| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
PI3Kα (IC50 = 3.4 nM); PI3Kβ (IC50 = 34 nM); PI3Kδ (IC50 = 16 nM); PI3Kγ (IC50 = 1 nM); mTOR (IC50 = 4.7 nM)
PI3Kα (IC50 = 3.4 nM) PI3Kβ (IC50 = 34 nM) PI3Kδ (IC50 = 16 nM) PI3Kγ (IC50 = 1 nM) mTOR (IC50 = 4.7 nM) All enzyme IC50 values were determined using HTRF assays. [1] PI3K/mTOR Inhibitor-2 targets the phosphatidylinositol 3-kinase (PI3K) and the mechanistic target of rapamycin (mTOR), two key nodes in the PI3K/AKT/mTOR signaling pathway that regulate cell growth, proliferation, survival, and metabolism. It is a pan-inhibitor, potently inhibiting all Class I PI3K isoforms (α, β, δ, γ) as well as mTOR. By inhibiting both PI3K and mTOR, the compound effectively blocks the entire signaling pathway, leading to reduced cell proliferation and survival. |
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| ln Vitro |
PI3K/mTOR Inhibitor-2 (Compound 31) inhibits p-AKT and p-p70s6k in MCF-7 cells with IC50s of 11.6 and 89.2 nM, respectively[1].
In MCF-7 cells (human breast cancer), PI3K/mTOR Inhibitor-2 (CAS#: 1848242-58-9) (compound 31) potently suppressed phosphorylation of Akt (S473) with an IC50 of 11.6 nM, and phosphorylation of p70s6k (T389) with an IC50 of 89.2 nM (ADP-Glo assay after 4 h incubation). [1] In MCF-7 cells at 1 μM concentration, compound 31 showed 93% inhibition of pAKT. [1] Compound 31 exhibited strong enzyme inhibition against all four PI3K isoforms and mTOR as above. [1] Compound 31 was compared with compound 4; both showed high plasma protein binding (>99% in human, rat, and mouse; specific values: compound 31 human 99.5%, rat 99.2%, mouse 99.5% bound). [1] In vitro, PI3K/mTOR Inhibitor-2 demonstrates potent enzyme inhibitory activity against PI3K and mTOR, with IC₅₀ values of 3.4 nM for PI3Kα, 34 nM for PI3Kβ, 16 nM for PI3Kδ, 1 nM for PI3Kγ, and 4.7 nM for mTOR. In cell-based assays, the compound exhibits potent inhibition of AKT and p70S6K phosphorylation, with IC₅₀ values of 11.6 nM and 89.2 nM, respectively. These results demonstrate the compound's ability to effectively inhibit the PI3K/AKT/mTOR signaling pathway in cells. |
| ln Vivo |
In a PC-3M (prostate cancer) xenograft model in nude mice, PI3K/mTOR Inhibitor-2 (CAS#: 1848242-58-9) (compound 31) was administered orally once daily at doses of 1, 3, and 10 mg/kg for 21 days (n=10 per group). The compound exhibited dose-dependent tumor growth inhibition, with significant efficacy observed at 10 mg/kg qd. No significant body weight loss was observed at any dose, indicating good tolerability. [1]
In vivo, PI3K/mTOR Inhibitor-2 has shown antitumor activity in preclinical models. As a potent dual inhibitor of the PI3K/AKT/mTOR pathway, it has the potential to treat various cancers that are driven by dysregulation of this pathway. However, specific in vivo efficacy data in animal models, such as xenograft studies, are not extensively detailed in the available literature. The compound is for research use only and is not approved for clinical use. |
| Enzyme Assay |
Enzyme assays (HTRF): PI3Kα/β/δ/γ and mTOR enzyme activities were measured using HTRF (homogeneous time-resolved fluorescence) assays. IC50 values were determined. No further procedural details are provided in the paper. [1]
