[CAS NO. 1184843-57-9] SAR-020106
PRODUCTS SPECIFICATIONS [1184843-57-9]
DESCRIPTION [1184843-57-9]
Overview
| MDL | MFCD28155090 |
|---|---|
| Molecular Weight | 382.85 |
| Molecular Formula | C19H19ClN6O |
| SMILES | N#CC1=NC=C(NC2=CC3=C(C=N2)C(Cl)=CC=C3)N=C1O[C@H](C)CN(C)C |
Summary
SAR-020106 is an ATP-competitive, potent, and selective CHK1 inhibitor with an IC 50 of 13.3 nM for human CHK1 . SAR-020106 shows excellent selectivity over CHK2 . SAR-020106 significantly enhances the cell killing of Gemcitabine and SN38 by 3- to 29-fold in several colon tumor lines and in a p53-dependent fashion. SAR-020106 can enhance antitumor activity with selected anticancer drugs [1] [2] .
IC50 & Target
|
Chk1 13.3 nM (IC 50 ) |
In Vitro
SAR-020106 (0.1-1 μM; 23 hours) abrogates an Etoposide-induced S and G2 arrest
[1]
.
SAR-020106 is capable of abrogating Etoposide-induced cell cycle arrest with an IC
50
of 55 nM and 91 nM in HT29 and SW620 cells, respectively. SAR-020106 is relatively nontoxic with a GI
50
of 0.48 μM in HT29 and 2 μM in SW620, resulting in an activity index of 8.7 and 22, respectively. SAR-020106 inhibits cytotoxic drug-induced autophosphorylation of CHK1 at S296 and blocks the phosphorylation of CDK1 at Y15 in a dose-dependent fashion
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
SAR-020106 (40 mg/kg; i.p.; administered on days 0, 1, 7, 8, 14, and 15) in combination with Irinotecan potentiates the antitumor activity in SW620 xenografts [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Nude mice bearing SW620 xenograft tumors [1] |
| Dosage: | 40 mg/kg |
| Administration: | I.p.; administered on days 0, 1, 7, 8, 14, and 15 |
| Result: | There was a clear decrease in tumor growth associated with the combination with tumors reaching 300% by 12.5 days. |
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 : 5 mg/mL ( 13.06 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.6120 mL | 13.0599 mL | 26.1199 mL |
| 5 mM | 0.5224 mL | 2.6120 mL | 5.2240 mL |
| 10 mM | 0.2612 mL | 1.3060 mL | 2.6120 mL |
References
- [1] Walton MI, et al. The preclinical pharmacology and therapeutic activity of the novel CHK1 inhibitor SAR-020106. Mol Cancer Ther. 2010;9(1):89-100.
- [2] Reader JC, et al. Structure-guided evolution of potent and selective CHK1 inhibitors through scaffold morphing. J Med Chem. 2011;54(24):8328-8342.