Physicochemical Properties
| Molecular Formula | C27H21N7 |
| Molecular Weight | 443.50 |
| Exact Mass | 443.185 |
| CAS # | 2845104-25-6 |
| PubChem CID | 168295564 |
| Appearance | Off-white to gray solid powder |
| Density | 1.34±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted) |
| LogP | 4.3 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 34 |
| Complexity | 791 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | JDUUUKXVZOZLSS-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C27H21N7/c1-16-33-23-14-30-22-6-4-17(19-10-18-8-9-29-26(18)32-12-19)11-21(22)25(23)34(16)20-5-7-24(31-13-20)27(2,3)15-28/h4-14H,1-3H3,(H,29,32) |
| Chemical Name | 2-methyl-2-[5-[2-methyl-8-(1H-pyrrolo[2,3-b]pyridin-5-yl)imidazo[4,5-c]quinolin-1-yl]pyridin-2-yl]propanenitrile |
| 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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 | PI3Kα 3.5 nM (IC50) PI3Kδ 4.6 nM (IC50) mTOR 21.3 nM (IC50) |
| ln Vitro | PI3K/mTOR Inhibitor-11 (compound 8o) has been shown to decrease the viability of several human cancer cell lines, including HT29, HCT15, H3122, HeLa, SW620, and H446. Its IC50 values are 0.25, 0.17, 0.29, 0.09, 0.16, and 0.97 μM, respectively[1]. HeLa and SW620 cell colony formation rates are reduced by PI3K/mTOR Inhibitor-11 (0-1.25 μM, 15 days)[1]. HeLa and SW620 cells are arrested at the G0/G1 phases by PI3K/mTOR Inhibitor-11 (0-2.5 μM, 24 h)[1]. In HeLa cells, phosphorylated AKT and S6 proteins are suppressed by PI3K/mTOR Inhibitor-11 (0-2.5 μM, 24 h)[1]. |
| ln Vivo | Compound 8o, administered intragastrically at doses of 15–60 mg/kg, inhibits the growth of HeLa and SW620 xenograft cancers[1]. Oral bioavailability (76.81%) is demonstrated with PI3K/mTOR Inhibitor-11 (1 mg/kg for iv, 10 mg/kg for po, rats)[1]. |
| Cell Assay |
Apoptosis Analysis[1] Cell Types: HeLa and SW620 cells Tested Concentrations: 0, 0.15625, 0.625, 1.25 μM Incubation Duration: 24 h Experimental Results: Affected HeLa cells' apoptosis rate from 6.10 to 66.04% in a dose-dependent manner. Western Blot Analysis[1] Cell Types: HeLa Tested Concentrations: 0 , 0.15625, 0.625, 1.25, 2.5 μM Incubation Duration: 24 h Experimental Results: Suppressed the phosphorylated AKT (Ser473 and Thr308) and S6 proteins. |
| Animal Protocol |
Animal/Disease Models: HeLa and SW620 xenograft models of female BALB/c nude mice[1]. Doses: 15, 30, and 60 mg/kg Route of Administration: intragastric (po) administration, daily for 30 days. Experimental Results: The TGIs (tumor growth inhibitions): 80.22, 73.50, and 60.79% in the HeLa xenograft model at doses of 60, 30, and 15 mg/kg, respectively. TGIs: 81.03, 70.81, and 60.58% in the SW620 xenograft model at doses of 60, 30, and 15 mg/kg, respectively. Animal/Disease Models: Rats[1]. Doses: 1 mg/kg for iv, 10 mg/kg for po Route of Administration: iv, po Experimental Results: pharmacokinetic/PK parameters of PI3K/mTOR Inhibitor-11 (compound 8o) dose (mg/kg) T1/2 (h) Cmax (ng/mL) CL (mL/min/kg) F (%) 1 (iv) 17.2 10 (po) 2.6 2995 76.81% |
| References |
[1]. Discovery of 2-Methyl-2-(4-(2-methyl-8-(1H-pyrrolo[2,3-b]pyridin-6-yl)-1H-naphtho[1,2-d]imidazol-1-yl)phenyl)propanenitrile as a Novel PI3K/mTOR Inhibitor with Enhanced Antitumor Efficacy In Vitro and In Vivo. J Med Chem. 2022 Oct 13;65(19):12781-12801. |
Solubility Data
| Solubility (In Vitro) | DMSO: 40 mg/mL (90.19 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 4 mg/mL (9.02 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 40.0 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 | 2.2548 mL | 11.2740 mL | 22.5479 mL | |
| 5 mM | 0.4510 mL | 2.2548 mL | 4.5096 mL | |
| 10 mM | 0.2255 mL | 1.1274 mL | 2.2548 mL |