Traditional Cytotoxic Agents

Traditional Cytotoxic Agents

Catalog Product Name CAS Number Molecular Formula Molecular Weight
BADC-00190 10-Deacetyl-7-xylosyl Paclitaxel 90332-63-1 C50H57NO17 943.98
BADC-00817 Muscotoxin A 1653999-47-3 C58H90N12O16 1211.41 g/mol
BADC-00818 Vipivotide tetraxetan 1702967-37-0 C49H71N9O16 1042.14 g/mol
BADC-00838 17-AEP-GA 75747-23-8 C34H50N4O8 642.78 g/mol
BADC-00839 Mensacarcin 808750-39-2 C21H24O9 420.41
BADC-00858 MC-Val-Cit-PAB-rifabutin 2055900-34-8 C74H101N10O17 1402.65 g/mol
BADC-00859 DGN549-C 2058075-34-4 C60H61N9O12 1100.18 g/mol
BADC-00809 Mytoxin B 105049-15-8 C29H36O9 528.59 g/mol
BADC-00837 Methotrexate disodium 7413-34-5 C20H20N8Na2O5 498.40 g/mol
BADC-00842 Rebeccamycin 93908-02-2 C27H21Cl2N3O7 570.38 g/mol
BADC-00034 Taltobulin 228266-40-8 C27H43N3O4 473.32
BADC-00325 Paclitaxel 33069-62-4 C47H51NO14 853.91
BADC-00037 Methotrexate 59-05-2 C20H22N8O5 454.44
BADC-00035 Taltobulin trifluoroacetate 228266-41-9 C29H44F3N3O6 587.67
BADC-00819 Polyketomycin 200625-47-4 C44H48O18 864.84 g/mol
BADC-00815 Puwainaphycin F 1379577-47-5 C53H87N13O15 1146.34 g/mol
BADC-00816 Aeruginosin 865 1611990-01-2 C41H64N6O14 864.98 g/mol
BADC-00821 β-Amanitin 21150-22-1 C39H53N9O15S 919.95 g/mol
BADC-00840 Hygrolidin 83329-73-1 C38H58O11 690.86 g/mol
BADC-00808 Sandramycin 100940-65-6 C60H76N12O16 1221.32 g/mol

As a representative of the development direction of the new generation of antibody technology, antibody drug conjugates (ADCs) have high specificity of antibodies and high toxicity of cytotoxic drugs to tumors. Cytotoxic Agents play an anti-tumor role in ADCs, which can affect the expected efficacy of target tumors. Its chemical structure, coupling mode and coupling number also affect the biological activity of the antibody. In theory, cytotoxic substances such as chemotherapeutic drugs, toxins and radionuclides that have great killing effects on tumor cells can be used as cytotoxic molecules of ADCs.

Chemical characteristics and mechanism of action

The choice of cytotoxins is crucial for ADCs. The cytotoxin used for coupling must have clear mechanism of action, small molecular weight, high activity, and no immunogenicity, and they can still retain anti-tumor activity after chemically coupled to the antibody. At present, the mechanism of anticancer drugs used in clinic is mostly to interfere with or block the proliferation of cells.  According to the mechanism, it can be roughly divided into four categories.

  • Inhibition of DNA synthesis. The main structural characteristics of this anticancer drugs are as follows: containing a pyrimidine or heterocyclic compound similar to pyrimidine, and a glucose analogue with five-membered ring. It interferes with DNA synthesis by blocking the synthesis and exchange of deoxypurine nucleosides or deoxypyrimidine nucleosides. Such as, 5-Fluorouracil, which mainly exerts anticancer effects through antimetabolic effects.
  • Destruction of DNA structure or DNA synthesis. Anticancer drugs that directly destroy DNA structures or synthesize DNA are mostly alkylating agents and anticancer antibiotics. The structure and function of DNA are destroyed by cross-linking with DNA through alkylation. For example, nitrogen mustard alkylating agent betamerphalan mainly exerts anticancer effect through alkylation.
  • Inhibition of protein synthesis. Most of these drugs contain antifolate whose core is a pyrrole or pyrazine pyrimidine group, which affect the normal replication process of proteins by destroying the activity of intracellular folate reductase, thus inhibiting the growth of tumors.  Such as, pemetrexed disodium and methotrexate.
  • Inhibition of cell mitosis. These anticancer drugs are mainly characterized by multi-hydroxyl and multi-thick ring structural. Alkaloids derived from plants account for the majority of active ingredients. Such as, vincristine and vindesine.

Application

The selection of cytotoxic is very wide. In principle, compounds with high enough inhibitory activity against tumor cells can be used as coupling drugs. At present, the most cytotoxic used in ADCs are Auristatins, Maytansine and Calicheamicins. Majority of clinical research involving ADCs projects use tubulin inhibitors, and both subtoxoids have approved products on the market (Adcetris uses oristatin MMAE and Kadcyla uses maytansinoid DM1). Among them, Auristatin is dominating the market, accounting for more than 50% of ADC drugs under investigation.

References

  1. Hamilton, G.S. Antibody-drug conjugates for cancer therapy: The technological and regulatory challenges of developing drug-biologic hybrids. Biologicals, 2015, 43: 318-332.
  2. Dan, N.; et al. Antibody-Drug Conjugates for Cancer Therapy: Chemistry to Clinical Implications. Pharmaceuticals, 2018, 11: 32.
* Only for research. Not suitable for any diagnostic or therapeutic use.

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