CC-1065 Analogs

Creative Biolabs has developed a series of new and highly cytotoxic CC-1065 analogues for ADC generation. CC-1065 analogs are a class of alkylating agents that are highly suitable for targeted tumor therapies.

Figure: Structure of CC-1065 (J Antibiot. 1981)

CC-1065 is a natural anti-tumor agent with a unique structure produced by Streptomyces zelensis. The Streptomyces zelensis producing CC-1065 was selected from screening for soil cultures producing agents displaying both cytotoxic activity against L1210 cells in culture and in vivo activity against P388 leukemia. A molecule model of CC-1065 displayed a remarkable curvature, shape and charge density peculiarly efficient for nestling in the grooves of the DNA double helix. CC-1065 can inhibit 90% cell growth in the concentration of 0.05ng/ml, the cytotoxicity of which is 400 times more than that of adriamycin. The mechanisms of action of CC-1065 include that it inhibits DNA polymerase α and thymidine kinase activities to suppress DNA synthesis. Besides these MOAs, CC-1065 can also raise DNA thermal melting temperature and inhibit its ethidium-induced unwinding, stabilizing the DNA helix. As one of the most cytotoxic agents known, CC-1065 is intensively studied in antitumor therapy. Compared to CC-1065, its analogues, such as adozelesin, carzelesin and bis-indolyl-(seco)-CBl3 derivatives, have high activity but lack delayed systemic toxicity. They are highly cytotoxic to a broad spectrum of tumor cells. These drugs are DNA alkylators and can be used as therapic agents because they can bind tightly to the minor groove of DNA and then react covalently with adenine base. There are several ADCs based on CC-1065 analogues that have been developed, and these ADCs have been proven to be extremely potent and antigen selective in killing tumor cells.

Categories of ADC payloads that Creative Biolabs provides:

1. Toxins targeting tubulin filaments: Maytansinoids, Auristatins, Taxoids, etc.
2. Toxins targeting DNA: Calicheamicins, CC-1065 analogs, Duocarmycins, etc.
3. Toxins targeting RNA: Amatoxins, etc.
4. Nanocarriers 
5. Protein toxins
6. Enzymes

References

1. Ravi V. J. Chari, et al. Enhancement of the selectivity and antitumor efficacy of a CC-1065 analogue through immunoconjugate formation. Cancer Res. 1995 Sep 15; 55(18):4079-84.
2. David G. Martin, et al. CC-1065 (NSC 298223), a potent new antitumor agent improved production and isolation, characterization and antitumor activity. J Antibiot (Tokyo). 1981 Sep; 34(9):1119-25.
3. L. H. LI, et al. CC-1065 (NSC 298223), a Novel Antitumor Agent That Interacts Strongly with Double-stranded DNA. Cancer Res. 1982 Mar; 42(3):999-1004.

For research use only. Not intended for any clinical use.