[CAS NO. 911222-45-2] Rabusertib
PRODUCTS SPECIFICATIONS [911222-45-2]
DESCRIPTION [911222-45-2]
Overview
| MDL | MFCD18633253 |
|---|---|
| Molecular Weight | 436.30 |
| Molecular Formula | C18H22BrN5O3 |
| SMILES | BrC(C=C1NC(NC2=NC=C(N=C2)C)=O)=C(C=C1OC[C@H]3OCCNC3)C |
10 Publications Citing Use of MCE
- [1]Sci Transl Med. 2021 Jan 20;13(577):eaba7401.
- [2]Sci Transl Med. 2018 Jul 18;10(450):eaaq1093.
- [3]Nucleic Acids Res. 2021 Apr 6;49(6):3322-3337.
- [4]Dev Cell. 2022 Feb 23;S1534-5807(22)00079-X.
- [5]Cell Syst. 2020 Jan 22;10(1):66-81.e11.
- [6]Cell Syst. 2020 Jan 22;10(1):66-81.e11.
- [7]Cancers (Basel). 2023, 15(3), 850.
- [8]Cell Prolif. 2020 Oct;53(10):e12895.
- [9]Cancer Biol Ther. 2022 Jan 9;1-14.
- [10]Harvard Medical School LINCS LIBRARY
Summary
Rabusertib (LY2603618) is a potent and selective inhibitor of Chk1 with an IC 50 of 7 nM.
IC50 & Target
|
Chk1 7 nM (IC 50 ) |
Chk2 12000 nM (IC 50 ) |
PDK1 893 nM (IC 50 ) |
CAMK2 1550 nM (IC 50 ) |
VEGFR3 2128 nM (IC 50 ) |
MET 2200 nM (IC 50 ) |
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|
JNK1 4930 nM (IC 50 ) |
RSK2 5700 nM (IC 50 ) |
NTRK1 12000 nM (IC 50 ) |
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In Vitro
Rabusertib (LY2603618) is a highly effective inhibitor of multiple aspects of Chk1 biology. Rabusertib (LY2603618) is tested against a panel of 51 diverse protein kinases in vitro. With an IC 50 of 7 nM for Chk1, Rabusertib (LY2603618) is approximately 100-fold more potent against Chk1 than against any of the other protein kinases evaluated (PDK1, IC 50 =893 nM, others >1000 nM). Rabusertib (LY2603618) effectively reduced Chk1 autophosphorylation with an EC 50 of 430 nM. Inhibition of Chk1 by Rabusertib (LY2603618) also effectively abrogated the G 2 /M DNA damage checkpoint in cells treated with DNA damaging agents. Treatment of cells with Rabusertib (LY2603618) produced a cellular phenotype similar to that reported for depletion of Chk1 by RNAi. Inhibition of intracellular Chk1 by Rabusertib (LY2603618) results in impaired DNA synthesis, elevated H2A.X phosphorylation indicative of DNA damage and premature entry into mitosis [1] . Treatments of the SK-N-BE(2) cells with variable concentrations of Rabusertib (LY2603618) results in dose-dependent inhibition of cell growth determined by MTT assays with an IC 50 of 10.81 µM [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
Mice bearing Calu-6 xenografts are treated with 150 mg/kg (IP) Gemcitabine and a single simultaneous 200 mg/kg oral dose of Rabusertib (LY2603618). 200 mg/kg of Rabusertib (LY2603618) is sufficient to inhibit 85 % of Chk1 autophosphorylation in vivo at 2 h. Rabusertib (LY2603618) effectively reduces Gemcitabine-induced phosphorylation on Tlk serine 695 as well, supporting the cited report with a selective chemical inhibitor of Chk1 [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT01296568 | Eli Lilly and Company |
Advanced Cancer
|
February 2011 | Phase 1 |
| NCT01358968 | Eli Lilly and Company |
Cancer
|
June 2011 | Phase 1 |
| NCT00988858 | Eli Lilly and Company |
Non Small Cell Lung Cancer
|
November 2009 | Phase 2 |
| NCT01341457 | Eli Lilly and Company |
Solid Tumors
|
May 2011 | Phase 1 |
| NCT00839332 | Eli Lilly and Company |
Pancreatic Neoplasms
|
February 2009 | Phase 1|Phase 2 |
| NCT01139775 | Eli Lilly and Company |
Non Small Cell Lung Cancer
|
February 2011 | Phase 1|Phase 2 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 31.25 mg/mL ( 71.63 mM ; ultrasonic and warming and heat to 60°C)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.2920 mL | 11.4600 mL | 22.9200 mL |
| 5 mM | 0.4584 mL | 2.2920 mL | 4.5840 mL |
| 10 mM | 0.2292 mL | 1.1460 mL | 2.2920 mL |
References
- [1] King C, et al. Characterization and preclinical development of LY2603618: a selective and potent Chk1 inhibitor. Invest New Drugs. 2014 Apr;32(2):213-26.
- [2] Wang G, et al. Panobinostat synergistically enhances the cytotoxic effects of cisplatin, doxorubicin or etoposide on high-risk neuroblastoma cells. PLoS One. 2013 Sep 30;8(9):e76662.