Oncology
CV6-168 is a potential first-in-class, oral small molecule inhibitor of dUTPase, developed to work in combination with standard chemotherapies that block DNA synthesis in cancer cells, known as thymidylate synthase inhibitors such as 5-FU and pemetrexed.
TS inhibitors work by depleting thymine, one of the four essential DNA building blocks A, T, C, and G. Without thymine (T), cancer cells cannot replicate their DNA properly, disrupting DNA replication. However, many cancers develop resistance, either by bypassing the blockade or evolving over time, limiting the effectiveness of these cornerstone therapies.
CV6-168
CV6-168 is designed to address this limitation through a distinct mechanistic approach to TS inhibition. Rather than solely depleting thymine availability, CV6-168 blocks the enzyme dUTPase, leading to a buildup of uracil, a base not normally found in DNA. When TS inhibitors deplete thymine, uracil may be incorporated into DNA during replication. Preclinical studies indicate that this process triggers DNA repair responses associated with genomic stress and innate immune activation.
This approach is designed to exploit vulnerabilities associated with highly proliferative cancer cells, which may exhibit impaired genomic maintenance mechanisms, supporting investigation of differentiated anti-tumor activity.
CV6-168 is currently in a Phase 1a clinical trial in Northern Ireland and Great Britain. Learn more about the Phase 1a trial here: ISRCTN registry.
