Creative Biolabs has developed an advanced “DrugLnk” platform for antibody-drug conjugates (ADCs) development. With rich experience in payload drug chemistry, we offer highly customized services for targeted antibody therapeutics development and ADC production using topotecan and its analogues as payloads.

Topotecan, a water-soluble camptothecin analog, exists at physiological pH as an equilibrium between the lactone form and the acarboxylate form. Topotecan was first isolated from the oriental yew tree, Camptotheca accuminata,and was approved in 1996 for the treatment of recrudescent ovarian cancer. It is a strong topoisomerase I poison and induces cytotoxicity during the process of DNA replication by stabilizing the molecular complex formed between DNA and topoisomerase I. Topotecan has also been reported to inhibit the religation of enzyme mediated single-strand DNA breaks. It shows an improved anti-neoplastic activity when administered daily for prolonged periods of time and it is now applicable in the treatments of various tumors, including cervical cancer, ovarian cancer, and small cell lung cancer (SCLC).

Topotecan Chemical structures of the lactone form (left) and carboxylate form (right) of topotecan (J Pharmacol Exp Ther, 2007)

Topotecan Mode of Action (MOA)

Topotecan acts as a DNA replication inhibitor by hindering the function of topoisomerase I. With the progression of DNA replication in dividing cells, topoisomerase I functions by adhering to super-coiled DNA and inducing single-stranded breakages, thereby enabling the relief of torsional stresses among double-stranded DNA (dsDNA) at the replication fork along the progression of the replication complex. Topotecan binds to the dsDNA-topoisomerase complex and intervenes the religation of DNA strand breaks, resulting in an interruption of DNA replication and subsequently, cell death. Topotecan’s MOA is non-selective and it targets the replication machinery in both healthy and tumor cells. Hence, to fully exploit its therapeutic potential in cancer treatment, novel strategies are urgently needed to achieve targeted topotecan delivery to tumors.

Topotecan Structure of topoisomerase I–DNA complex without (A) and with (B) bound topotecan (PNAS, 2002). Topoisomerase I inhibition causes the expression of synaptic adhesion molecules (C and D) that induces apoptosis (PNAS, 2014).

Topotecan-based ADCs

ADC technology uses monoclonal antibodies to deliver highly potent pharmaceutical agents to targeted cancer cells. This approach enables selective toxicity against antigen–expressing tumor cells with reduced collateral damage to healthy tissues, increasing the efficacy and safety profile of cytotoxins. As a highly potent topoisomerase I inhibitor, topotecan has exhibited beneficial effects on a variety of tumor cells. Therefore, topotecan may be a promising payload candidate for ADC development. With our rich experience in full chemical synthesis and bio-conjugation, scientists at Creative Biolabs are confident in preparing customized topotecan-based ADCs.

With our well-established “DrugLnk” organic synthesis platform, the experienced scientists here at Creative Biolabs are dedicated to help our clients develop topotecan-linker complexes using readily available or customized linkers and couple topotecan with various antibodies via bio-conjugation 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.


  1. Matsumoto, S.; et al. Involvement of rat and human organic anion transporter 3 in the renal tubular secretion of topotecan [(S)-9-dimethylaminomethyl-10- hydroxy-camptothecin hydrochloride]. J Pharmacol Exp Ther. 2007, 322(3): 1246-1252.
  2. Staker, B.L.; et al. The mechanism of topoisomerase I poisoning by a camptothecin analog. PNAS. 2002, 99(24): 15387-15392.
  3. Mabb, A.M.; et al. Topoisomerase 1 inhibition reversibly impairs synaptic function. PNAS. 2014, 111(48): 17290-17295.

For Research Use Only. NOT FOR CLINICAL USE.

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