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Sonolisib (also known as PX-866)is a novel, oral, irreversible, and pan-isoform small-molecule inhibitor of phosphoinositide 3-kinase/PI3K with potential anticancer activity (IC50=0.1 nM (p110α), 1.0 nM (p120γ), and 2.9 nM (p110δ). anti-tumor effects. Sonolisib prevents the secondary messenger phosphatidylinositol-3,4,5-triphosphate (PIP3) from being produced and the PI3K/Akt signaling pathway from being activated, which may prevent the growth and survival of tumor cells in populations of tumor cells that are susceptible to this effect. The PI3K/Akt signaling pathway is frequently involved in the development of tumors, and aberrant PI3K/Akt signaling may play a role in the development of tumor resistance to a range of antineoplastic agents.
Physicochemical Properties
| Molecular Formula | C29H35NO8 |
| Molecular Weight | 525.5901 |
| Exact Mass | 525.236 |
| Elemental Analysis | C, 66.27; H, 6.71; N, 2.66; O, 24.35 |
| CAS # | 502632-66-8 |
| Related CAS # | 502632-66-8 |
| PubChem CID | 9849735 |
| Appearance | Yellow solid powder |
| Density | 1.3±0.1 g/cm3 |
| Boiling Point | 651.4±55.0 °C at 760 mmHg |
| Flash Point | 347.7±31.5 °C |
| Vapour Pressure | 0.0±4.4 mmHg at 25°C |
| Index of Refraction | 1.586 |
| LogP | 2.37 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 9 |
| Rotatable Bond Count | 9 |
| Heavy Atom Count | 38 |
| 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 |
| 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 |
| Synonyms | Sonolisib; PX 866; PX866; PX866 |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| Targets | p110α (IC50 = 0.1 nM); p110δ (IC50 = 2.9 nM); p120γ (IC50 = 1 nM) |
| 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]. |
| References |
[1]. The phosphatidylinositol-3-kinase inhibitor PX-866 overcomes resistance to the epidermal growthfactor receptor inhibitor ZD1839 in A-549 human non-small cell lung cancer xenografts. Mol Cancer Ther. 2005 Sep;4(9):1349-57. [2]. A Randomized, Phase II Trial of C225 With or Without PX-866, an Irreversible Oral Phosphatidylinositol 3-Kinase Inhibitor, in Patients With Metastatic Colorectal Carcinoma. Clin Colorectal Cancer. 2016 Dec;15(4):337-344.e2. [3]. Sonolisib. |
| Additional Infomation |
PX-866 is an organic heterotetracyclic compound that is obtained from wortmanin via aminolysis of its furan ring by diallyl amine. It has a role as an EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor. It is an organic heterotetracyclic compound, a delta-lactone, an acetate ester and a tertiary amino compound. It is functionally related to a wortmannin. Sonolisib has been used in trials studying the treatment of Glioblastoma, Prostate Cancer, Advanced Solid Tumors, Advanced BRAF-mutant Cancers, and Non Small Cell Lung Cancer (NSCLC), among others. Sonolisib is a small-molecule wortmannin analogue inhibitor of the alpha, gamma, and delta isoforms of phosphoinositide 3-kinase (PI3K) with potential antineoplastic activity. Sonolisib inhibits the production of the secondary messenger phosphatidylinositol-3,4,5-trisphosphate (PIP3) and activation of the PI3K/Akt signaling pathway, which may result in inhibition of tumor cell growth and survival in susceptible tumor cell populations. Activation of the PI3K/Akt signaling pathway is frequently associated with tumorigenesis and dysregulated PI3K/Akt signaling may contribute to tumor resistance to a variety of antineoplastic agents. |
Solubility Data
| Solubility (In Vitro) | DMSO: ~100 mg/mL (190.3 mM) |
| 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 |