LY2603618

• Catalog No.: S2626
• CAS Number: 911222-45-2
• M. F.: C18H22BrN5O3
• M. W.: 436.30298
• Storage: -20°C

SYNONYMS

• 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
• Synonyms: IC-83; LY 2603618

DATABASE IDS

• CAS Number: 911222-45-2

PROPERTIES

• Target: CHK
• Salt Data: Free Base
• Storage Condition: -20°C

DETAILS

Description (English)

Biological Activity

• Description: LY2603618 (IC-83) is a selective Chk1 inhibitor with potential anti-tumor activity.
• Targets: Chk1
• 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.

References

• References: [1] Dai Y, et al. Clin Cancer Res, 2010, 16(2), 376-383.
• References: [2] Emiliano Calvo1, et al. Mol Cancer Ther, 2011, A94.
• References: [3] Govindan R. J Thorac Oncol, 2011, 6(11 Suppl 4), S1757.

REFERENCES

• Dai Y, et al. Clin Cancer Res, 2010, 16(2), 376-383.
• Emiliano Calvo1, et al. Mol Cancer Ther, 2011, A94.
• Govindan R. J Thorac Oncol, 2011, 6(11 Suppl 4), S1757.