| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
PI3Kα 2.3 nM (IC50)
PI3Kalpha (Phosphoinositide 3-kinase alpha). (S)-PI3Kalpha-IN-4 is a selective PI3Kalpha inhibitor with an IC50 of 1.8 nM. By potently and selectively inhibiting the alpha isoform of PI3K, it blocks the production of the second messenger PIP3, preventing the activation of the AKT kinase and downstream pro-survival signaling. The (S)-enantiomer is the active isomer. |
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| ln Vitro |
Compound 11, or (S)-PI3Kα-IN-4, is a derivative of quinazolin-4(3H)-one that substitutes 2-substituted-N-methylpropanamide[1].
In vitro, (S)-PI3Kalpha-IN-4 potently inhibits the activity of the PI3Kalpha kinase with an IC50 of 1.8 nM. It demonstrates selectivity over other Class I PI3K isoforms (PI3Kbeta, gamma, delta). By blocking the PI3K pathway, it inhibits the proliferation of cancer cells, leading to cell cycle arrest and apoptosis. Its activity is identical to the racemate but with defined stereochemistry. |
| ln Vivo |
In vivo, (S)-PI3Kalpha-IN-4 has demonstrated antitumor activity in mouse xenograft models. As an orally active inhibitor, it is a valuable tool for evaluating the effects of sustained PI3Kalpha blockade on tumor growth. Specific efficacy data (e.g., tumor growth inhibition rates) are not provided in the summary, but it is expected to match those of the racemate.
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| Enzyme Assay |
Standard cell‑free binding assays for (S)-PI3Kalpha-IN-4 are performed using recombinant human PI3Kalpha enzyme. The assay is carried out in a 50 mM HEPES buffer (pH 7.5) containing 10 mM MgCl2, 1 mM DTT, and 0.05% CHAPS. The enzyme is incubated with a PIP2 lipid substrate and 10 uM ATP. Varying concentrations of the compound (0.01-1000 nM) are added to the reaction. After 30-60 minutes, the production of PIP3 is measured using a competitive HTRF (homogeneous time-resolved fluorescence) assay. The IC50 is calculated from the inhibition curve and should be 1.8 nM. Selectivity is confirmed by testing the compound against the beta, gamma, and delta isoforms of PI3K.
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| Cell Assay |
A cellular assay for (S)-PI3Kalpha-IN-4 is performed in human cancer cell lines harboring activating PIK3CA mutations, such as MCF7 (breast) or HCT116 (colorectal) cells. Cells are seeded in 96‑well plates (5,000 cells/well) in DMEM/10% FBS. After 24 hours, cells are treated with varying concentrations of the compound (0.1-10000 nM) for 48-72 hours. Cell viability is measured using the CellTiter-Glo luminescence assay. To assess pathway inhibition, cells are treated with the compound for 2-6 hours, and cell lysates are analyzed by Western blot. Blots are probed with antibodies against p-AKT (Ser473) and p-S6K (Thr389). A reduction in these signals indicates effective pathway inhibition. The antiproliferative effect should be more pronounced in PI3Kalpha-mutant cells compared to wild-type or PI3Kbeta-dependent cells.
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| Animal Protocol |
In vivo studies are performed in female athymic nude mice bearing human tumor xenografts with a PIK3CA mutation (e.g., MCF7). Mice (6-8 weeks) are injected subcutaneously with 5×10⁶ cells in Matrigel. When tumors reach an average volume of 150-200 mm3, mice are randomized into treatment groups (n=8-10). (S)-PI3Kalpha-IN-4 is formulated in a vehicle such as 0.5% methylcellulose and administered by oral gavage at doses of 1-30 mg/kg once daily for 2-4 weeks. Tumor volume is measured with calipers every 2-3 days. Body weight is monitored for signs of toxicity. At the end of the study, mice are euthanized, and tumors are excised. Tumor lysates are analyzed by Western blot to confirm the inhibition of the PI3K pathway (p-AKT, p-S6K). Blood is collected for pharmacokinetic analysis of the compound by LC-MS/MS.
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| ADME/Pharmacokinetics |
(S)-PI3Kalpha-IN-4 (MW 560.00, C25H23ClFN5O5S) is an orally active, selective PI3Kalpha inhibitor. It is soluble in DMSO (≥50 mg/mL) and is formulated for oral gavage in research studies. Its pharmacokinetic profile likely includes good oral bioavailability and a half-life suitable for once-daily dosing.
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| Toxicity/Toxicokinetics |
Preclinical toxicity data are not detailed. At the doses used in research (e.g., 10-30 mg/kg), the compound is typically well-tolerated. As a PI3Kalpha inhibitor, potential on-target side effects include hyperglycemia (insulin resistance) and skin rash. These would be monitored in a research setting.
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| References | |
| Additional Infomation |
(S)-PI3Kalpha-IN-4 is a potent and selective inhibitor of PI3Kalpha (IC50 1.8 nM) with antitumor activity. It is the active single enantiomer of PI3Kalpha-IN-4. CAS: 2322293-84-3. It is used for research into the PI3K/AKT pathway in cancer.
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| Molecular Formula |
C25H23CLFN5O5S
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|---|---|
| Molecular Weight |
560.00
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| Exact Mass |
559.109
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| CAS # |
2322293-84-3
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| PubChem CID |
155129768
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| Appearance |
Off-white to yellow solid powder
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| LogP |
2.8
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
38
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| Complexity |
997
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1=CC(=C(C=C1F)Cl)S(NC1=CC(C2=CC=C3C(=C2)C(N(C=N3)C[C@H](C)C(NC)=O)=O)=CN=C1OC)(=O)=O
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| InChi Key |
LPATWVFSBNDSHR-AWEZNQCLSA-N
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| InChi Code |
InChI=1S/C25H23ClFN5O5S/c1-14(23(33)28-2)12-32-13-30-20-6-4-15(8-18(20)25(32)34)16-9-21(24(37-3)29-11-16)31-38(35,36)22-7-5-17(27)10-19(22)26/h4-11,13-14,31H,12H2,1-3H3,(H,28,33)/t14-/m0/s1
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| Chemical Name |
(2S)-3-[6-[5-[(2-chloro-4-fluorophenyl)sulfonylamino]-6-methoxypyridin-3-yl]-4-oxoquinazolin-3-yl]-N,2-dimethylpropanamide
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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: 100 mg/mL (178.57 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.46 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.46 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.46 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7857 mL | 8.9286 mL | 17.8571 mL | |
| 5 mM | 0.3571 mL | 1.7857 mL | 3.5714 mL | |
| 10 mM | 0.1786 mL | 0.8929 mL | 1.7857 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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