PI-103 |
Catalog No.GC11165
One-Click Copy Product Info
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PI-103 is a potent cell-permeable multi-target inhibitor that primarily acts on the PI3K and mTOR signaling pathways.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 371935-74-9
Sample solution is provided at 25 µL, 10mM.
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PI-103 is a potent cell-permeable multi-target inhibitor that primarily acts on the PI3K and mTOR signaling pathways[1]. PI-103 inhibits PI3K subtypes p110α (8nM), p110β (88nM), p110δ (48nM), and p110γ (158nM), as well as mTOR complexes mTORC1 (20nM) and mTORC2 (83nM), while simultaneously inhibiting DNA-PK activity (2nM)[2]. PI-103 can induce mitochondrial apoptosis and autophagy in cells[3]. PI-103 can restore the sensitivity of cancer cells to radiotherapy and chemotherapy[4].
In vitro, pretreatment of Dalton's lymphoma ascites (DLA) cells with PI-103 (10μM) for 24 hours, followed by stimulation with H₂O₂ (1mM) for 30 minutes, significantly inhibited the PI3K-AKT signaling pathway and induced apoptosis, while reducing the accumulation of reactive oxygen species (ROS)[5]. Pretreatment of Huh7 hepatocellular carcinoma cells with PI-103 (2μM) for 1 hour, followed by stimulation with EGF (2.5nM) for 15 minutes, significantly inhibited the phosphorylation of key proteins in the PI3K/AKT/mTOR signaling pathway and blocked EGF-stimulated cell proliferation[6].
In vivo, intraperitoneal injection of PI-103 (10mg/kg) combined with olaparib (10mg/kg) three times per week, used to treat mouse models implanted with MDA-MB-435S cells for 2 weeks followed by radiotherapy (3Gy per fraction), significantly enhanced the inhibitory effect of radiotherapy on triple-negative breast cancer xenografts[7]. Daily intraperitoneal injection of PI-103 (10mg/kg or 70mg/kg) in FVB/N mice for 8 days to several weeks significantly promoted the growth of melanoma xenografts, while inhibiting thymocyte count and inducing immunosuppression[8].
References:
[1] Park S, Chapuis N, Bardet V, et al. PI-103, a dual inhibitor of Class IA phosphatidylinositide 3-kinase and mTOR, has antileukemic activity in AML. Leukemia. 2008 Sep;22(9):1698-706.
[2] Raynaud FI, Eccles SA, Patel S, et al. Biological properties of potent inhibitors of class I phosphatidylinositide 3-kinases: from PI-103 through PI-540, PI-620 to the oral agent GDC-0941. Mol Cancer Ther. 2009 Jul;8(7):1725-38.
[3] Djuzenova CS, Fischer T, Katzer A, et al. Opposite effects of the triple target (DNA-PK/PI3K/mTOR) inhibitor PI-103 on the radiation sensitivity of glioblastoma cell lines proficient and deficient in DNA-PKcs. BMC Cancer. 2021 Nov 11;21(1):1201.
[4] Toulany M, Iida M, Keinath S, et al. Dual targeting of PI3K and MEK enhances the radiation response of K-RAS mutated non-small cell lung cancer. Oncotarget. 2016 Jul 12;7(28):43746-43761.
[5] Maurya AK, Vinayak M. PI-103 attenuates PI3K-AKT signaling and induces apoptosis in murineT-cell lymphoma. Leuk Lymphoma. 2017 May;58(5):1153-1161.
[6] Gedaly R, Angulo P, Hundley J, et al. PI-103 and sorafenib inhibit hepatocellular carcinoma cell proliferation by blocking Ras/Raf/MAPK and PI3K/AKT/mTOR pathways. Anticancer Res. 2010 Dec;30(12):4951-8.
[7] Jang NY, Kim DH, Cho BJ, et al. Radiosensitization with combined use of olaparib and PI-103 in triple-negative breast cancer. BMC Cancer. 2015 Mar 3;15:89.
[8] López-Fauqued M, Gil R, Grueso J, et al. The dual PI3K/mTOR inhibitor PI-103 promotes immunosuppression, in vivo tumor growth and increases survival of sorafenib-treated melanoma cells. Int J Cancer. 2010 Apr 1;126(7):1549-61.
| Cell experiment [1]: | |
Cell lines | Huh7 cells (human hepatocellular carcinoma cell line) |
Preparation Method | Huh7 cells were maintained in Dulbecco's minimal essential medium (DMEM) supplemented with 10% heat-inactivated fetal bovine serum (FBS) at 37°C, 5% CO₂. Cells were treated with PI-103 (2μM) at specified concentrations for designated time periods prior to epidermal growth factor (EGF; 2.5μM) stimulation or irradiation. |
Reaction Conditions | 2μM; 1h pretreatment |
Applications | PI-103 significantly inhibited EGF-stimulated phosphorylation of mTOR (Ser2448, 45% inhibition), S6K (Thr389, 87% inhibition), and AKT (Ser473, 88% inhibition), indicating potent dual inhibition of both mTORC1 and mTORC2 activity. |
| Animal experiment [2]: | |
Animal models | Nude mice |
Preparation Method | Mice were implanted subcutaneously with MDA-MB-435S cells transfected with pGL4 luciferase reporter vector. One week after implantation, mice were treated with intraperitoneal administration of PI-103 (10mg/kg) alone or in combination with Olaparib (10mg/kg) three times weekly for 2 weeks, followed by irradiation (3Gy per fraction, three times weekly). Mice were observed for 2 weeks post-treatment and analyzed via bioluminescence imaging. |
Dosage form | 10mg/kg; i.p. |
Applications | Combined treatment with PI-103 and Olaparib significantly reduced tumor volume compared to radiation alone, demonstrating enhanced radiosensitization in triple-negative breast cancer xenografts. PI-103 alone showed synergistic effects with Olaparib in blocking tumor growth post-irradiation. |
References: | |
| Cas No. | 371935-74-9 | SDF | |
| Chemical Name | 3-(4-morpholin-4-ylpyrido[2,3]furo[2,4-b]pyrimidin-2-yl)phenol | ||
| Canonical SMILES | C1COCCN1C2=NC(=NC3=C2OC4=C3C=CC=N4)C5=CC(=CC=C5)O | ||
| Formula | C19H16N4O3 | M.Wt | 348.36 |
| Solubility | ≥ 21.9mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.8706 mL | 14.353 mL | 28.7059 mL |
| 5 mM | 574.1 μL | 2.8706 mL | 5.7412 mL |
| 10 mM | 287.1 μL | 1.4353 mL | 2.8706 mL |
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 19 reference(s) in Google Scholar.)