Substance
ID:74060
Names and Identifiers
Synonyms
IC-83LY 2603618LY2603618
IUPAC name
3-{5-bromo-4-methyl-2-[(2S)-morpholin-2-ylmethoxy]phenyl}-1-(5-methylpyrazin-2-yl)urea
IUPAC Traditional name
3-{5-bromo-4-methyl-2-[(2S)-morpholin-2-ylmethoxy]phenyl}-1-(5-methylpyrazin-2-yl)urea
Registration numbers
CAS Number
Properties
Product Information
Salt Data
Free Base
Safety Information
Storage Condition
-20°C
Pharmacology Properties
Target
CHK
Molecule Details
Biological Activity
Description
LY2603618 (IC-83) is a selective Chk1 inhibitor with potential anti-tumor activity.
Targets
Chk1
IC50
In Vitro
Chk1 is an ATP-dependent serine-threonine kinase and a key component in the DNA replication-monitoring checkpoint system activated by double-stranded breaks (DSBs). Chk1 contributes to all currently defined cell cycle checkpoints, including G1/S, intra-S-phase, G2/M, and the mitotic spindle checkpoint. By inhibiting the activity of chk1, LY2603618 prevents the repair of DNA caused by DNA-damaging agents, thus potentiating the antitumor efficacies of various chemotherapeutic agents. However, preclinical data involving LY2603618 has not been published until now. [1] Inhibition of Chk1 is predicted to enhance the effects of antimetabolites, such as gemcitabine. [2] LY2603618 treatment impairs DNA synthesis, increases DNA damage (via mitotic defects), induces apoptosis, and has synergistic activity with pemetrexed, especially in p53 mutant tumor cells. [3]
In Vivo
In xenograft models, LY2603618 delays tumor growth when given in combination with pemetrexed. [3]
Clinical Trials
A Phase I study of to assess the effect of LY2603618 on the metabolic pathway of Desipramine is ongoing.
Features
Molecular Spectra
No Data Available
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References
• Govindan R. J Thorac Oncol, 2011, 6(11 Suppl 4), S1757.
• Dai Y, et al. Clin Cancer Res, 2010, 16(2), 376-383.
• Emiliano Calvo1, et al. Mol Cancer Ther, 2011, A94.