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A-176120 is a potent and selective inhibitor of the farnesyltransferase with IC50 of 1.2+/-0.3 nM. It is more selective over the closely related enzymes geranylgeranyltransferase I (GGTaseI) (IC(50) 423+/-1.8 nM), geranylgeranyltransferase II (GGTaseII) (IC(50) 3000 nM) and squalene synthase (SSase) (IC(50)>10000 nM). A-176120 inhibited ras processing in H-ras-transformed NIH3T3 cells and HCT116 K-ras-mutated cells (ED(50) 1.6 and 0.5 microM, respectively). The anti-angiogenic potential of A-176120 was demonstrated by a decrease in Ras processing, cell proliferation and capillary structure formation of human umbilical vein endothelial cells (HUVEC), and a decrease in the secretion of vascular endothelial growth factor (VEGF) from HCT116 cells. In vivo, A-176120 reduced H-ras NIH3T3 tumour growth and extended the lifespan of nude mice inoculated with H- or K-ras-transformed NIH3T3 cells. .
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Physicochemical Properties
| Molecular Formula |
C33H29NO9
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| Molecular Weight |
583.58466
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| Exact Mass |
583.184
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| CAS # |
185049-54-1
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| Related CAS # |
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| PubChem CID |
9829802
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
6.123
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
43
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| Complexity |
964
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCOc1ccccc1CN(Cc2cccc(c2)Oc3ccc(cc3)C)C(=O)c4cc(c(cc4C(=O)O)C(=O)O)C(=O)O
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| InChi Key |
NHCMSBSXCWMLKE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C33H29NO9/c1-3-42-29-10-5-4-8-22(29)19-34(18-21-7-6-9-24(15-21)43-23-13-11-20(2)12-14-23)30(35)25-16-27(32(38)39)28(33(40)41)17-26(25)31(36)37/h4-17H,3,18-19H2,1-2H3,(H,36,37)(H,38,39)(H,40,41)
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| Chemical Name |
5-[(2-ethoxyphenyl)methyl-[[3-(4-methylphenoxy)phenyl]methyl]carbamoyl]benzene-1,2,4-tricarboxylic acid
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| Synonyms |
| A-176120; A 176120; A 176120 |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder-20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Biological Activity
| ln Vitro |
In vitro activity:
Kinase Assay:
Cell Assay: |
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| ln Vivo |
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| Animal Protocol |
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| References |
Eur J Cancer.2000 Jun;36(9):1161-70.
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Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
(Please use freshly prepared in vivo formulations for optimal results.)
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| Preparing Stock Solutions |
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1 mg |
5 mg |
10 mg |
| 1 mM |
1.7136 mL |
8.5678 mL |
17.1356 mL |
| 5 mM |
0.3427 mL |
1.7136 mL |
3.4271 mL |
| 10 mM |
0.1714 mL |
0.8568 mL |
1.7136 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles. |
