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Signaling Pathways

The antibody-drug conjugate (ADC), a humanized or human monoclonal antibody conjugated with highly cytotoxic small molecules (payloads) through chemical linkers, is a novel therapeutic format and has great potential to make a paradigm shift in cancer chemotherapy. The three components of the ADC together give rise to a powerful oncolytic agent capable of delivering normally intolerable cytotoxins directly to cancer cells, which then internalize and release the cell-destroying drugs. At present, two ADCs, Adcetris and Kadcyla, have received regulatory approval with >40 others in clinical development.

ADCs are administered intravenously in order to prevent the mAb from being destroyed by gastric acids and proteolytic enzymes. The mAb component of the ADC enables it to circulate in the bloodstream until it finds and binds to tumor-specific cell surface antigens present on target cancer cells. Linker chemistry is an important determinant of the safety, specificity, potency and activity of ADCs. Linkers are designed to be stable in the blood stream (to conform to the increased circulation time of mAbs) and labile at the cancer site to allow rapid release of the cytotoxic drug. First generation ADCs made use of early cytotoxins such as the anthracycline, doxorubicin or the anti-metabolite/antifolate agent, methotrexate. Current cytotoxins have far greater potency and can be divided into three main groups: auristatins, maytansines and calicheamicins.

The development of site-specific conjugation methodologies for constructing homogeneous ADCs is an especially promising path to improving ADC design, which will open the way for novel cancer therapeutics.


[1] Tsuchikama K, et al. Protein Cell. 2016 Oct 14. DOI:10.1007/s13238-016-0323-0.

[2] Peters C, et al. Biosci Rep. 2015 Jun 12;35(4). pii: e00225. doi: 10.1042/BSR20150089.

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  2. GC45195 α,β-Methyleneadenosine 5’-triphosphate (sodium salt) α,β-Methyleneadenosine 5'-triphosphate (αβ-methylene ATP) is a phosphonic analog of ATP that is characterized by the replacement of the bridging oxygen atom between the α- and β-phosphate groups with methylene.
  3. GC40262 α-Humulene α-Humulene is a sesquiterpene that has been found in C.
  4. GC40302 α-hydroxy Tamoxifen Tamoxifen is a selective estrogen receptor (ER) modulator that is widely used in the therapeutic and chemopreventive treatment of breast cancer.
  5. GC45213 α-NETA Choline acetyltransferase (ChAT) mediates the synthesis of the neurotransmitter acetylcholine from acetyl-CoA and choline.
  6. GC38287 α-Pyridone
  7. GC37979 α-Terpineol
  8. GC37980 α-Tocopherol phosphate
  9. GC45224 α-Truxillic Acid α-Truxillic acid can be formed by the dimerization of two molecules of α-trans-cinnamic acid.
  10. GC40753 α-Zearalanol α-Zearalanol is an active metabolite formed by reduction of α-zearalenol, an estrogen receptor antagonist.
  11. GC37975 α2β1 Integrin Ligand Peptide
  12. GC38873 α2β1 Integrin Ligand Peptide TFA
  13. GC37984 β-Amyloid (1-42), rat
  14. GC37986 β-Amyloid 1-17
  15. GC37987 β-Amyloid 1-20
  16. GC37993 β-Amyloid 1-9
  17. GC37985 β-Amyloid 11-22
  18. GC37988 β-Amyloid 12-20
  19. GC37992 β-Amyloid 18-28
  20. GC37994 β-Amyloid 22-40
  21. GC37995 β-Amyloid 33-40

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