| Identification | Back Directory | [Name]
ly2603618 IC-83 | [CAS]
911222-45-2 | [Synonyms]
IC-83
LY2603618
Rabusertib
ly2603618 IC-83
LY2603618, >=99%
3-(5-BroMo-4-Methyl-2-[(2s)-Morpholin-2-
(S)-1-(5-bromo-4-methyl-2-(morpholin-2-ylmethoxy)phenyl)-3-(5-methylpyrazin-2-yl)urea
N-[5-Bromo-4-methyl-2-[(2S)-2-morpholinylmethoxy]phenyl]-N'-(5-methyl-2-pyrazinyl)urea
1-[5-broMo-4-Methyl-2-[[(2S)-Morpholin-2-yl]Methoxy]phenyl]-3-(5-Methylpyrazin-2-yl)urea
N-[5-Bromo-4-methyl-2-[(2S)-2-morpholinylmethoxy]phenyl]-N'-(5-methyl-2-pyrazinyl)urea LY 2603618 | [Molecular Formula]
C18H22BrN5O3 | [MDL Number]
MFCD18633253 | [MOL File]
911222-45-2.mol | [Molecular Weight]
436.32 |
| Chemical Properties | Back Directory | [Boiling point ]
503.1±50.0 °C(Predicted) | [density ]
1.461 | [storage temp. ]
-20°C | [solubility ]
Soluble in DMSO (up to 10 mg/ml) | [form ]
solid | [pka]
12.06±0.70(Predicted) | [color ]
Off-white | [Stability:]
Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months. | [InChI]
1S/C18H22BrN5O3/c1-11-5-16(27-10-13-8-20-3-4-26-13)15(6-14(11)19)23-18(25)24-17-9-21-12(2)7-22-17/h5-7,9,13,20H,3-4,8,10H2,1-2H3,(H2,22,23,24,25)/t13-/m0/s1 | [InChIKey]
SYYBDNPGDKKJDU-ZDUSSCGKSA-N | [SMILES]
N(C1=CC(Br)=C(C)C=C1OC[C@H]1OCCNC1)C(NC1=NC=C(C)N=C1)=O |
| Questions And Answer | Back Directory | [Description]
LY2603618 is a highly selective Chk1 inhibitor with potential anti-tumor activity in a cell-free assay. IC50=7 nM, showing approximately 100-fold more potent against Chk1 than against any of the other protein kinases evaluated. | [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. Inhibition of Chk1 is predicted to enhance the effects of antimetabolites, such as gemcitabine. 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. | [In vivo]
In xenograft models, LY2603618 delays tumor growth when given in combination with pemetrexed. |
| Hazard Information | Back Directory | [Uses]
LY2603618 is a selective Chk1 inhibitor that can treat idiopathic pulmonary fibrosis. | [Definition]
ChEBI: 1-[5-bromo-4-methyl-2-[[(2S)-2-morpholinyl]methoxy]phenyl]-3-(5-methyl-2-pyrazinyl)urea is a member of ureas. | [Biological Activity]
Rabusertib (LY2603618, IC-83) is a highly selective inhibitor of Chk1 with potential antitumor activity in cell-free assays, IC50=7 nM, potency against Chk1 versus multiple other protein kinases tested 100 times higher. Rabusertib (LY2603618) induces cell cycle arrest, DNA damage response and autophagy in cancer cells. Rabusertib (LY2603618) induces bak-dependent apoptosis in AML cell lines. | [storage]
Store at -20°C | [References]
1) King?et al.?(2014),?Characterization and preclinical development of LY2603618: a selective and potent Chk1 inhibitor; Invest. New Drugs,?32?213
2) Calvo?et al.?(2014),?Preclinical analyses and phase I evaluation of LY2603618 administered in combination with pemetrexed and cisplatin in patients with advanced cancer; Invest. New Drugs,?32?955
3) Calvo?et al. (2016),?Phase I Study of CHK1 Inhibitor LY2603618 in Combination with Gemcitabine in Patients with Solid Tumors; Oncology,?91?251
4) Zhao?et al.?(2016),?Inhibition of CHK1 enhances cell death induced by the Bcl-1-selective inhibitor ABT-199 in acute myeloid leukemia cells; Oncotarget,?7?34785
5) Zhang?et al.?(2016),?Targeting radioresistant breast cancer cells by single agent CHK1 inhibitor via enhancing replication stress; Oncotarget,?7?34688 |
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| Company Name: |
Spectrum Chemical Manufacturing Corp.
|
| Telephone: |
021-021-021-67601398-809-809-809 15221380277 |
| Website: |
www.spectrumchemical.com/oa_html/index.jsp?minisite=10020&respid=22372&language=us |
| Company Name: |
NCE Biomedical Co.,Ltd.
|
| Telephone: |
4000-027-021 |24 +86-13986109188 | +86-15623472865 | +81-08033611988 |
| Website: |
www.chemicalbook.com/ShowSupplierProductsList15748/0_EN.htm |
| Company Name: |
LETOPHARM LIMITED
|
| Telephone: |
+86-21-5821 5861 |
| Website: |
www.letopharm.com |
|