Traditional Cytotoxic Agents

Traditional Cytotoxic Agents

Catalog Product Name CAS Number
BADC-00837 Methotrexate disodium 7413-34-5
Methotrexate (Amethopterin) disodium, an antimetabolite and antifolate agent, inhibits the dihydrofolate reductase, thereby preventing the conversion of folic acid into tetrahydrofolate, and inhibitin... Inquiry
BADC-00184 Tubulysin A 205304-86-5
Tubulysin A is a novel antibiotic, which exhibits anti-microtubule, anti-mitotic, apoptosis inducer, anticancer, anti-angiogenic, and antiproliferative activity. Tubulysins show very high cytotoxic ac... Inquiry
BADC-00325 Paclitaxel 33069-62-4
Paclitaxel is a compound with anti-tumor activity extracted from the Pacific yew tree Taxus brevifolia. Paclitaxel is a microtubule polymer stabilizer with IC50 of 0.1 pM in human endothelial cells. Inquiry
BADC-00842 Rebeccamycin 93908-02-2
Rebeccamycin, an antitumor antibiotic, inhibits DNA topoisomerase I. Rebeccamycin appears to exert its primary antineoplastic effect by poisoning topoisomerase I and has negligible effect on protein k... Inquiry
BADC-00190 10-Deacetyl-7-xylosyl Paclitaxel 90332-63-1
10-Deacetyl-7-xylosyl paclitaxel is a Paclitaxel derivative with improved pharmacological features and higher water solubility. Inquiry
BADC-00840 Hygrolidin 83329-73-1
Hygrolidin is a 16-membered macrolide antibiotic produced by Streptomyces hygroscopicus D-1166. Hygrolidin has anti-fungus activity against Valsa ceratosperma. Hygrolidin induces p21 expression and ab... Inquiry
BADC-00831 Telomestatin 265114-54-3
Telomestatin is a very potent telomerase inhibitor and can be isolated from Streptomyces anulatus 3533-SV4. Telomestatin selectively facilitates the formation of intramolecular G-quadruplexes, in part... Inquiry
BADC-00869 AcLysValCit-PABC-DMAE-SW-163D 2411007-69-5
AcLysValCit-PABC-DMAE-SW-163D is a drug-linker conjugates for ADC which consists of a natural bis-intercalator, SW-163D, conjugated via an AcLysValCitPABC-DMAE linker. Inquiry
BADC-00823 ε-Amanitin 21705-02-2
ε-Amanitin, a cyclic peptide isolated from a variety of mushroom species, potently binds to and inhibits the activity of RNA polymerase II. Inquiry
BADC-00860 Mal-PEG2-VCP-Eribulin 2130869-18-8
Mal-PEG2-VCP-Eribulin consists the ADCs linker (Mal-PEG2-VCP) and Eribulin. Eribulin is a mechanistically unique microtubule inhibitor for cancer. Mal-PEG2-VCP-Eribulin is an Eribulin-based drug for a... Inquiry
BADC-00821 β-Amanitin 21150-22-1
β-Amanitin is a cyclic peptide toxin in the poisonous Amanita phalloides mushroom. β-Amanitin inhibits eukaryotic RNA polymerase II and III. β-Amanitin inhibits protein synthesis. β-Amanitin can be us... Inquiry
BADC-00859 DGN549-C 2058075-34-4
DGN549-C consists a cleavable ADC linker valine-alanine (va) and PBD dimer. DGN549 is a novel DNA-alkylating cytotoxic payload and can be used in the synthesis of antibody-drug conjugates (ADCs). Inquiry
BADC-00858 MC-Val-Cit-PAB-rifabutin 2055900-34-8
MC-Val-Cit-PAB-rifabutin is a drug-linker conjugate for ADC with potent antitumor activity by using rifabutin (an DNA-dependent RNA polymerase inhibitor), linked via the ADC linker MC-Val-Cit-PAB. Inquiry
BADC-00857 MC-Val-Cit-PAB-vinblastine 2055896-92-7
MC-Val-Cit-PAB-vinblastine is a drug-linker conjugate for ADC with potent antitumor activity by using vinblastine (an microtubule protein inhibitor), linked via the ADC linker MC-Val-Cit-PAB. Inquiry
BADC-00818 Vipivotide tetraxetan 1702967-37-0
Vipivotide tetraxetan is a high potent inhibitor of prostate-specific membrane antigen (PSMA)(Ki of 0.37 nM). Inquiry
BADC-00817 Muscotoxin A 1653999-47-3
Muscotoxin A is an ADC cytotoxin. Muscotoxin A is a cytotoxic lipopeptide that permeabilizes mammalian cell membranes and induces necrotic cell death. Inquiry
BADC-00853 MC-VC-PABC-DNA31 1639352-03-6
MC-VC-PABC-DNA31 is a drug-linker conjugate for ADC with potent antitumor activity by using DNA31 (a potent RNA polymerase inhibitor), linked via the ADC linker MC-VC-PABC. Inquiry
BADC-00815 Puwainaphycin F 1379577-47-5
Puwainaphycin F, a cyanobacterial cyclic lipopeptide, is a moderate cytotoxin isolated from the soil cyanobacterium Cylindrospermum alatosporum C24/89. Puwainaphycin F causes necrotic cell death to ma... Inquiry
BADC-00808 Sandramycin 100940-65-6
Sandramycin ia a cyclic depsipeptide antibiotic isolated from cultured broth of a Nocardioides sp. Sandramycin is also a DNA intercalator that potently binds DNA and is an ADC cytotoxin. Sandramycin i... Inquiry
BADC-00845 Isofistularin-3
Isofistularin-3 is a direct, DNA-competitive DNMT1 inhibitor, with an IC50 of 13.5 μM. Isofistularin-3, as a DNA demethylating agent, induces cell cycle arrest and sensitization to TRAIL in cancer cel... Inquiry

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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