AMG-511 is a potent and selective pan class I PI3K inhibitor exhibiting IC50 of 8, 11, 2, and 6 nM against the PI3K β, α, β, and ≤ isoforms respectively. AMG 511 reduced AKT S473 phosphorylation in a dose-dependent manner in U87 MG glioblastoma cells (IC50 = 4 nM), indicating that it inhibited PI3K pathway signaling. A downstream effector of AKT, PRAS40, was less phosphorylated as a result of AKT inhibition (IC50 = 23 nM). Additionally, U87 MG cells showed decreased phosphorylation of the mTORC1 substrates p70S6K (IC50 = 30 nM) and S6 (IC50 = 70 nM), but not 4EBP1 (T37/46).
Physicochemical Properties
| Molecular Formula | C22H28FN9O3S |
| Molecular Weight | 517.5796251297 |
| Exact Mass | 517.202 |
| Elemental Analysis | C, 51.05; H, 5.45; F, 3.67; N, 24.36; O, 9.27; S, 6.19 |
| CAS # | 1253573-53-3 |
| Related CAS # | 1253573-53-3 |
| PubChem CID | 56947516 |
| Appearance | Light yellow to yellow solid powder |
| LogP | 3.359 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 13 |
| Rotatable Bond Count | 7 |
| Heavy Atom Count | 36 |
| Complexity | 813 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | S(C)(N1CCN([C@H](C)C2C=NC(=C(C3N=C(N)N=C(C)N=3)C=2)NC2C=NC(=C(C=2)F)OC)CC1)(=O)=O |
| InChi Key | KUGIFHQBIIHRIZ-CYBMUJFWSA-N |
| InChi Code | InChI=1S/C22H28FN9O3S/c1-13(31-5-7-32(8-6-31)36(4,33)34)15-9-17(20-27-14(2)28-22(24)30-20)19(25-11-15)29-16-10-18(23)21(35-3)26-12-16/h9-13H,5-8H2,1-4H3,(H,25,29)(H2,24,27,28,30)/t13-/m1/s1 |
| Chemical Name | (R)-4-[2-[(5-fluoro-6-methoxypyridin-3-yl)amino]-5-[1-(4-methylsulfonylpiperazin-1-yl)ethyl]pyridin-3-yl]-6-methyl-1,3,5-triazin-2-amine |
| Synonyms | AMG511; AMG 511; AMG-511 |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | PI3Kα (Ki = 4 nM); PI3Kβ (Ki = 6 nM); PI3Kδ (Ki = 2 nM); PI3Kγ (Ki = 1 nM) |
| ln Vitro | AMG 511 shows the inhibition of AKT (Ser473) phosphorylation in U87 malignant glioma (MG) cells with an IC50 of 4 nM[1]. |
| ln Vivo | AMG 511 potently inhibits the targeted PI3K pathway in a mouse liver pharmacodynamic model (3-30 mg/kg; p.o.) and inhibits tumor growth in a U87 MG glioblastoma xenograft model (3-30 mg/kg; p.o.; daily; for 12 days)[1]. AMG 511 shows excellent in vivo efficacy and pharmacokinetic profile[1]. |
| References |
[1]. Selective Class I Phosphoinositide 3-kinase Inhibitors: Optimization of a Series of Pyridyltriazines Leading to the Identification of a Clinical Candidate, AMG 511. J Med Chem. 2012 Sep 13;55(17):7796-816. |
Solubility Data
| Solubility (In Vitro) |
DMSO: ~33.3 mg/mL (~64.4 mM) Water: ~8 mg/mL (~17.3 mM) Ethanol: <1 mg/mL |
| Solubility (In Vivo) |
Solubility in Formulation 1: 2 mg/mL (3.86 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9321 mL | 9.6603 mL | 19.3207 mL | |
| 5 mM | 0.3864 mL | 1.9321 mL | 3.8641 mL | |
| 10 mM | 0.1932 mL | 0.9660 mL | 1.9321 mL |