AMG-47Adestabilizer of the KRAS oncoprotein CAS# 882663-88-9 |
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Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
| Cas No. | 882663-88-9 | SDF | Download SDF |
| PubChem ID | 16086114 | Appearance | Powder |
| Formula | C29H28F3N5O2 | M.Wt | 535.56 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : ≥ 34 mg/mL (63.48 mM) *"≥" means soluble, but saturation unknown. | ||
| Chemical Name | 4-methyl-3-[2-(2-morpholin-4-ylethylamino)quinazolin-6-yl]-N-[3-(trifluoromethyl)phenyl]benzamide | ||
| SMILES | CC1=C(C=C(C=C1)C(=O)NC2=CC=CC(=C2)C(F)(F)F)C3=CC4=CN=C(N=C4C=C3)NCCN5CCOCC5 | ||
| Standard InChIKey | DVRSTRMZTAPMKO-UHFFFAOYSA-N | ||
| Standard InChI | InChI=1S/C29H28F3N5O2/c1-19-5-6-21(27(38)35-24-4-2-3-23(17-24)29(30,31)32)16-25(19)20-7-8-26-22(15-20)18-34-28(36-26)33-9-10-37-11-13-39-14-12-37/h2-8,15-18H,9-14H2,1H3,(H,35,38)(H,33,34,36) | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | AMG-47a is a potent inhibitor of Lck and T cell proliferation; exhibits anti-inflammatory activity (ED50 = 11 mg/kg) in the anti-CD3 induced production of IL-2 in mice.
IC50 value:
Target: Lck inhibitor
In several other in vitro assays, AMG-47a displays subnanomolar inhibition against Lck, and low (<10 nM) inhibition against other hard to inhibit kinases such as KDR and SRC and MAPK α (p38α). In addition, at slightly higher doses but well under 10 μM, AMG-47a effectively inhibits the JNK family of kinases including TYK2 at ~ 1.2 μM. AMG-47a selectively reduced the levels of EGFP-KRASG12V protein but did not affect EGFP protein in cells. References: | |||||
AMG-47A Dilution Calculator
AMG-47A Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 1.8672 mL | 9.336 mL | 18.672 mL | 37.3441 mL | 46.6801 mL |
| 5 mM | 0.3734 mL | 1.8672 mL | 3.7344 mL | 7.4688 mL | 9.336 mL |
| 10 mM | 0.1867 mL | 0.9336 mL | 1.8672 mL | 3.7344 mL | 4.668 mL |
| 50 mM | 0.0373 mL | 0.1867 mL | 0.3734 mL | 0.7469 mL | 0.9336 mL |
| 100 mM | 0.0187 mL | 0.0934 mL | 0.1867 mL | 0.3734 mL | 0.4668 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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AMG-47A is a destabilizer of the KRAS oncoprotein.
Ras is a small GTPase that involves in numerous cellular signaling pathways governing growth, survival, and motility. In humans, there are three Ras genes: KRAS, HRAS, and NRAS. Oncogenic
mutations in all three Ras family members have been identified in human cancers. In particular, KRAS is one of the most frequently mutated oncogenes across cancer types.[1]
In the HeLa EGFP-KRASG12V cells, 48-hour treatment of AMG-47a has a 30–40% decrease in EGFP signal, treating cells for 3 and 5 days shows the similar results. AMG-47a selectively affects EGFP-KRASG12V protein levels. AMG-47a also has a mild effect on EGFP-KRASG12V protein levels after three days. The loss of EGFP-KRASG12V signal plateaus at 50% for AMG-47a. [1]
References:
1. Carver J, Dexheimer TS, Hsu D et al. A high-throughput assay for small molecule destabilizers of the KRASoncoprotein. PLoS One. 2014 Aug 5;9(8):e103836
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A high-throughput assay for small molecule destabilizers of the KRAS oncoprotein.[Pubmed:25093678]
PLoS One. 2014 Aug 5;9(8):e103836.
Mutations in the Ras family of small GTPases, particularly KRAS, occur at high frequencies in cancer and represent a major unmet therapeutic need due to the lack of effective targeted therapies. Past efforts directed at inhibiting the activity of the Ras oncoprotein have proved difficult. We propose an alternative approach to target Ras by eliminating Ras protein from cells with pharmacological means. In this study, we developed a cell-based, high-content screening platform to identify small molecules that could promote the degradation of the KRAS oncoprotein. We generated an EGFP-KRASG12V fluorescence reporter system and implemented it for automated screening in 1536-well plates using high-throughput cellular imaging. We screened a library of clinically relevant compounds at wide dose range and identified Ponatinib and AMG-47A as two candidate compounds that selectively reduced the levels of EGFP-KRASG12V protein but did not affect EGFP protein in cells. This proof-of-principle study demonstrates that it is feasible to use a high-throughput screen to identify compounds that promote the degradation of the Ras oncoprotein as a new approach to target Ras.
