LY2606368 [5-((5-(2-(3-aminopropoxy)-6-methoxyphenyl)-1H-pyrazol-3-yl)amino) pyrazine-2-carbonitrile] is an inhibitor of Checkpoint Kinase 1 (CHK1) with potential antineoplastic activity. It is discovered by Array Biopharma and being developed by Eli Lilly and Company. Lilly is responsible for all clinical development and commercialization activities. LY2606368 is advancing in Phase 2 clinical trials for cancer.
Common Name: LY2606368
Synonyms: LY-2606368; LY 2606368; LY2606368
Mechanism of Action: Kinase Inhibitior; CHK1 Inhibitor
Indication: Various Cancers; Solid Tumors
Development Stage: Phase I/II
Company: Array Biopharma/Eli Lilly
Common Name: LY2606368
Synonyms: LY-2606368; LY 2606368; LY2606368
IUPAC Name: 5-((5-(2-(3-aminopropoxy)-6-methoxyphenyl)-1H-pyrazol-3-yl) amino) pyrazine-2-carbonitrile
CAS Number: 1234015-52-1Mechanism of Action: Kinase Inhibitior; CHK1 Inhibitor
Indication: Various Cancers; Solid Tumors
Development Stage: Phase I/II
Company: Array Biopharma/Eli Lilly
LY2606368 is a selective ATP competitive inhibitor of checkpoint kinase 1 (CHK1) with IC50 value of 1.5 nM in SW1990 cells [1]. Treatment of LY2606368 is found to inhibit tumor growth and reduce the incidence of metastases and accumulation. However, LY2606368 is only administered intravenously due to its poor oral bioavailability. As a second generation inhibitor, LY2606368 distinguishes itself from other molecules in this class in that it has been shown to inhibit tumor growth when used either as monotherapy or in combination with SoC agents. The single agent activity of LY2606368 is likely related to the ability of this molecule to potently inhibit Chk1 thereby effectively interfering with its function to support normal DNA replication via regulation of origin firing and/or aspects of chromosomal dynamics during mitosis which are thought to be dependent upon Chk1 kinase activity [2].
References:
1. Wu, W.; et. al. Antitumor activity of Chk1 inhibitor LY2606368 as a single agent in SW1990 human pancreas orthotopic tumor model. Cancer Research 2012, 72(8 Supp), 1776.
2. McNeely, S. C.; et. al. Abstract A108: LY2606368, a second generation Chk1 inhibitor, inhibits growth of ovarian carcinoma xenografts either as monotherapy or in combination with standard-of-care agents. Mol Cancer Ther 2011, 10, A108.
3. ClinicalTrials.gov Chk1/2 Inhibitor (LY2606368) in Women With BRCA1/2 Mutation Associated Breast or Ovarian Cancer, Non-High Risk Triple Negative Breast Cancer, and High Grade Serous Ovarian Cancer at Low Genetic Risk. NCT02203513
