PQR-309
Modify Date: 2024-01-08 12:52:02
PQR-309 structure
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Common Name | PQR-309 | ||
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| CAS Number | 1225037-39-7 | Molecular Weight | 411.382 | |
| Density | 1.6±0.1 g/cm3 | Boiling Point | 513.0±60.0 °C at 760 mmHg | |
| Molecular Formula | C17H20F3N7O2 | Melting Point | N/A | |
| MSDS | N/A | Flash Point | 264.0±32.9 °C | |
Use of PQR-309Bimiralisib is a potent, brain-penetrant, orally bioavailable, pan-class I PI3K/mTOR inhibitor with IC50s of 33 nM, 451 nM, 661 nM, 708 nM and 89 nM for PI3Kα, PI3Kδ, PI3Kβ, PI3Kγ and mTOR, respectively. Bimiralisib is an mTORC1 and mTORC2 inhibitor. |
| Name | 5-[4,6-Di(4-morpholinyl)-1,3,5-triazin-2-yl]-4-(trifluoromethyl)-2(1H)-pyridinimine |
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| Synonym | More Synonyms |
| Description | Bimiralisib is a potent, brain-penetrant, orally bioavailable, pan-class I PI3K/mTOR inhibitor with IC50s of 33 nM, 451 nM, 661 nM, 708 nM and 89 nM for PI3Kα, PI3Kδ, PI3Kβ, PI3Kγ and mTOR, respectively. Bimiralisib is an mTORC1 and mTORC2 inhibitor. |
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| Related Catalog | |
| Target |
PI3Kα:33 nM (IC50) PI3Kα-H1047R:36 nM (IC50) PI3Kα-E542K:63 nM (IC50) PI3Kα-E545K:136 nM (IC50) PI3Kδ:451 nM (IC50) PI3Kβ:661 nM (IC50) PI3Kγ:708 nM (IC50) Vps34:6486 nM (IC50) mTOR:89 nM (IC50) mTORC1 mTORC2 DNA-PK:8567 nM (IC50) |
| In Vitro | Bimiralisib is a highly selective pan-PI3K inhibitor with a balanced targeting of mTOR kinase. Bimiralisib also inhibits PI3Kα-H1047R), PI3Kα-E542K and PI3Kα-E545K with IC50s of 36 nM, 63 nM and 136 nM, respectively[1]. |
| In Vivo | Oral administration yields similar concentrations of Bimiralisib in brain and plasma samples illustrates that Bimiralisib readily passes the blood–brain barrier. In mice, both po and iv application routes show a rapid drop below 200 ng/mL (~0.5 μM) of PQR309 within <1 h (iv) to <2 h (po) after administration, which reflects the time point when the drug reaches the median GI50 determined in tumor cell lines. In female rats a single oral dose (10 mg/kg) achieves similar drug levels as a single intravenous injection (5 mg/kg) with regard to Cmax. The half-life of 5-8 h and an AUC0.25-12 of around 14 000 h•ng/mL contributed to an excellent oral bioavailability of PQR309 (>50%). Twenty-four hours after po administration, plasma levels of PQR309 are still >2 μM (800-1000 ng/mL). Moreover, after 1-2 h exposure to PQR309 , drug levels in rat brain samples are comparable to plasma levels, confirming rapid access of PQR309 to the brain[1]. |
| Cell Assay | Human tumor cell lines are seeded into 96-well microtiter plates and exposed to five (1/2 log serial) drug dilutions plus control, followed by 48 h (except for two controls of each cell line which are fixed with TCA (cell population at t =0 h [Tz]). The assay is terminated by fixation with TCA (10% final). Cell density is determined using a sulforhodamine B staining protocol and the absorbance measured at 515 nm. Using seven absorbance measurements, the percentage growth is calculated at each of the drug concentrations levels. Percentage growth inhibition is calculated. The NTRC Oncolines 44 cell lines are exposed for 72 h to 9-point 3-fold serial dilutions of Bimiralisib. The concentration of 50% growth inhibition is associated with the signal ((luminescenceuntreated,t=72h-luminescencet=0)/2)+luminescencet=0. The data set integrated here is used for IC50 calculations. IC50 values of A2058 or SKOV3 cell proliferation given are determined and calculated[1]. |
| Animal Admin | Mice[1] Healthy male nude NIH rats are used. 2×107 PC-3 cells are injected subcutaneously at day 0 (D0) in 200 μL of RPMI1640 into the right flank of male nude rats, 24 h after a whole-body irradiation with a γ-source (5 Gy, 60Co). Tumor-bearing rats are randomized on day 16 (mean volume of 330±70 mm3 according to their individual tumor volume into five groups of each eight animals using Vivo manager software. Analysis of variance is performed to test for homogeneity between groups. Daily administration on D17-D44 and from D51 to D57: group 1, vehicle; group 2, compound 1 at 5 mg/kg; group 3, Bimiralisib at 10 mg/kg. Group 4: Bimiralisib at 15 mg/kg from D17 to D21, from D24 to D28, from D34 to D38, from D41 to D4, and from D51 to D56. Group 5: one iv injection of Vinorelbine at 2.5 mg/kg on D17, D24, D31, and D38. Final termination of rats is performed on D87. Body weight is measured at least twice a week. Length and width of tumors are measured and recorded twice a week with calipers, and the tumor volume is estimated. |
| References |
| Density | 1.6±0.1 g/cm3 |
|---|---|
| Boiling Point | 513.0±60.0 °C at 760 mmHg |
| Molecular Formula | C17H20F3N7O2 |
| Molecular Weight | 411.382 |
| Flash Point | 264.0±32.9 °C |
| Exact Mass | 411.163055 |
| LogP | -1.45 |
| Appearance of Characters | white solid |
| Vapour Pressure | 0.0±1.3 mmHg at 25°C |
| Index of Refraction | 1.669 |
| Storage condition | -20℃ |
| 5-[4,6-Di(4-morpholinyl)-1,3,5-triazin-2-yl]-4-(trifluoromethyl)-2(1H)-pyridinimine |
| 2(1H)-Pyridinimine, 5-(4,6-di-4-morpholinyl-1,3,5-triazin-2-yl)-4-(trifluoromethyl)- |
| PQR-309 |
| PQR309 |