Antibodies
Lomeguatrib
- 貨號 Cat. No.
- S8056
- 規格 Size
- 10mgã€50mg
- 品牌 Brand
- Selleckchem
Description
Lomeguatrib
Catalog No.S8056
Lomeguatrib is a potent inhibitor of O6-alkylguanine-DNA-alkyltransferase with IC50 of 5 nM.
| Size | Price | Stock | Quantity | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| |||||||||||
Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
| Description | Lomeguatrib is a potent inhibitor of O6-alkylguanine-DNA-alkyltransferase with IC50 of 5 nM. | |||||
|---|---|---|---|---|---|---|
| Targets | O6-alkylguanine-DNA-alkyltransferase | |||||
| IC50 | 5 nM [1] | |||||
| In vitro | Lomeguatrib inactivates O6-alkylguanine-DNA-alkyltransferase (ATase) with a IC50 10-fold lower than O6-Benzylguanine. Lomeguatrib inhibits the activity of ATase in Raji cells with IC50 of 10 nM. [1] Lomeguatrib effectively inactivates MGMT in MCF-7 cells with IC50 of ~6nM ). Lomeguatrib (10 μM ) substantially increases the growth inhibitory effects of temozolomide in MCF-7 cells (D60= 10 μM with Lomeguatrib vs 400 μM without).[2] | |||||
| In vivo | Lomeguatrib (20 mg/kg/day for 5 days) combined with temozolomide (100 mg/kg/day for 5 days) produces a substantial tumour growth delay: median tumour quintupling time is increased by 22 days without any significant increase in toxicity, while neither of the two drugs administrated along show any antitumor activity. [2]Lomeguatrib inactivates ATase and enhances the anti-tumour effect of temozolomide in A375M human melanoma xenografts model. Lomeguatrib, at a single dose of 20 mg/kg i.p., produces complete ATase depletion in tumor within 2 hr. Temozolomide (100 g/kg/day) significantly delays growth of the A375M tumour xenograft with an estimated delay in the time for tumour to quintuple in size of 9.6 days. Addition of Lomeguatrib to temozolomide significantly enhances the latter’s effect, delaying the quintupling time a further 8.7 days. Moreover, the Lomeguatrib combination results in considerably less toxicity (0/9 vs. 2/9 deaths; 6.84% weight loss vs. 9.48%). Lomeguatrib alone has no significant effect on tumour growth. [3] | |||||
| Features | ||||||
Protocol(Only for Reference)
Kinase Assay: [1]
| ATases activity assay | The cDNA cloning and overexpression of the human ATase are performed. Purification of the recombinant proteins is achieved by DEAE-cellulose ion-exchange chromatography. The ATase protein is partially purified by ammonium sulfate precipitation (30-60%) and dialyzed against 10 mM Tris-HCl (pH 7.5), 1 mM dithiothreitol (DTT), 2 mM EDTA, 10% glycerol, before loading onto a DEAE-cellulose column. The ATase is then eluted with a 0-0.1 M NaCl gradient. The purified human ATase protein retains activity for more than 1 year when stored at high concentration at -20 ℃ in buffer I [50 mM Tris-HCl (pH 8.3)/3 mM DTT/1 mM EDTA] and could be thawed and refrozen several times without substantial loss of activity. Compounds to be tested are dissolved in DMSO to a final concentration of 10 mM and diluted just before use in buffer I containing 1 mg/mL bovine serum albumin (IBSA). Recombinant ATase is diluted in IBSA and titrated in order that the reaction be conducted under ATase, and not substrate, limiting conditions. In each assay, fixed amounts of ATase (50 -60 fmol) are incubated with varying amounts of O6-benzylguanine, or test compound, in a total volume of 200 μL of IBSA containing 10 μg of calf thymus DNA at 37 ℃ for 1 h. The 3H-methylated DNA substrate (100 μL containing 4 μg of DNA and 100 fmol of O6-benzylguanine is added and incubation continued at 37 ℃for 1 h, until the reaction is completed. Following acid hydrolysis of the DNA, the 3H-methylated protein is recovered and quantitated by liquid scintillation counting. Samples are typically assayed in duplicate and experiments repeated several times. |
|---|
References
Chemical Information
| Molecular Weight (MW) | 326.17 |
|---|---|
| Formula | C10H8BrN5OS |
| CAS No. | 192441-08-0 |
| Storage | 3 years -20℃Powder |
|---|---|
| 6 months-80℃in DMSO | |
| Syonnyms | PaTrin-2 |
| Solubility (25°C) * | In vitro | DMSO | 65 mg/mL (199 mM) |
|---|---|---|---|
| Water | <1 mg/mL (<1 mM) | ||
| Ethanol | <1 mg/mL (<1 mM) | ||
| * <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. | |||
| Chemical Name | 6-[(4-Bromo-2-thienyl)methoxy]-9H-p-urin-2-amine |
|---|
