| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
p110α (IC50 = 0.1 nM); p110δ (IC50 = 2.9 nM); p120γ (IC50 = 1 nM)
Sonolisib targets the PI3K family of kinases, specifically the α, γ, and δ isoforms. It exhibits IC50 values of 0.1 nM for p110α, 1.0 nM for p120γ, and 2.9 nM for p110δ. By irreversibly inhibiting these isoforms, it blocks the production of phosphatidylinositol-3,4,5-trisphosphate (PIP3) and downstream activation of the PI3K/Akt signaling pathway. |
|---|---|
| ln Vitro |
Sonolisib (PX-866) suppresses the activation of PI3K/Akt signaling and the phospholipid messenger phosphoinositol-3,4,5-trisphosphate (PIP3), which may suppress the proliferation of tumor cells and vulnerable tumor cell populations [3].
In vitro, Sonolisib inhibits the production of the secondary messenger phosphatidylinositol-3,4,5-trisphosphate and suppresses activation of the PI3K/Akt signaling pathway. This leads to inhibition of tumor cell growth and survival in susceptible tumor cell populations. The compound demonstrates potent antiproliferative effects against cancer cell lines with aberrant PI3K/Akt signaling. |
| ln Vivo |
In vivo, Sonolisib has demonstrated antitumor activity in preclinical models and has been evaluated in clinical trials for multiple cancer indications. As an orally bioavailable agent, it has shown the ability to inhibit tumor growth in susceptible populations by suppressing PI3K/Akt pathway activation.
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| Enzyme Assay |
The in vitro enzyme assay typically uses recombinant PI3K isoforms (p110α/p110δ/p120γ) and measures the inhibition of kinase activity. The compound is incubated with the enzyme, ATP, and a substrate such as phosphatidylinositol-4,5-bisphosphate (PIP2). The production of PIP3 is quantified using a homogeneous time-resolved fluorescence (HTRF) or luminescent assay to determine the IC50 values.
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| Cell Assay |
For in vitro cellular assays, cancer cell lines with activated PI3K/Akt signaling are cultured in appropriate media and treated with Sonolisib at varying concentrations (typically 0.001-10 μM) for 48-72 hours. Cell viability is assessed using MTT or CellTiter-Glo assays. Additionally, Western blotting is performed to measure the phosphorylation levels of Akt (Ser473) and other downstream effectors to confirm pathway inhibition.
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| Animal Protocol |
In vivo, Sonolisib is typically administered orally to tumor-bearing immunocompromised mice at doses ranging from 1-10 mg/kg daily or on a scheduled basis. Tumor volume is measured periodically using calipers, and body weight is monitored for toxicity. At study termination, tumors are harvested for Western blot analysis of PI3K/Akt pathway biomarkers and immunohistochemical assessment of proliferation (Ki-67) and apoptosis (cleaved caspase-3).
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| ADME/Pharmacokinetics |
Sonolisib is orally bioavailable with favorable pharmacokinetic properties suitable for once-daily dosing. As a small-molecule inhibitor (molecular weight 525.59), it shows good systemic exposure following oral administration. The compound is typically formulated in vehicles such as DMSO/PEG300/Tween 80/saline for in vivo studies.
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| Toxicity/Toxicokinetics |
Preclinical toxicity studies have shown that Sonolisib is generally well-tolerated at therapeutic doses, with expected toxicities related to PI3K pathway inhibition including metabolic disturbances and potential gastrointestinal effects. In clinical trials, adverse events have been manageable. The compound has undergone Phase I/II evaluation in multiple solid tumors.
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| References |
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| Additional Infomation |
PX-866 is an organic heterotetracyclic compound derived from waultmannin via diallylamine ammonolysis of the furan ring. It is an EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor. It is an organic heterotetracyclic compound with a δ-lactone, acetate, and tertiary amine structure. Its function is related to that of waultmannin. Sonnorib has been used in clinical trials for the treatment of various cancers, including glioblastoma, prostate cancer, advanced solid tumors, advanced BRAF-mutant cancers, and non-small cell lung cancer (NSCLC). Sonnorib is a small-molecule waultmannin analog that inhibits the α, γ, and δ isoforms of phosphatidylinositol 3-kinase (PI3K), exhibiting potential antitumor activity. Sonnorib inhibits the production of the second messenger phosphatidylinositol-3,4,5-triphosphate (PIP3) and the activation of the PI3K/Akt signaling pathway, which may lead to the suppression of the growth and survival of susceptible tumor cell populations. Activation of the PI3K/Akt signaling pathway is often associated with tumorigenesis, while dysregulation of the PI3K/Akt signaling pathway may lead to tumor resistance to multiple antitumor drugs.
Sonolisib (PX-866) is a wortmannin analog developed as a second-generation PI3K inhibitor with improved stability and oral bioavailability compared to wortmannin. It acts by covalently binding to the kinase domain of PI3K isoforms, providing irreversible inhibition. Clinical trials have explored its use as monotherapy and in combination with other agents such as docetaxel for advanced solid tumors, glioblastoma, and BRAF-mutant cancers. It has not received regulatory approval for clinical use. |
| Molecular Formula |
C29H35NO8
|
|---|---|
| Molecular Weight |
525.5901
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| Exact Mass |
525.236
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| Elemental Analysis |
C, 66.27; H, 6.71; N, 2.66; O, 24.35
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| CAS # |
502632-66-8
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| Related CAS # |
502632-66-8
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| PubChem CID |
9849735
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| Appearance |
Yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
651.4±55.0 °C at 760 mmHg
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| Flash Point |
347.7±31.5 °C
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| Vapour Pressure |
0.0±4.4 mmHg at 25°C
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| Index of Refraction |
1.586
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| LogP |
2.37
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
9
|
| Heavy Atom Count |
38
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| Complexity |
1200
|
| Defined Atom Stereocenter Count |
5
|
| SMILES |
C=CCN(CC=C)/C=C\1/C2=C(C(=O)C3=C(C(CC4(C)C3CCC4=O)OC(=O)C)C2(C)C(COC)OC1=O)O
|
| InChi Key |
QIUASFSNWYMDFS-NILGECQDSA-N
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| InChi Code |
InChI=1S/C29H35NO8/c1-7-11-30(12-8-2)14-17-23-26(34)25(33)22-18-9-10-20(32)28(18,4)13-19(37-16(3)31)24(22)29(23,5)21(15-36-6)38-27(17)35/h7-8,14,18-19,21,34H,1-2,9-13,15H2,3-6H3/b17-14+/t18-,19+,21+,28-,29-/m0/s1
|
| Chemical Name |
(4S,4aR,5R,6aS,9aR,E)-1-((diallylamino)methylene)-11-hydroxy-4-(methoxymethyl)-4a,6a-dimethyl-2,7,10-trioxo-1,2,4,4a,5,6,6a,7,8,9,9a,10-dodecahydroindeno[4,5-h]isochromen-5-yl acetate
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| Synonyms |
Sonolisib; PX 866; PX866; PX866
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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 (190.3 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.76 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 (4.76 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9026 mL | 9.5131 mL | 19.0262 mL | |
| 5 mM | 0.3805 mL | 1.9026 mL | 3.8052 mL | |
| 10 mM | 0.1903 mL | 0.9513 mL | 1.9026 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.
| NCT Number | Status | Interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01408316 | Completed | Drug: PX-866 | Healthy Volunteer | Cascadian Therapeutics Inc. | July 2011 | Phase 1 |
| NCT00726583 | Completed | Drug: PX-866 | Advanced Solid Tumors | Cascadian Therapeutics Inc. | June 2008 | Phase 1 |
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