Prexasertib, a checkpoint kinase inhibitor: from preclinical data to clinical development: Cancer Chemotherapy and Pharmacology

G. Angius, S. Tomao, V. Stati, P. Vici, V. Bianco, F. Tomao

Research output: Contribution to journalArticlepeer-review


Checkpoint kinases 1 and 2 (CHK1 and CHK2) are important multifunctional proteins of the kinase family. Their main function is to regulate DNA replication and DNA damage response. If a cell is exposed to exogenous damage to its DNA, CHK1/CHK2 stops the cell cycle to give time to the cellular mechanisms to repair DNA breakage and apoptosis too, if the damage is not repairable to activate programmed cell death. CHK1/CHK2 plays a crucial role in the repair of recombination-mediated double-stranded DNA breaks. The other important functions performed by these proteins are the beginning of DNA replication, the stabilization of replication forks, the resolution of replication stress and the coordination of mitosis, even in the absence of exogenous DNA damage. Prexasertib (LY2606368) is a small ATP-competitive selective inhibitor of CHK1 and CHK2. In preclinical studies, prexasertib in monotherapy has shown to induce DNA damage and tumor cells apoptosis. The preclinical data and early clinical studies advocate the use of prexasertib in solid tumors both in monotherapy and in combination with other drugs (antimetabolites, PARP inhibitors and platinum-based chemotherapy). The safety and the efficacy of combination therapies with prexasertib need to be better evaluated in ongoing clinical trials. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
Original languageEnglish
Pages (from-to)9-20
Number of pages12
JournalCancer Chemother. Pharmacol.
Issue number1
Publication statusPublished - 2020


  • Advanced squamous cell carcinoma (SCC)
  • Checkpoint kinase 1 and 2
  • CHK inhibitors
  • CHK1
  • CHK2
  • LY2606368
  • Ovarian cancer
  • PARP inhibitors
  • Prexasertib
  • cetuximab
  • checkpoint kinase 1
  • checkpoint kinase 2
  • checkpoint kinase inhibitor
  • cytarabine
  • fludarabine
  • fluorouracil
  • folinic acid
  • gemcitabine
  • granulocyte colony stimulating factor
  • lodapolimab
  • mk 8776
  • nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase inhibitor
  • olaparib
  • pemetrexed
  • prexasertib
  • rabusertib
  • samotolisib
  • sch 900776
  • CHEK1 protein, human
  • CHEK2 protein, human
  • protein kinase inhibitor
  • pyrazine derivative
  • pyrazole derivative
  • abdominal pain
  • allergic reaction
  • anemia
  • anorexia
  • apoptosis
  • cancer combination chemotherapy
  • cancer immunotherapy
  • cancer survival
  • constipation
  • diarrhea
  • DNA damage response
  • DNA repair
  • DNA replication
  • double stranded DNA break
  • dyspepsia
  • epistaxis
  • fatigue
  • febrile neutropenia
  • fever
  • headache
  • human
  • leukopenia
  • lung infection
  • malignant neoplasm
  • maximum tolerated dose
  • monotherapy
  • multiple cycle treatment
  • nausea
  • neutropenia
  • nonhuman
  • oral mucositis
  • phase 1 clinical trial (topic)
  • phase 2 clinical trial (topic)
  • preclinical study
  • priority journal
  • progression free survival
  • recombination repair
  • Review
  • thrombocytopenia
  • vomiting
  • clinical trial (topic)
  • neoplasm
  • pathology
  • Checkpoint Kinase 1
  • Checkpoint Kinase 2
  • Clinical Trials as Topic
  • Drug Evaluation, Preclinical
  • Humans
  • Neoplasms
  • Protein Kinase Inhibitors
  • Pyrazines
  • Pyrazoles


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