Vinorelbine

Creative Biolabs is a well-recognized leader in providing antibody-drug conjugates (ADCs) development services. With our extensive experience in full synthetic chemistry, bio-conjugation, and with the advanced “DrugLnk” platform, we are dedicated to provide our clients with highly customized ADC production using vinorelbine or vinorelbine derivatives as payloads.

Vinorelbine, a semi-synthetic vinca alkaloid, is derived from the coupling of catharantine and vindoline. Vinca alkaloids are a group of anti-microtubule and anti-mitotic alkaloid agents initially isolated from the periwinkle plant Catharanthus roseus and later from several other vinca plants. Unlike the natural compounds containing a nine-member catharanine ring, vinorelbine has an eight-member ring structure. Vinorelbine induces cytotoxicity through restraining microtubule assembly similar to other alkaloids. Interestingly, vinorelbine has been shown to exhibit a higher tendency towards the inhibition of mitosis in other somatic cells comparing to that in neural axons, resulting in a decreased neurotoxicity comparing to other alkaloids. Currently, vinorelbine is been exploited as a powerful chemotherapeutic agent in the treatment of various types of cancer, including breast cancer and non-small cell lung cancer.

Structure of vinorelbine and another vinca alkaloid: vinflunine (Biochem Pharmacol, 2002).

Vinorelbine mode of action (MOA)

Vinorelbine functions by binding to the microtubules inside the cells and inhibiting mitosis at metaphase through the interaction with tubulin. Microtubule is a pivotal component in the separation of the cell’s DNA during cell division. Unfortunately, the toxicity of vinorelbine is non-selective and both tumor and healthy cells will be affected upon exposure. Interestingly, non-oncogenic cells show better recovery from vinorelbine damage than tumor cells, presumably due to the elevated mitotic activities in tumor cells. In terms of system clearance, vinorelbine is cleared from circulation through the biliary system in liver, while some of its by-products are cleared by kidney.

Structure of vinorelbine and a schematic diagram of the MOA of vinca alkaloids, including vinorelbine, and other microtubule-inhibitory agents. Vinorelbine inhibits both growth and shortening of microtubules (Clin Cancer Res., 2011).

Vinorelbine-based ADCs

ADCs are designed to utilize the specificity of monoclonal antibodies (mAbs) to transport strong cytotoxic drugs selectively to antigen-expressing tumor cells. As a potent anti-microtubule and anti-mitotic agents, vinorelbine has been developed as a chemotherapy medication used to treat cancers. The application of vinorelbine is limited due to its high cytotoxicity, however, this very reason makes vinorelbine an appropriate candidate to be exploited as an ADC payload. Creative Biolabs is confident in the preparation of ADCs using vinorelbine with optimal conjugate strategies and linkers.

With our well-established “DrugLnk” organic synthesis platform, the experienced scientists here at Creative Biolabs is dedicated to help you develop vinorelbine -linker complexes using readily available or customized linkers for ADC preparation in a timely and cost-effective manner. Our customarily tailored services and high quality products will contribute greatly to the success of your projects.

Creative Biolabs also provides other various services regarding ADC development. Please feel free to contact us for more information and a detailed quote.

References:

1. Casanova, M.; et al. Vinorelbine in previously treated advanced childhood sarcomas. Cancer. 2002, 94(12): 3263-3268.
2. Kavallaris M.; et al. Microtubules and resistance to tubulin-binding agent. Nature Reviews Cancer. 2010, 10(3): 194-204.
3. Jain, S.; Vahdat, L.T. Eribulin mesylate. Clin Cancer Res. 2011, 17(21): 6615-6622.
4. Fabre, C.; et al. Differential binding to the α/β-tubulin dimer of vinorelbine and vinflunine revealed by nuclear magnetic resonance analyses. Biochem Pharmacol. 2002, 64(4): 733-740.