| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg | |||
| 100mg | |||
| 250mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
PI3Kα (Ki = 4 nM); PI3Kβ (Ki = 6 nM); PI3Kδ (Ki = 2 nM); PI3Kγ (Ki = 1 nM)
AMG-511 targets class I phosphoinositide 3-kinases (PI3Ks) with Ki values of 4 nM, 6 nM, 2 nM, and 1 nM for PI3Kα, β, δ, and γ, respectively. It is highly selective over mTOR (IC50 > 10,000 nM), hVPS34 (IC50 > 9,000 nM), DNAPK (IC50 = 12,000 nM), and a broad panel of other protein kinases. PI3K signaling plays a critical role in cell proliferation, survival, and metabolism. |
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| ln Vitro |
AMG 511 shows the inhibition of AKT (Ser473) phosphorylation in U87 malignant glioma (MG) cells with an IC50 of 4 nM[1].
In vitro, AMG-511 inhibits PI3K pathway signaling in U87 MG glioblastoma cells as determined by dose-dependent reduction in AKT S473 phosphorylation with an IC50 of 4 nM. It shows potent inhibition of class I PI3Ks with Ki values of 4 nM (α), 6 nM (β), 2 nM (δ), and 1 nM (γ). AMG-511 demonstrates excellent selectivity over mTOR and other kinases. The compound's in vitro potency is confirmed across multiple cell lines. |
| 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].
In vivo, AMG-511 potently inhibits the targeted PI3K pathway in a mouse liver pharmacodynamic model at 3-30 mg/kg (oral administration). It inhibits tumor growth in a U87 MG glioblastoma xenograft model at 3-30 mg/kg (oral; daily; for 12 days). AMG-511 shows excellent in vivo efficacy and a favorable pharmacokinetic profile. The compound's anti-tumor activity is dose-dependent and associated with PI3K pathway inhibition. |
| Enzyme Assay |
For in vitro kinase assays, AMG-511 is tested against recombinant PI3K isoforms (α, β, δ, γ) using in vitro kinase activity assays. The compound is incubated with the enzyme and its substrate, and the incorporation of phosphate is measured. Ki values are determined from dose-response curves. Selectivity profiling is performed against a broad panel of kinases including mTOR, hVPS34, and DNAPK. IC50 values are determined for each kinase tested.
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| Cell Assay |
For in vitro cell-based studies, U87 MG glioblastoma cells are treated with AMG-511 at various concentrations. PI3K pathway inhibition is assessed by measuring AKT S473 phosphorylation via Western blot analysis. The IC50 for inhibition of AKT phosphorylation is determined from dose-response curves. Cell viability and proliferation can be assessed using MTT or CellTiter-Glo assays. The effect of AMG-511 on downstream PI3K signaling targets can be evaluated by Western blot analysis.
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| Animal Protocol |
In vivo animal studies with AMG-511 are conducted in female CD1 NU/NU mice bearing U87 MG glioblastoma xenografts. AMG-511 is administered orally at doses of 1, 3, and 10 mg/kg daily for 12 days. Tumor growth is measured over time using calipers, and tumor growth inhibition is calculated. For pharmacodynamic studies, mice are treated at 3-30 mg/kg (oral), and liver tissues are collected for assessment of PI3K pathway inhibition.
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| ADME/Pharmacokinetics |
AMG-511 is orally bioavailable with excellent in vivo efficacy and a favorable pharmacokinetic profile. The compound shows potent activity in mouse models at oral doses of 3-30 mg/kg. AMG-511 has a molecular weight of 517.58 g/mol. It is soluble in DMSO. Detailed PK parameters such as half-life, Cmax, AUC, and bioavailability have been reported in the literature.
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| Toxicity/Toxicokinetics |
Toxicological data for AMG-511 are limited, as the compound is a research chemical not intended for human therapeutic use. The compound is typically handled with standard laboratory safety precautions. No comprehensive toxicology studies have been reported in the available literature. AMG-511 was identified as a clinical candidate, suggesting it has undergone some preclinical safety evaluation, but detailed toxicity data are not publicly available.
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| References | |
| Additional Infomation |
AMG-511 is a potent and orally available pan-class I PI3K inhibitor identified as a clinical candidate through optimization of a series of pyridyltriazines. It exhibits excellent selectivity over mTOR and other kinases. AMG-511 has been investigated for its potential therapeutic applications in cancer, particularly in glioblastoma and other solid tumors. The compound is not an FDA-approved drug and is not commercially available as a pharmaceutical product.
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| Molecular Formula |
C22H28FN9O3S
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|---|---|
| Molecular Weight |
517.5796251297
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| Exact Mass |
517.202
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| Elemental Analysis |
C, 51.05; H, 5.45; F, 3.67; N, 24.36; O, 9.27; S, 6.19
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| CAS # |
1253573-53-3
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| Related CAS # |
1253573-53-3
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| PubChem CID |
56947516
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
3.359
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
13
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
36
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| Complexity |
813
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| Defined Atom Stereocenter Count |
1
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| 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
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| InChi Key |
KUGIFHQBIIHRIZ-CYBMUJFWSA-N
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| 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
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| 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
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| Synonyms |
AMG511; AMG 511; AMG-511
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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 |
| 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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| Solubility (In Vitro) |
DMSO: ~33.3 mg/mL (~64.4 mM)
Water: ~8 mg/mL (~17.3 mM) Ethanol: <1 mg/mL |
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| 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 |
*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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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