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

ABSTRACTIntroduction CDC7 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, 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 covered Patent literatures claiming novel small molecule compounds inhibiting CDC7 disclosed from 2017 to 2022.Expert opinion Despite 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.KEYWORDS: ALScancerCDC7DNA damage responseDNA replicationkinase inhibitorsmitotic catastrophesmall molecule inhibitorsDisclaimerAs a service to authors and researchers we are providing this version of an accepted manuscript (AM). Copyediting, typesetting, and review of the resulting proofs will be undertaken on this manuscript before final publication of the Version of Record (VoR). During production and pre-press, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal relate to these versions also. Article highlightsCDC7 inhibitors may become a new generation of cancer drug with a unique mechanism of action.Only a handful of chemical scaffolds as CDC7 inhibitors reported to date.The progress in the development of CDC7 inhibitors patented between 2017 and 2022 is reviewed.Several CDC7 inhibitors have been progressed into clinical trials for the treatment of cancers.Declaration of interestsT Irie is a full-time employee of Carna Biosciences. M Sawa is Chief Scientific Officer of Carna Biosciences. They are co-inventors on the AS-0141 patent and stockholders in Carna Biosciences. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.Reviewer disclosuresPeer reviewers on this manuscript have no relevant financial or other relationships to disclose.Author contribution statementT Irie searched patent applications claiming CDC7 inhibitors and summarized the patents. M Sawa drafted the manuscript.Additional informationFundingThis paper was not funded.