlin, et al., Int. J. Mol. Sci. 23 (2022) 1158. doi: 10.3390/ijms23031158
148. [148]
  J.T. Miller, C.N. Vitro, S. Fang, et al., Bioconjug. Chem. 32 (2021) 842–858. doi: 10.1021/acs.bioconjchem.1c00124
149. [149]
  F.P. Olatunji, E.A. Savoy, M. Panteah, et al., Bioconjug. Chem. 32 (2021) 2386–2396. doi: 10.1021/acs.bioconjchem.1c00435
150. [150]
  X. Song, R. Wang, J. Gao, et al., Chin. Chem. Lett. 33 (2022) 1567–1571. doi: 10.1016/j.cclet.2021.08.111
151. [151]
  Y. Yang, Y. Zhang, R. Wang, et al., Chin. Chem. Lett. 33 (2022) 4583–4586. doi: 10.1016/j.cclet.2022.03.040
152. [152]
  Y. Wang, Y. Liu, C. Zhou, et al., Leuk. Lymphoma 61 (2020) 1660–1668. doi: 10.1080/10428194.2020.1728746
153. [153]
  Y. Syed, Drugs 80 (2020) 1019–1025. doi: 10.1007/s40265-020-01337-5
154. [154]
  K. Li, J. Wu, S. Ye, et al., Ann. Oncol. 34 (2023) S991.
155. [155]
  J.A. Reddy, E. Westrick, H.K.R. Santhapuram, et al., Cancer Res. 67 (2007) 6376–6382. doi: 10.1158/0008-5472.CAN-06-3894
156. [156]
  J.A. Reddy, M. Nelson, C. Dircksen, et al., Cancer Res. 77 (2017) 2133. doi: 10.1158/1538-7445.am2017-2133
157. [157]
  E. Fokas, A. Schlenska-Lange, B. Polat, et al., JAMA Oncol. 8 (2022) e215445. doi: 10.1001/jamaoncol.2021.5445
158. [158]
  J. Drago, S. Modi, S. Chandarlapaty, Nat. Rev. Clin. Oncol. 18 (2021) 327–344. doi: 10.1038/s41571-021-00470-8
159. [159]
  C. Dumontet, J. Reichert, P. Senter, et al., Nat. Rev. Drug Discov. 22 (2023) 641–661. doi: 10.1038/s41573-023-00709-2
160. [160]
  Y. Sun, H. Zhang, G. Lu, et al., Chin. Chem. Lett. 34 (2023) 107817. doi: 10.1016/j.cclet.2022.107817
161. [161]
  E. Kim, J. Jeong, J. Lee, et al., Biomolecules 10 (2020) 955. doi: 10.3390/biom10060955
162. [162]
  A. Younes, N. Bartlett, J. Leonard, et al., N. Engl. J. Med. 363 (2010) 1812–1821. doi: 10.1056/NEJMoa1002965
163. [163]
  D. Wei, Y. Mao, H. Wang, et al., Chin. Chem. Lett. 34 (2023) 108091. doi: 10.1016/j.cclet.2022.108091
164. [164]
  J.M. Shillingford, C.P. Leamon, I.R. Vlahov, et al., J. Am. Soc. Nephrol. 23 (2012) 1674–1681. doi: 10.1681/ASN.2012040367
165. [165]
  Y. Lu, K.N. Wollak, V.A. Cross, et al., Clin. Immunol. 150 (2014) 64–77. doi: 10.1016/j.clim.2013.10.010
166. [166]
  C. Li, Pharmacol. Res. 207 (2024) 107341. doi: 10.1016/j.phrs.2024.107341
167. [167]
  A.A. Peterson, D.R. Liu, Nat. Rev. Drug Discov. 22 (2023) 699–722. doi: 10.1038/s41573-023-00713-6
168. [168]
  Q. Nie, S. Zhong, Y. Li, et al., Chin. Chem. Lett. 33 (2022) 2559–2563. doi: 10.1016/j.cclet.2021.09.041
169. [169]
  X. Zeng, H. Xiang, L. Yu, et al., Mach. Intell. 4 (2022) 1004–1016. doi: 10.1038/s42256-022-00557-6
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