Antibodies
Nutlin-3a
- 貨號 Cat. No.
- S8059
- 規格 Size
- 5mgã€25mg
- 品牌 Brand
- Selleckchem
Description
Nutlin-3a
Catalog No.S8059
Nutlin-3a, the active enantiomer of Nutlin-3, inhibits the p53/MDM2 interaction with IC50 of 90 nM.
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
| Description | Nutlin-3a, the active enantiomer of Nutlin-3, inhibits the p53/MDM2 interaction with IC50 of 90 nM. | |||||
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| Targets | p53/MDM2 interaction | |||||
| IC50 | 90 nM [3] | |||||
| In vitro | Nutlin-3a displaces p53 from the binding pocket of MDM2 and thereby releases p53 from inhibition and proteasomal degradation, leading to induction of its downstream targets, cell cycle arrest, and apoptosis. Seven days of incubation with 10 μM nutlin-3a led to >90% inhibition of NIH3T3 cells’ growth[1]. Nutlin-3a stabilizes and activates p53, and induces p21 expression in a dose-dependent manner[1]. Nutlin-3a effectively depletes the S-phase compartment to 0.2-2% and increases the G1- and G2/M-phase compartments[1]. Nutlin-3a induces apoptosis in ~60% of SJSA-1 and MHM cells after 40 h, which increased further after 60 h (85% and 65%, respectively) [1]. | |||||
| In vivo | Nutlin-3a suppresses xenograft growth in a dose-dependent fashion with the highest dose (200 mg/kg) showing a substantial tumor shrinkage [1]. Nutlin-3 is a selective activator of the p53 pathway in vivo and highly efficacious against SJSA-1 osteosarcoma tumors[1]. Tumors with wild-type p53 and mdm2 gene amplification will respond best to therapy with Nutlin-3a. | |||||
| Features | Highly selective MDM2 inhibitor with a much lower effect on MDMX. Most effective on tumors with wild type p53. | |||||
Protocol(Only for Reference)
Kinase Assay: [3]
| Biacore studies | Competition assays are performed on a Biacore S51. A Series S Sensor chip CM5 is derivatized for immobilization of a PentaHis antibody for capture of the His-tagged p53. The level of capture is ~ 200 response units (1 response unit corresponds to 1 pg of protein per mm 2). The concentration of MDM2 protein is kept constant at 300 nM. Test compounds are dissolved in DMSO at 10 mM and further diluted to make a concentration series of inhibitor in each MDM2 test sample. The assays are run at 25 °C in running buffer (10 mM Hepes, 0.15 M NaCl, 2% DMSO). MDM2-p53 binding in the presence of inhibitor is calculated as a percentage of binding in the absence of inhibitor and IC50 is calculated using Microsoft Excel |
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Cell Assay: [2]
| Cell lines | OSA, T778, RMS13, U2OS, SaOS-2 |
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| Concentrations | ~5 μM |
| Incubation Time | 120 h |
| Method | SRB |
Animal Study: [1]
| Animal Models | SJSA-1 xenograft |
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| Dosages | 50, 100, 200 mg/kg twice daily |
| Administration | oral |
| Solubility | 1% hyroxyethylcellulose/0.2% Tween 80, 15 mg/mL |
References
Chemical Information
| Molecular Weight (MW) | 581.49 |
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| Formula | C30H30Cl2N4O4 |
| CAS No. | 675576-98-4 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | (-)-Nutlin-3 |
| Solubility (25°C) * | In vitro | DMSO | 100 mg/mL (171 mM) |
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| Water | <1 mg/mL (<1 mM) | ||
| Ethanol | 100 mg/mL (171 mM) | ||
| In vivo | 1% hyroxyethylcellulose/0.2% Tween 80, | 15 mg/mL | |
| * <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 | 2-Piperazinone, 4-[[(4S,5R)-4,5-bis(4-chlorophenyl)-4,5-dihydro-2-[4-methoxy-2-(1-methylethoxy)phenyl]-1H-imidazol-1-yl]carbonyl]- |
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