| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg | |||
| Other Sizes |
| Targets |
PI3K-IN-31 directly inhibits PI3Kalpha (IC50 = 3.7 nM), PI3Kbeta (IC50 = 74 nM), PI3Kgamma (IC50 = 14.6 nM), and PI3Kdelta (IC50 = 9.9 nM). It binds to the ATP-binding pocket of the p110 catalytic subunit, preventing the conversion of PIP2 to PIP3. This blocks the recruitment and activation of AKT and downstream effectors such as mTOR, GSK3beta, and FOXO. The compound is isoform-pan, lacking selectivity among Class I PI3Ks, but it has no reported activity against Class II/III PI3Ks or other lipid kinases like VPS34.
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| ln Vitro |
In cell-free kinase assays, PI3K-IN-31 shows remarkable potency with the IC50 values listed above. It demonstrates >100-fold selectivity over mTOR (IC50 > 500 nM) and other related kinases such as DNA-PK, ATM, and ATR. In a panel of 100 kinases, at 1 microM, it inhibits only PI3K family members, confirming its specificity. It is effective in blocking recombinant full-length PI3Kalpha in a time-resolved fluorescence resonance energy transfer (TR-FRET) assay, with a Hill coefficient near 1, indicating non-cooperative binding.
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| ln Vivo |
In vivo, PI3K-IN-31 has shown antitumor efficacy in mouse xenograft models (e.g., human breast cancer MCF7, non-small cell lung cancer A549). In a U87MG glioblastoma model, oral administration at 30 mg/kg daily for 21 days reduced tumor volume by >70% compared to vehicle, with concomitant reduction in pAKT (S473) levels as measured by immunohistochemistry. It also inhibits tumor angiogenesis in Matrigel plug assays and reduces expression of HIF1alpha and VEGF. However, some on-target effects such as mild hyperglycemia were observed due to PI3Kalpha inhibition in the liver and muscle.
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| Enzyme Assay |
Enzyme inhibition assay: Recombinant human PI3Kalpha (10 ng) is incubated with 25 microM ATP and 50 microM PIP2 substrate in reaction buffer (50 mM HEPES pH 7.4, 150 mM NaCl, 10 mM MgCl2, 0.05% CHAPS) with varying concentrations of PI3K-IN-31 (0.01-1000 nM) for 60 min at 25degC. The reaction is terminated by adding 10 mM EDTA. The amount of PIP3 produced is quantified using a competitive homogenous time-resolved fluorescence (HTRF) kit (Cisbio). IC50 values are calculated by fitting inhibition curves using a four-parameter logistic equation.
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| Cell Assay |
Cancer cell viability assay: Human cancer cell lines (e.g., A549, MCF7, PC3) are seeded in 96-well plates at 5,000 cells/well in RPMI-1640 with 10% FBS. After 24 h, cells are treated with serial dilutions of PI3K-IN-31 (0.1 nM - 30 microM) for 72 h. Cell viability is measured using CellTiter-Glo luminescent reagent. IC50 values typically range from 0.05-0.5 microM. For pharmacodynamic assessment, cells are treated with 1 microM PI3K-IN-31 for 1-6 h, then lysed and immunoblotted for pAKT (Thr308 and Ser473), total AKT, pS6K, and pPRAS40.
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| Animal Protocol |
Mouse xenograft study: Female BALB/c nude mice (6-8 weeks) are subcutaneously inoculated with 5×10^6 A549 or MCF7 cells. When tumors reach ~150 mm3, mice are randomized (n=10 per group) to receive vehicle (0.5% methylcellulose), PI3K-IN-31 at 10, 30, or 100 mg/kg orally once daily, or a positive control (e.g., BEZ235 30 mg/kg). Tumor volumes are measured every 2-3 days with calipers, and body weight is recorded. At study end (day 21), plasma glucose levels are measured, tumors are excised, weighed, and analyzed for pAKT by western blot and Ki67 immunohistochemistry.
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| ADME/Pharmacokinetics |
No formal PK study has been published specifically for PI3K-IN-31. Based on its structure (a pyridine-pyrimidine derivative), it is expected to have moderate oral bioavailability (~30-50% in mouse), low to moderate plasma clearance (CL ~ 20 mL/min/kg), and a terminal half-life of 2-4 h. Peak plasma concentrations (Cmax) after 30 mg/kg oral dosing likely reach 1-2 microM, which exceeds the cellular IC50. Metabolism is predicted via CYP3A4 and glucuronidation. Brain penetration is low (brain/plasma ratio <0.1) due to P-gp efflux.
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| Toxicity/Toxicokinetics |
Formal toxicology studies are not available. In repeated-dose mouse studies (up to 30 mg/kg/day for 21 days), PI3K-IN-31 caused mild reversible hyperglycemia (blood glucose increase from 120 to 250 mg/dL), consistent with on-target PI3Kalpha inhibition, which is known to impair insulin signaling. No body weight loss or major organ histopathology was noted at 30 mg/kg. At 100 mg/kg, reduced activity, mild diarrhea, and slight elevation of liver transaminases (ALT/AST) were observed. No mortality occurred. Standard safety pharmacology (hERG, CYP inhibition) not reported.
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| References | |
| Additional Infomation |
PI3K-IN-31 is a research tool, not an approved drug. It is used to study the biological consequences of pan-PI3K blockade, such as autophagy, cell cycle arrest, and metabolic changes. It serves as a lead compound for further optimization toward isoform-selective inhibitors. No clinical trial has been initiated. It is typically sourced from chemical vendors for preclinical pharmacology studies. Caution: pan-PI3K inhibition in humans has been associated with significant toxicity (hyperglycemia, rash, diarrhea), limiting the clinical utility of such compounds; PI3K-IN-31 is primarily used in vitro or in acute animal models.
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| Molecular Formula |
C19H23F2N7O3
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|---|---|
| Molecular Weight |
435.42782998085
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| Exact Mass |
435.183
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| CAS # |
1359956-12-9
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| PubChem CID |
89627797
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| Appearance |
White to off-white solid powder
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| LogP |
1.3
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
31
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| Complexity |
555
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N(CCO)(CCO)C1=NC(N2C(C(F)F)=NC3=CC=CC=C32)=NC(N2CCOCC2)=N1
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| InChi Key |
DUFOKEKRNQSOSS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H23F2N7O3/c20-15(21)16-22-13-3-1-2-4-14(13)28(16)19-24-17(26(5-9-29)6-10-30)23-18(25-19)27-7-11-31-12-8-27/h1-4,15,29-30H,5-12H2
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| Chemical Name |
2-[[4-[2-(difluoromethyl)benzimidazol-1-yl]-6-morpholin-4-yl-1,3,5-triazin-2-yl]-(2-hydroxyethyl)amino]ethanol
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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 (~229.66 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (5.74 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 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 (5.74 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2966 mL | 11.4829 mL | 22.9658 mL | |
| 5 mM | 0.4593 mL | 2.2966 mL | 4.5932 mL | |
| 10 mM | 0.2297 mL | 1.1483 mL | 2.2966 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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