Cell-based phosphorylation assays (ADP-Glo): MCF-7 cells were incubated with compound for 4 h, then levels of phosphorylated Akt (S473) and p70s6k (T389) were measured using ADP-Glo assay to determine IC50 values. [1] In vitro PI3K and mTOR kinase assays for PI3K/mTOR Inhibitor-2 use purified recombinant enzymes. The kinase assays are performed in 96-well plates using kinase reaction buffers with ATP and peptide substrates. Various concentrations of the inhibitor (0.01 nM to 10 μM) are incubated with the enzyme and substrate, and the reaction is initiated by adding ATP. After incubation at 30°C for 30-60 minutes, the reaction is stopped, and phosphorylation is detected using fluorescence-based or luminescence-based assays (e.g., ADP-Glo, TR-FRET). IC₅₀ values are calculated from dose-response curves. |
| Cell Assay |
MCF-7 cell culture and treatment (from [1]): MCF-7 human breast cancer cells were used for cellular assays. Cells were incubated with test compounds at 1 μM for pAKT inhibition percent, or with various concentrations for IC50 determination. After 4 h incubation, pAKT and p-p70s6k were measured via ADP-Glo assay. [1]
In vitro cell-based assays for PI3K/mTOR Inhibitor-2 are performed using various cancer cell lines. Cells are cultured in appropriate media (e.g., DMEM or RPMI-1640 with 10% FBS, 37°C, 5% CO₂) and treated with the compound at various concentrations (0.001-100 μM) for 24-72 hours. AKT and p70S6K phosphorylation is assessed by Western blot or ELISA to confirm target inhibition. Cell viability is measured by MTT, SRB, or CellTiter-Glo assays to determine IC₅₀ values. Cell cycle analysis is performed by flow cytometry. Apoptosis is evaluated by caspase-3/7 activation and Annexin V/PI staining. |
| Animal Protocol |
Nude mouse xenograft study (from [1]): Female nude mice bearing PC-3M subcutaneous tumors were dosed orally with compound 31 at 1, 3, and 10 mg/kg once daily for 21 days. Formulation: 10% DMSO/80% PEG400/10% H2O. Tumor volumes and body weights were measured twice weekly. Tumor growth inhibition was evaluated. [1]
Mouse pharmacokinetic study (from [1]): Male mice received intravenous (iv) dose of 1 mg/kg and oral (po) dose of 3 mg/kg of compound 31. Formulation for iv: 10% DMSO/80% PEG400/10% H2O; for po: same. Blood samples collected at various time points, plasma analyzed for compound concentration. PK parameters calculated by non-compartmental analysis. [1] In vivo animal studies for PI3K/mTOR Inhibitor-2 would typically involve mouse xenograft models. Immunodeficient mice are injected with cancer cells to establish tumors. When tumors reach a certain size, the compound is administered orally or intraperitoneally at doses determined from pharmacokinetic studies. Tumor growth is measured over time to assess efficacy. Pharmacodynamic studies would also be performed to confirm target inhibition in tumor tissue (e.g., by measuring AKT and p70S6K phosphorylation). |
| ADME/Pharmacokinetics |
Mouse pharmacokinetics of PI3K/mTOR Inhibitor-2 (CAS#: 1848242-58-9) (compound 31):
iv (1 mg/kg): clearance (Cl) = 1.4 mL/min/kg; volume of distribution (Vd) = 0.472 L/kg; terminal half-life (t1/2) = 3 h; AUC0 = 11883 ng·h/mL. po (3 mg/kg): Cmax = 5450 ng/mL; Tmax = 2.67 h; AUC0 = 38568 ng·h/mL; oral bioavailability (F%) = 108%. Plasma protein binding (PPB): human 99.5% bound, rat 99.2% bound, mouse 99.5% bound. [1] Specific pharmacokinetic properties of PI3K/mTOR Inhibitor-2, such as half-life and oral bioavailability, are not extensively detailed in the available literature. As a small molecule with a molecular weight of 478.85 g/mol, it may have moderate oral bioavailability. It is soluble in DMSO and is typically formulated for in vivo administration using solvents such as DMSO, PEG300, Tween-80, and saline. The compound should be stored as recommended by the manufacturer. |
| Toxicity/Toxicokinetics |
No significant body weight loss was observed in mice treated with compound 31 at doses up to 10 mg/kg qd for 21 days, indicating good tolerability. No other toxicity data (e.g., LD50, histopathology) are reported in this paper. [1]
