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CDC7 Inhibitors
Cancer Research Horizons
Small molecule
Oncology
Pre-Clinical
Highlights
Cell division cycle 7-related kinase (CDC7) is a nuclear serine/threonine kinase that is of critical importance to the regulation of normal cell cycle progression during the G1 to S transition. CDC7 is a highly explored cancer target owing to its potential to selectively induce apoptosis in cancer cells. CDC7 overexpression is correlated with poor clinical outcomes in several cancers, and it has been identified in 50% of human cancer cell lines tested, correlated strongly with TP53 overexpression (Bonte et al., 2008, Neoplasia). However, a clear disease position for inhibiting CDC7 is yet to be robustly identified.
We present lead-optimised pre-candidate CDC7 inhibitors developed in-house at the Cancer Research Horizons Therapeutic Innovations laboratories. Our molecules deliver potent enzyme inhibition (4nM IC50). Lead compound CRT’2199 (backup molecules are available) has demonstrated potent, dose-dependent tumour inhibition in xenograft models of DLBCL and renal cancers, with favourable tolerability and a low human predicted efficacious dose. Further data is required to identify the target patient population for our CDC7 inhibitors prior to clinical entry.
CRUK-funded research identified the crystal structure of the CDC7 protein, and via a unique crystallography platform, prioritised small molecule inhibitors from unique chemical lineages. Our CDC7 inhibitors are chemically distinct, with chemical cores of interest covered by composition of matter patent claims (patent families WO 2018/055402 and WO 2018/087527). Our CDC7 patent portfolios provide wide territorial coverage, and both families are granted in USA, Great Britain, Germany, Spain, France and Italy.
Emma L. Carswell, Mark David Charles
US 10919896 B2 (2021.02.16)
Patent Family: PCT, US, EP, JP, CN, CA, AU
US 11020396 B2 (2021.06.01)
Patent Family: PCT, US, EP, JP, CN, CA, AU
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