Bimiralisib
Based on 4 publication(s) in Google Scholar
Bimiralisib (PQR309) 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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- 純度: 98.62%
- CAS 番号: 1225037-39-7
- 分子式: C17H20F3N7O2
- 分子量:411.38
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保管条件:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
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生物活性
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化学情報
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溶剤 & 溶解度
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MedChemExpress（MCE）の使用を引用している文献 Bimiralisib
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生物活性
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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) |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| A2058 | IC50 |
139 nM
Compound: 1; PQR309
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Inhibition of mTORC2 in human A2058 cells assessed as reduction in PKB phosphorylation at S473 residues incubated for 1 hr by Western blot analysis
Inhibition of mTORC2 in human A2058 cells assessed as reduction in PKB phosphorylation at S473 residues incubated for 1 hr by Western blot analysis
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[PMID: 31465220] |
| A2058 | IC50 |
139 nM
Compound: 5; PQR309
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Inhibition of Class 1 PI3K/mTOR in human A2058 cells assessed as reduction in Akt phosphorylation at Ser473 residue incubated for 1 hr by InCell Western assay
Inhibition of Class 1 PI3K/mTOR in human A2058 cells assessed as reduction in Akt phosphorylation at Ser473 residue incubated for 1 hr by InCell Western assay
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[PMID: 31244112] |
| A2058 | IC50 |
205 nM
Compound: 1; PQR309
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Inhibition of mTORC1 in human A2058 cells assessed as reduction in ribosomal protein S6 phosphorylation at Ser235/236 residues incubated for 1 hr by Western blot analysis
Inhibition of mTORC1 in human A2058 cells assessed as reduction in ribosomal protein S6 phosphorylation at Ser235/236 residues incubated for 1 hr by Western blot analysis
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[PMID: 31465220] |
| A2058 | IC50 |
205 nM
Compound: 5; PQR309
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Inhibition of Class 1 PI3K/mTOR in human A2058 cells assessed as reduction in S6 phosphorylation at Ser235/236 residue incubated for 1 hr by InCell Western assay
Inhibition of Class 1 PI3K/mTOR in human A2058 cells assessed as reduction in S6 phosphorylation at Ser235/236 residue incubated for 1 hr by InCell Western assay
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[PMID: 31244112] |
| A2058 | IC50 |
2333 nM
Compound: 1; PQR309
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Antiproliferative activity against human A2058 cells after 48 hrs by sulforhodamine B assay
Antiproliferative activity against human A2058 cells after 48 hrs by sulforhodamine B assay
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[PMID: 28829592] |
| SK-OV-3 | IC50 |
237 nM
Compound: 1; PQR309
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Antiproliferative activity against human SKOV3 cells after 48 hrs by sulforhodamine B assay
Antiproliferative activity against human SKOV3 cells after 48 hrs by sulforhodamine B assay
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[PMID: 28829592] |
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].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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[1].
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[1].
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].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
化学情報
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CAS 番号 1225037-39-7
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性状 Solid
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分子量 411.38
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分子式 C17H20F3N7O2
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Color White to gray
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SMILES
NC1=NC=C(C2=NC(N3CCOCC3)=NC(N4CCOCC4)=N2)C(C(F)(F)F)=C1
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別名
PQR309
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Publications (4)
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Journal Impact Factor
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Most Recent
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Leukemia
BET inhibitor-based combinations targeting novel dependencies in MECOM-rearranged (r) AML. [Abstract]2025 Dec 19. PMID: 41419608 -
Int J Mol Sci
Rationale for Combining the BCL2 Inhibitor Venetoclax with the PI3K Inhibitor Bimiralisib in the Treatment of IDH2- and FLT3-Mutated Acute Myeloid Leukemia. [Abstract]2022 Oct 20;23(20):12587. PMID: 36293442 -
Front Pharmacol
CC-223, NSC781406, and BGT226 Exerts a Cytotoxic Effect Against Pancreatic Cancer Cells via mTOR Signaling. [Abstract]2020 Nov 11;11:580407. PMID: 33343350 -
Eur J Immunol
Fibroblast transdifferentiation promotes conversion of M1 macrophages and replenishment of cardiac resident macrophages following cardiac injury in mice. [Abstract]2020 Jun;50(6):795-808. PMID: 32068249
溶剤 & 溶解度
DMSO : ≥ 50 mg/mL (121.54 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (6.08 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (6.08 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
プロトコル
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].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
純度とドキュメンテーション
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データシート (283 KB)
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SDS (394 KB)
- English - EN (394 KB)
- Français - FR (394 KB)
- Deutsch - DE (394 KB)
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取扱説明書 (2659 KB)
参考文献
[1]. Beaufils F, et al. 5-(4,6-Dimorpholino-1,3,5-triazin-2-yl)-4-(trifluoromethyl)pyridin-2-amine (PQR309), a Potent, Brain-Penetrant, Orally Bioavailable, Pan-Class I PI3K/mTOR Inhibitor as Clinical Candidate in Oncology. J Med Chem. 2017 Sep 14;60(17):7524-7538. [Content Brief]
[2]. Wicki A, et al. First-in human, phase 1, dose-escalation pharmacokinetic and pharmacodynamic study of the oral dual PI3K and mTORC1/2 inhibitor PQR309 in patients with advanced solid tumors (SAKK 67/13). Eur J Cancer. 2018 Jun;96:6-16. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.4308 mL | 12.1542 mL | 24.3084 mL | 60.7711 mL |
| 5 mM | 0.4862 mL | 2.4308 mL | 4.8617 mL | 12.1542 mL | |
| 10 mM | 0.2431 mL | 1.2154 mL | 2.4308 mL | 6.0771 mL | |
| 15 mM | 0.1621 mL | 0.8103 mL | 1.6206 mL | 4.0514 mL | |
| 20 mM | 0.1215 mL | 0.6077 mL | 1.2154 mL | 3.0386 mL | |
| 25 mM | 0.0972 mL | 0.4862 mL | 0.9723 mL | 2.4308 mL | |
| 30 mM | 0.0810 mL | 0.4051 mL | 0.8103 mL | 2.0257 mL | |
| 40 mM | 0.0608 mL | 0.3039 mL | 0.6077 mL | 1.5193 mL | |
| 50 mM | 0.0486 mL | 0.2431 mL | 0.4862 mL | 1.2154 mL | |
| 60 mM | 0.0405 mL | 0.2026 mL | 0.4051 mL | 1.0129 mL | |
| 80 mM | 0.0304 mL | 0.1519 mL | 0.3039 mL | 0.7596 mL | |
| 100 mM | 0.0243 mL | 0.1215 mL | 0.2431 mL | 0.6077 mL |
Bimiralisib 関連分類
HY-12868 関連分類
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