Physicochemical Properties
| Molecular Formula | C25H30N6O5 |
| Molecular Weight | 494.552 |
| Exact Mass | 494.227 |
| CAS # | 1375469-38-7 |
| PubChem CID | 135905473 |
| Appearance | White to off-white solid powder |
| Density | 1.4±0.1 g/cm3 |
| Index of Refraction | 1.683 |
| LogP | -0.2 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 7 |
| Heavy Atom Count | 36 |
| Complexity | 1010 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | O1CCN(CC1)C[C@@H](COC1C=CC2C(C=1OC)=N/C(=N\C(C1=CC=CN=C1C)=O)/N1CCNC1=2)O |
| InChi Key | QJTLLKKDFGPDPF-QGZVFWFLSA-N |
| InChi Code | InChI=1S/C25H30N6O5/c1-16-18(4-3-7-26-16)24(33)29-25-28-21-19(23-27-8-9-31(23)25)5-6-20(22(21)34-2)36-15-17(32)14-30-10-12-35-13-11-30/h3-7,17,27,32H,8-15H2,1-2H3/t17-/m1/s1 |
| Chemical Name | N-[8-[(2R)-2-hydroxy-3-morpholin-4-ylpropoxy]-7-methoxy-2,3-dihydro-1H-imidazo[1,2-c]quinazolin-5-ylidene]-2-methylpyridine-3-carboxamide |
| Synonyms | BAY10-82439 BAY-10-82439 BAY 10-82439 |
| 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
| ln Vitro | BAY1082439 is a highly selective PI3Kα/α balance inhibitor. BAY1082439 exhibits an IC50 ratio of 1:3 in PI3Kα (4.9 nM) versus PI3Kα (15.0 nM) biochemical studies and is over 1000-fold selective for mTOR kinase [1]. BAY1082439 (0.1-1 μM; 72 hours) effectively inhibits PTEN-deficient prostate cancer cells, surpassing specific inhibitors of PI3Kα and/or PI3Kβ [2]. |
| ln Vivo | The oral medication BAY1082439 (75 mg/kg; once daily for 4 weeks) is useful in stopping the progression of prostate cancer that lacks PTEN [2]. |
| Cell Assay |
Cell viability assay[2] Cell Types: PC3 and LNCaP cells (PTEN-deleted human prostate cancer cell line) Tested Concentrations: 0.1, 0.33, 1, 3.3, 10 μM Incubation Duration: 72 hrs (hours) Experimental Results: Effective inhibition of cell growth by blocking G1 /S cell cycle transition and by inducing apoptosis. |
| Animal Protocol |
Animal/Disease Models: Pten conditional knockout mouse model (Pb-Cre+; PtenL/L, CP model) [2] Doses: 75 mg/kg Route of Administration: Po; one time/day for 4 weeks Experimental Results: Tumor size and P- AKT staining was Dramatically diminished, the luminal structure was close to normal, and Ki67-positive cells were Dramatically diminished. Dramatically inhibits the growth of human prostate cancer. |
| References |
[1]. Abstract 2799: BAY 1082439, a highly selective and balanced PI3Kα/β inhibitor demonstrated potent activity in tumors with activated PI3Kα and loss-of-function of PTEN. Abstract nr 2799. doi:1538-7445.AM2012-2799. [2]. Co-Targeting the Cell Intrinsic and Microenvironment Pathways of Prostate Cancer by PI3Kα/β/δ inhibitor BAY1082439. Mol Cancer Ther. 2018 Oct;17(10):2091-2099. |
| Additional Infomation | PI3K Alpha/Beta Inhibitor BAY1082439 is an orally bioavailable inhibitor of the class I phosphoinositide 3-kinase (PI3K) alpha and beta isoforms with potential antineoplastic activity. PI3K alpha/beta inhibitor BAY1082439 selectively inhibits both PI3K alpha, including mutated forms of PIK3CA, and PI3K beta in the PI3K/Akt/mTOR pathway, which may result in tumor cell apoptosis and growth inhibition in PI3K-expressing and/or PTEN-driven tumor cells. By specifically targeting class I PI3K alpha and beta, this agent may be more efficacious and less toxic than pan PI3K inhibitors. Dysregulation of the PI3K/Akt/mTOR pathway is frequently found in solid tumors and results in increased tumor cell growth, survival, and resistance to chemotherapy and radiotherapy. PIK3CA, one of the most highly mutated oncogenes, encodes the p110-alpha catalytic subunit of the class I PI3K. PTEN, a tumor suppressor protein and negative regulator of PI3K activity, is often mutated in a variety of cancer cells. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~5 mg/mL (~10.11 mM) |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0220 mL | 10.1102 mL | 20.2204 mL | |
| 5 mM | 0.4044 mL | 2.0220 mL | 4.0441 mL | |
| 10 mM | 0.2022 mL | 1.0110 mL | 2.0220 mL |