2. Academic Validation
  3. Small molecule-drug conjugates: A novel strategy for cancer-targeted treatment

Small molecule-drug conjugates: A novel strategy for cancer-targeted treatment

  • Eur J Med Chem. 2019 Feb 1;163:883-895. doi: 10.1016/j.ejmech.2018.12.035.
Chunlin Zhuang 1,  Xianghong Guan 2,  Hao Ma 3,  Hui Cong 4,  Wannian Zhang 3,  Zhenyuan Miao 5
Affiliations

Affiliations

  • 1 School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai, 200433, China; School of Pharmacy, Ningxia Medical University, 1160 Shengli Street, Yinchuan, 750004, China. Electronic address: [email protected].
  • 2 Department of Medicinal Chemistry, Institute for Therapeutics Discovery and Development, University of Minnesota, 717 Delaware Street SE, Minneapolis, MN, 55414, USA.
  • 3 School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai, 200433, China; School of Pharmacy, Ningxia Medical University, 1160 Shengli Street, Yinchuan, 750004, China.
  • 4 School of Pharmacy, Ningxia Medical University, 1160 Shengli Street, Yinchuan, 750004, China.
  • 5 School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai, 200433, China. Electronic address: [email protected].
PMID: 30580240 DOI: 10.1016/j.ejmech.2018.12.035
Abstract

Targeted therapy has become an effective strategy of precision medicine for improving Cancer treatment. Selectivity improvement is always popular in modern oncology because of decreased side effects in conventional Cancer chemotherapy. The use of antibody-drug conjugates (ADC), a robust strategy for targeted therapy, applies Antibodies to selectively deliver a potent cytotoxic compound to tumor cells and thus improve the therapeutic efficacy of the chemotherapeutic agents. Three ADC products (trastuzumab emtansine, brentuximab vedotin and inotuzumab ozogamicin) are already on the market, and several compounds are in clinical trials. Compared with ADCs, small molecule-drug conjugates (SMDCs) provide a new, less established perspective for targeted delivery. Nevertheless, SMDCs have several strengths: they have 1) a non-immunogenic nature, 2) much more manageable synthesis, 3) lower molecular weights, which confer a high potential for good cell penetration in solid tumors. SMDCs might therefore be a promising alternative with similar efficacy to ADCs. In this article, we highlight the medicinal chemistry aspects of SMDC design. SMDC targeting ligands, linkers and small-molecule payloads will be discussed. Successful cases of SMDCs used as therapeutic agents and other applications of SMDC will also be included.

Keywords

Cancer-targeted; Drug design; Small molecule-drug conjugates; Strategy.

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