AMG 511 is a potent and orally available pan inhibitor of class I PI3K s, with K i s of 4 nM, 6 nM, 2 nM and 1 nM for PI3Kα , β, δ and γ, respectively. AMG 511 significantly suppresses PI3K signaling that is indicated by p-Akt (Ser473) decrease. AMG 511 exhibits anti-tumor activity in mouse glioblastoma xenograft model
In Vitro
AMG 511 shows the inhibition of AKT (Ser473) phosphorylation in U87 malignant glioma (MG) cells with an IC 50 of 4 nM. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
AMG 511 potently blocks 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) . AMG 511 shows excellent in vivo efficacy and pharmacokinetic profile . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Female CD1 NU/NU mice, with U87 MG glioblastoma xenograft model Dosage: 1 mg/kg, 3 mg/kg, 10 mg/kg Administration: Oral administration, daily, for 12 days Result: Inhibited tumor growth. Animal Model: Male Sprague-Dawley rats Dosage: 1 mg/kg Administration: Oral administration (Pharmacokinetic Analysis) Result: Had a superior pharmacokinetic profile with low clearance (0.4 L/h/kg, 12% of liver blood flow), good oral bioavailability (F = 60%), and a commensurate high oral exposure (AUC = 5.0 μM·h).
Form:Solid
IC50& Target:PI3Kα 4 nM (Ki) PI3Kβ 6 nM (Ki) PI3Kδ 2 nM (Ki) PI3Kγ 1 nM (Ki)
Taxonomy Tree
| Kingdom | Organic compounds |
|---|---|
| Superclass | Organoheterocyclic compounds |
| Classe | Triazines |
| Subclass | Aminotriazines |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Aminotriazines |
| Alternative Parents | Alkyl aryl ethers Aminopyridines and derivatives Aralkylamines N-alkylpiperazines 1,3,5-triazines Aryl fluorides Imidolactams Organic sulfonamides Organosulfonamides Sulfonyls Heteroaromatic compounds Trialkylamines Azacyclic compounds Secondary amines Hydrocarbon derivatives Primary amines Organic oxides Organofluorides |
| Molecular Framework | Aromatic heteromonocyclic compounds |
| Substituents | Alkyl aryl ether - Aminopyridine - Amino-1,3,5-triazine - Aminotriazine - N-alkylpiperazine - Aralkylamine - Piperazine - 1,4-diazinane - Pyridine - Aryl halide - Organic sulfonic acid amide - Organosulfonic acid amide - 1,3,5-triazine - Aryl fluoride - Imidolactam - Heteroaromatic compound - Organosulfonic acid or derivatives - Organic sulfonic acid or derivatives - Sulfonyl - Tertiary amine - Tertiary aliphatic amine - Azacycle - Secondary amine - Ether - Organofluoride - Organohalogen compound - Organic oxygen compound - Primary amine - Amine - Organic nitrogen compound - Hydrocarbon derivative - Organic oxide - Organonitrogen compound - Organooxygen compound - Organosulfur compound - Aromatic heteromonocyclic compound |
| Descrição | This compound belongs to the class of organic compounds known as aminotriazines. These are organic compounds containing an amino group attached to a triazine ring. |
| External Descriptors | Not available |
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| Solubilidade | DMSO : 33.33 mg/mL (64.40 mM; Need ultrasonic) |
|---|---|
| Peso molecular | 517.600 g/mol |
| XLogP3 | 1.100 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 13 |
| Rotatable Bond Count | 7 |
| Exact Mass | 517.202 Da |
| Monoisotopic Mass | 517.202 Da |
| Topological Polar Surface Area | 161.000 Ų |
| Heavy Atom Count | 36 |
| Formal Charge | 0 |
| Complexity | 813.000 |
| Isotope Atom Count | 0 |
| Defined Atom Stereocenter Count | 1 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| The total count of all stereochemical bonds | 0 |
| Covalently-Bonded Unit Count | 1 |
