DC1, an analogue of the minor groove-binding DNA alkylator CC-1065, is an ADC cytotoxic for the targeted treatment of cancer.
Structure of 169901-27-3
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NCT Number | Condition Or Disease | Phase | Start Date | Sponsor | Status |
---|---|---|---|---|---|
NCT04625595 | Type1 Diabetes | Phase 1 | 2021-08-25 | Immunomolecular Therapeutics, Inc. | Completed |
NCT02787915 | Renal Cell Carcinoma | Phase 1 | 2016-06-02 | Xuzhou Medical University | Unknown Verified May 2016 by Junnian Zheng, Xuzhou Medical University. Recruitment status was Not yet recruiting |
NCT02336984 | Breast Cancer | Phase 1, Phase 2 | 2021-01-11 | H. Lee Moffitt Cancer Center and Research Institute | Withdrawn (PI left Abramson Cancer Center and study never opened at Moffitt Cancer Center.) |
NCT03630809 | Breast Cancer | Phase 2 | 2021-11-22 | H. Lee Moffitt Cancer Center and Research Institute | Suspended (Suspended for protocol revisions) |
NCT03474536 | Lung Transplantation | 2020-04-29 | University Hospital, Bordeaux | Completed |
DC1 is a synthetic cytotoxic compound and a potent ADC cytotoxin utilized as an ADC payload in antibody-drug conjugates. Its cytotoxic mechanism involves DNA intercalation and topoisomerase inhibition, leading to disruption of DNA replication, cell cycle arrest, and apoptosis in proliferating tumor cells. The chemical structure of DC1 allows stable conjugation to monoclonal antibodies via cleavable or non-cleavable linker chemistries, enabling targeted intracellular delivery in ADC applications while maintaining systemic stability.
In antibody-drug conjugates, DC1 is covalently linked to antibodies using linker strategies that preserve payload stability in circulation and enable selective intracellular release. The ADC remains inactive during systemic circulation, minimizing off-target toxicity. Following receptor-mediated internalization into antigen-expressing tumor cells, enzymatic or chemical cleavage liberates DC1, which binds DNA and inhibits topoisomerase activity, leading to replication arrest and apoptosis. This targeted delivery ensures that cytotoxic effects are confined to tumor cells, supporting precise tumor-targeted therapy in ADC constructs.
Applications of DC1 include incorporation into ADCs targeting both hematologic malignancies and solid tumors with defined antigen expression. Its chemical compatibility with a variety of linker chemistries allows optimization of conjugation efficiency, intracellular release kinetics, and pharmacokinetic profiles. Preclinical evaluations demonstrate reproducible cytotoxicity in target-expressing tumor cells. DC1 supports the development of ADCs with defined DNA-damaging mechanisms, providing mechanistically precise apoptosis induction and tumor cell elimination, facilitating rational design of antibody-drug conjugates for targeted cancer therapy.
What is DC1?
DC1 is a potent cytotoxic compound utilized in antibody-drug conjugates for targeted cancer therapy. Its mechanism involves microtubule inhibition, leading to cell cycle arrest and apoptosis, making it a valuable payload for ADC design.
2/11/2021
Could you kindly advise how DC1 is integrated into ADCs?
DC1 is conjugated to antibodies via cleavable or non-cleavable linkers, enabling selective delivery to antigen-expressing tumor cells. This targeted approach enhances therapeutic efficacy while reducing off-target toxicity.
27/5/2019
We are interested in which linker chemistries are compatible with DC1.
DC1 can be linked using peptide-based, disulfide, or other bioconjugation linkers. The choice of linker determines stability, release kinetics, and ADC pharmacokinetics, which are critical for preclinical and clinical development.
28/3/2020
Dear BOC Sciences, could you please let me know if you provide DC1 ADC customization?
BOC Sciences provides full DC1 ADC services including payload conjugation, linker optimization, and analytical support. Our platform allows tailored ADC design to meet specific research requirements and enhance drug development efficiency.
25/6/2022
Dear BOC Sciences, what precautions should be taken when handling DC1?
DC1 is a highly potent cytotoxin, necessitating rigorous safety measures such as PPE, containment, and adherence to laboratory protocols to minimize risk of exposure during handling and conjugation procedures.
30/4/2019
— Dr. James Parker, Senior Scientist (USA)
DC1 supplied by BOC Sciences met our expectations for purity and stability, enabling efficient ADC assays.
28/3/2020
— Dr. Jonathan Miles, Senior Scientist (USA)
DC1 delivered by BOC Sciences showed excellent stability and high purity, which greatly supported our conjugation experiments.
30/4/2019
— Ms. Anika Hoffmann, R&D Manager (Germany)
The DC1 batch arrived on schedule with comprehensive QC reports, enabling seamless integration into our ADC workflow.
25/6/2022
— Dr. Oliver Bennett, Biopharmaceutical Researcher (UK)
We observed consistent performance in all assays using DC1, highlighting the quality and reproducibility from BOC Sciences.
2/11/2021
— Mr. Pierre Dubois, Medicinal Chemist (France)
Technical support during DC1 procurement was prompt and knowledgeable, helping us optimize our ADC conjugation process.
— Dr. Emma Johansson, Laboratory Head (Sweden)
Working with BOC Sciences for DC1 supply has been smooth, with reliable documentation and reproducible batch quality.
27/5/2019
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