4.5 Review

CDC7 kinase inhibitors: a survey of recent patent literature (2017-2022)

Journal

EXPERT OPINION ON THERAPEUTIC PATENTS
Volume 33, Issue 7-8, Pages 493-501

Publisher

TAYLOR & FRANCIS LTD
DOI: 10.1080/13543776.2023.2262138

Keywords

ALS; cancer; CDC7; DNA damage response; DNA replication; kinase inhibitors; mitotic catastrophe; small molecule inhibitors

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Although CDC7 has been recognized as a potential target for cancer treatments, there is a lack of chemical scaffolds as CDC7 inhibitors. The failure of clinical trials may be due to dose-limiting toxicities and the importance of patient stratification.
IntroductionCDC7 is a serine/threonine kinase which plays an important role in DNA replication. Inhibition of CDC7 in cancer cells causes lethal S phase or M phase progression, whereas inhibition of CDC7 in normal cells does not cause cell death and only leads to cell cycle arrest at the DNA replication checkpoint. Therefore, CDC7 has been recognized as a potential target for novel therapeutic interventions in cancers.Areas coveredPatent literature claiming novel small molecule compounds inhibiting CDC7 disclosed from 2017 to 2022.Expert opinionDespite the indisputable positive impact of CDC7 as a drug target, there have been reported only a handful of chemical scaffolds as CDC7 inhibitors. Several CDC7 inhibitors have been progressed into clinical trials for cancer treatments, but they did not result in satisfactory efficacies in those trials. One possible reason for the failure might be due to the dose-limiting toxicities, and some of the observed toxicities were thought to be not related to CDC7 inhibition, suggesting it should be important to identify novel chemical scaffolds to eliminate unwanted toxicities. Another important factor is the patient stratification that would enable greater response, and the identification of such predictive biomarkers should be the key to success for the development of CDC7 inhibitors.

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