Science

Learn about the cutting-edge science behind our DDR therapies

Treating cancer

Targeting DNA damage response (DDR) and replication stress

DDR protects cancer cells from replication stress (RS) by preventing the generation of deadly DNA damage.

Nodus' therapeutic approach aims at exploiting this paradigm by generating RS and inhibiting the DDR through novel targets.

DDR explainer

DNA Damage Response

DNA damage can be categorized into single-strand breaks, double-strand breaks, and replication stress. DNA damage causes changes in the structure of the genetic material and prevents the replication mechanism from functioning and performing properly.

Cancer cells increase the amount of DNA damage, and upregulate repair mechanisms. DDR is a complex signal transduction pathway that recognizes when DNA is damaged and initiates the cellular response to the damage.

One mechanism of DNA damage repair depends on PARP. PARP is a protein that helps damaged cells to repair themselves. PARP enzyme binds tightly to DNA strand breaks and allows repair enzymes to repair the damaged DNA.

DDR explainer

1st wave

PARP inhibitors: First success for synthetic lethality concept. Hugely successful; however, they have issues with resistance and the therapeutic window, which limits their combination options.

DDR explainer

2nd wave

Compounds targeting kinases acting as central nodes of the DDR pathway. These molecules have been tested in several clinical studies with mild success. Only a handful are still active in the clinic, and they have not replicated the synthetic lethality seen with PARP inhibitors.

DDR explainer

3rd wave

This group comprises non-kinase DDR targets, such as helicases, polymerases and nucleases, which regulate more specific mechanisms, thereby increasing their therapeutic window and their potential use in combination with other drugs.

Our inhibitors induce replication stress by exploiting novel modes of action

PARGi

Best-in-class PARG inhibitor
Exploiting DNA repair in tumours with specific vulnerabilities

NOD1

First-in-class DNA replication inhibitor
Novel mode of action to induce replication stress

Learn more about our PARGi programme

Find out why this is a best-in-class PARG inhibitor

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