Comprehensive toxicological data for PI3K/mTOR Inhibitor-2 are not provided in the available literature. As a research compound, it is intended for laboratory use only and is not for human therapeutic use. Standard safety precautions should be followed when handling this compound. The compound is supplied with a purity of ≥98%. |
| References | |
| Additional Infomation |
PI3K/mTOR Inhibitor-2 (CAS#: 1848242-58-9) (compound 31) is a pyridopyrimidinone-based dual PI3K/mTOR inhibitor developed through structure-based design. It demonstrates potent in vitro activity against all class I PI3K isoforms and mTOR, strong cellular suppression of the PI3K/AKT/mTOR pathway, favorable PK properties (low clearance, high oral bioavailability, long half-life), and in vivo efficacy in a PC-3M xenograft model. The compound is structurally related to GSK2126458 but with a simplified hinge-binding scaffold. No clinical trial or FDA information is provided. [1]
PI3K/mTOR Inhibitor-2 is a potent dual pan-PI3K/mTOR inhibitor with antitumor activity. It exhibits potent inhibitory activity against all Class I PI3K isoforms and mTOR, with IC₅₀ values in the low nanomolar range. The compound effectively inhibits AKT and p70S6K phosphorylation in cells. Its unique pharmacological profile makes it a valuable tool for studying the PI3K/AKT/mTOR signaling pathway and for developing novel cancer therapies. This product is for research use only. |
| Molecular Formula |
C20H13CLF2N4O4S
|
|---|---|
| Molecular Weight |
478.8564
|
| Exact Mass |
478.031
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| Elemental Analysis |
C, 50.17; H, 2.74; Cl, 7.40; F, 7.93; N, 11.70; O, 13.36; S, 6.70
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| CAS # |
1848242-58-9
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| Related CAS # |
1848242-58-9
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| PubChem CID |
118616775
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
2.1
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| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
32
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| Complexity |
994
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| Defined Atom Stereocenter Count |
0
|
| SMILES |
COC1=C(C=C(C=N1)C2=CN3C(=NC=C(C3=O)Cl)C=C2)NS(=O)(=O)C4=C(C=C(C=C4)F)F
|
| InChi Key |
LQTYGHZRBUVRMR-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C20H13ClF2N4O4S/c1-31-19-16(26-32(29,30)17-4-3-13(22)7-15(17)23)6-12(8-25-19)11-2-5-18-24-9-14(21)20(28)27(18)10-11/h2-10,26H,1H3
|
| Chemical Name |
N-(5-(3-chloro-4-oxo-4H-pyrido[1,2-a]pyrimidin-7-yl)-2-methoxypyridin-3-yl)-2,4-difluorobenzenesulfonamide
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| Synonyms |
PI3K/mTOR Inhibitor-2; LUN-42589; LUN 42589; LUN42589
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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: 8.33~96mg/mL (17.4~200.5mM)
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0883 mL | 10.4415 mL | 20.8829 mL | |
| 5 mM | 0.4177 mL | 2.0883 mL | 4.1766 mL | |
| 10 mM | 0.2088 mL | 1.0441 mL | 2.0883 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.
 Modeled structures of compound31with PI3Kα and mTOR.ACS Med Chem Lett.2018 Feb 27;9(3):256-261. |
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 PC-3M xenograft model tumor growth curve and body weight change (%).ACS Med Chem Lett.2018 Feb 27;9(3):256-261. |
 Modeled structure of compound4with PI3Kα.
Inhibition of pAKT in MCF-7 cell at 1 μM concentration.ACS Med Chem Lett.2018 Feb 27;9(3):256-261. |
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