We continue our series in the Biologics campaign – now it is devoted to Cell division cycle 7 (CDC7) serine-threonine kinase.
Cell division cycle 7-related protein kinase is a serine-threonine enzyme that in humans is encoded by the CDC7 gene and participates in multiple cellular processes, like DNA replication, chromosomal segregation, S-phase cell cycle progression, and DNA damage checkpoint. CDC7 is often highly expressed in several types of neoplasm, therefore it has been linked with cancer growth and poor clinical results. Functional studies in different cancer models show that CDC7 may be an attractive target for antineoplastic treatment, so several CDC7 inhibitors are in progress.
You can find more information about the implication of this target in cancer cell biology here.
Optimizing a series of furanone analogs with a focus on ADME properties leads to a suitable CDC7 inhibitor for clinical development. Replacing the aromatic moiety with various aliphatic groups guided the new potent candidate with excellent kinase selectivity and favorable oral bioavailability in multiple species. The drug candidate AS-0141 shows robust in vivo antitumor efficacy in a colorectal cancer xenograft model.
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