| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
mTOR 0.42 nM (IC50) PI3Kα 8 nM (IC50) PI3Kβ 24 nM (IC50) PI3Kγ 74 nM (IC50) PI3Kδ 77 nM (IC50) E545K 14 nM (IC50) H1047R 77 nM (IC50)
PKI-179 hydrochloride targets both phosphoinositide 3-kinase (PI3K) isoforms and the mammalian target of rapamycin (mTOR). It exhibits IC50 values of 8 nM for PI3K-alpha, 24 nM for PI3K-beta, 74 nM for PI3K-gamma, 77 nM for PI3K-delta, and 0.42 nM for mTOR, demonstrating potent inhibition across this key signaling axis. |
|---|---|
| ln Vitro |
PKI-179 reduces the growth of cells, exhibiting IC50 values for MDA361 and PC3 cells of 22 nM and 29 nM, respectively[1]. At dosages up to >30 μM, PKI-179 exhibits inhibitory activity against a panel of 361 different kinases, hERG, and cytochrome P450 (CYP) isoforms; nevertheless, it does exhibit activity for CYP2C8 (IC50=3 μM)[1].
A typical in vitro kinase inhibition assay is performed using purified recombinant PI3K isoforms (alpha, beta, gamma, delta) and mTOR kinase. Increasing concentrations of PKI-179 hydrochloride are incubated with the respective kinase, ATP, and a substrate (PIP2 for PI3K or a specific peptide for mTOR). The amount of phosphorylated product is measured to calculate the respective IC50 values for each target. |
| ln Vivo |
In nude mice bearing MDA-361 human breast cancer tumors, PKI-179 (5-50 mg/kg; po once daily for 40 days) reduces the tumor growth and is well tolerated[1]. Good suppression of PI3K signaling is observed in nude mice containing MDA361 tumor xenografts when PKI-179 (50 mg/kg; po) is administered[1]. PKI-179 has a high half-life (>60 min) and good oral bioavailability (98% in naked mouse, 46% in rat, 38% in monkey, and 61% in dog)[1].
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| Cell Assay |
PKI-179 hydrochloride can be evaluated in various cancer cell lines (e.g., PC-3 prostate, MCF-7 breast). Cells are seeded in 96-well plates and treated with a 10-point dilution series of the compound (0.1 nM to 10 uM) for 72 hours. Cell viability is then determined using a CellTiter-Glo luminescent assay. For mechanism confirmation, cells are treated for 2-6 hours, lysed, and analyzed by Western blot for p-AKT (S473), p-S6, and p-4E-BP1 levels.
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| Animal Protocol |
Animal/Disease Models: Nude mice bearing MDA-361 human breast cancer tumors[1]
Doses: 5, 10, 25, 50 mg/kg Route of Administration: Ip every 3 days for 4 weeks Experimental Results: demonstrated pronounced tumor growth arrest when dosed above 10 mg/kg. No significant weight loss of tested animals was observed for all different dosages. PKI-179 hydrochloride shows anti-tumor activity in vivo. A typical xenograft model involves subcutaneous implantation of cancer cells (e.g., U87MG glioblastoma) into nude mice. When tumors reach ~100-200 mm3, mice are orally dosed daily with PKI-179 hydrochloride (e.g., 10-50 mg/kg). Tumor volumes are measured bi-weekly for 3-4 weeks to calculate TGI, with endpoints including immunohistochemistry for p-S6 and p-AKT to confirm target modulation. |
| ADME/Pharmacokinetics |
As an orally active compound, PKI-179 hydrochloride is designed for convenient dosing. Based on its chemical properties, it likely exhibits moderate to high oral bioavailability and a suitable half-life for once- or twice-daily administration. Specific PK parameters are not detailed in the provided references.
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| Toxicity/Toxicokinetics |
No specific toxicology data is reported for PKI-179 hydrochloride. As a PI3K/mTOR dual inhibitor, potential class-related toxicities may include metabolic disturbances, rash, and gastrointestinal effects, which are typically evaluated in GLP toxicology studies for clinical candidates.
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| References |
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| Additional Infomation |
PKI-179 hydrochloride (CAS: 1463510-35-1) is a potent and orally active dual PI3K/mTOR inhibitor. It has IC50s of 8 nM (PI3K-alpha), 24 nM (PI3K-beta), 74 nM (PI3K-gamma), 77 nM (PI3K-delta), and 0.42 nM (mTOR). It also inhibits PI3Kalpha mutants E545K and H1047R. This compound is a valuable pharmacological tool for studying the PI3K/AKT/mTOR pathway and evaluating therapeutic strategies in oncology drug discovery.
|
| Molecular Formula |
C25H29CLN8O3
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|---|---|
| Molecular Weight |
525.002563238144
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| Exact Mass |
524.205
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| CAS # |
1463510-35-1
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| Related CAS # |
PKI-179;1197160-28-3
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| PubChem CID |
137699924
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
37
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| Complexity |
714
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N(C1C=CC(C2N=C(N3CCOCC3)N=C(N3C4COCC3CC4)N=2)=CC=1)C(=O)NC1=CC=NC=C1.Cl
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| InChi Key |
JNMURGIZAFELTR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H28N8O3.ClH/c34-25(28-19-7-9-26-10-8-19)27-18-3-1-17(2-4-18)22-29-23(32-11-13-35-14-12-32)31-24(30-22)33-20-5-6-21(33)16-36-15-20;/h1-4,7-10,20-21H,5-6,11-16H2,(H2,26,27,28,34);1H
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| Chemical Name |
1-[4-[4-morpholin-4-yl-6-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-1,3,5-triazin-2-yl]phenyl]-3-pyridin-4-ylurea;hydrochloride
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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: 20 mg/mL (38.10 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (2.38 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 12.5 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. Solubility in Formulation 2: ≥ 1.25 mg/mL (2.38 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 12.5 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 | 1.9048 mL | 9.5238 mL | 19.0476 mL | |
| 5 mM | 0.3810 mL | 1.9048 mL | 3.8095 mL | |
| 10 mM | 0.1905 mL | 0.9524 mL | 1.9048 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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