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Last Updated: 01/25/17

Information below provided by the Pharmaceutical Company.

Prexasertib (LY2606368)

Agent Description

Prexasertib is a small molecule inhibitor of checkpoint kinase 1 and is being investigated both as a monotherapy and in combination with chemotherapy, targeted agents or radiation. It is in phase I clinical trials and in clinical trials in patients with head and neck cancer and small cell lung cancer.

http://www.lillyoncologypipeline.com/molecule/chk-1-inhibitor/overview External Link

Mechanism of Action

Prexasertib is a small molecule that in vitro preferentially binds to and inhibits CHK1 and, to a lesser extent, inhibits CHK2, thus inducing DNA double-strand breaks, a loss in checkpoint function, increased replication stress, and cell death.

Classification

Checkpoint kinase 1 inhibitor

Molecular Targets

Checkpoint kinase 1 (CHK1) is a global regulator of the mammalian cell cycle. In addition to regulating DNA damage checkpoints, CHK1 plays a central role in normal DNA replication, resolving replication stress, progression to mitosis, and cytokinesis. Inhibition of CHK1 in the absence of DNA damage can cause impaired DNA replication, loss of DNA damage checkpoints, premature entry into mitosis with highly fragmented DNA, and cell death via replication catastrophe.

Monograph

Prexasertib is not currently approved for any indication. On-going trials for this agent are listed on https://clinicaltrials.gov. Nonclinical data has been published (Mol Cancer Ther. 2015 Sep;14(9):2004-13) as has clinical data from the first-in-man study (J Clin Oncol. 2016 May 20;34(15):1764-71).

Studies of Interest

On-going trials for this agent are listed on https://clinicaltrials.gov. Duplicates of these studies would not be supported.

Information collaborator would like included in investigator proposals

N/A