PF-04691502
Based on 11 publication(s) in Google Scholar
PF-04691502 is a potent and selective inhibitor of PI3K and mTOR. PF-04691502 binds to human PI3Kα, β, δ, γ and mTOR with Kis of 1.8, 2.1, 1.6, 1.9 and 16 nM, respectively.
Nos produits utilisent uniquement pour la recherche. Nous ne vendons pas aux patients.
- Pureté: 99.33%
- CAS No.: 1013101-36-4
- Formule: C22H27N5O4
- Masse moléculaire:425.48
-
Stockage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 1 year , -20°C, 6 months
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
-
Activité biologique
-
Chemical Information
-
Solvant et solubilité
- Protocole
- Pureté et documentation
- Références
-
Help & FAQs
Publications Citing Use of MedChemExpress (MCE) PF-04691502
More- Sci Transl Med. 2018 Jul 18;10(450):eaaq1093. [Abstract]
- Theranostics. 2020 Jan 1;10(4):1531-1543. [Abstract]
- Acta Pharm Sin B. 2022 Jul;12(7):3139-3155. [Abstract]
- Cell Death Differ. 2021 Jul;28(7):2221-2237. [Abstract]
- Cell Death Dis. 2022 Apr 21;13(4):387. [Abstract]
- J Med Chem. 2026 Feb 12;69(3):3519-3536. [Abstract]
- Cells. 2025 Sep 21;14(18):1474. [Abstract]
- Front Pharmacol. 2020 Nov 11:11:580407. [Abstract]
- Molecules. 2020 Apr 23;25(8):1980. [Abstract]
- bioRxiv. 2023 Feb 8.
- bioRxiv. 2020 Jun.
Activité biologique
|
PI3Kδ 1.6 nM (Ki) |
PI3Kα 1.8 nM (Ki) |
PI3Kγ 1.9 nM (Ki) |
PI3Kβ 2.1 nM (Ki) |
mTOR 16 nM (Ki) |
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| BT-20 | IC50 |
13 nM
Compound: 1, PF-04691502
|
Inhibition of AKT phosphorylation at S473 in human BT20 cells after 1 hr by sandwich ELISA
Inhibition of AKT phosphorylation at S473 in human BT20 cells after 1 hr by sandwich ELISA
|
10.1039/C0MD00072H |
| BT-20 | IC50 |
13 nM
Compound: PF-04691502
|
Inhibition of AKT phosphorylation at Ser 473 in human BT20 cells
Inhibition of AKT phosphorylation at Ser 473 in human BT20 cells
|
[PMID: 23506825] |
| NCI-H460 | IC50 |
0.2 μM
Compound: 1; PF-04691502
|
Cytotoxicity against human NCI-H460 cells after 96 hrs by MTT assay
Cytotoxicity against human NCI-H460 cells after 96 hrs by MTT assay
|
[PMID: 29927604] |
| SK-OV-3 | IC50 |
0.29 μM
Compound: PF-04691502
|
Antiproliferative activity against human SKOV3 cells after 3 days by CellTiter-Glo assay
Antiproliferative activity against human SKOV3 cells after 3 days by CellTiter-Glo assay
|
[PMID: 25139570] |
| SK-OV-3 | IC50 |
7.4 nM
Compound: 1, PF-04691502
|
Inhibition of AKT phosphorylation at S473 in human SKOV3 cells after 1 hr by sandwich ELISA
Inhibition of AKT phosphorylation at S473 in human SKOV3 cells after 1 hr by sandwich ELISA
|
10.1039/C0MD00072H |
| U-87MG ATCC | IC50 |
0.34 μM
Compound: PF-04691502
|
Antiproliferative activity against human U87MG cells after 4 days by Celltiter-Glo luminescence cell viability assay
Antiproliferative activity against human U87MG cells after 4 days by Celltiter-Glo luminescence cell viability assay
|
[PMID: 29305298] |
| U-87MG ATCC | IC50 |
0.52 μM
Compound: PF-04691502
|
Antiproliferative activity against human U87MG cells after 4 days by CellTiter-Glo assay
Antiproliferative activity against human U87MG cells after 4 days by CellTiter-Glo assay
|
[PMID: 25139570] |
PF-04691502 inhibits recombinant mouse PI3Kα in an ATP-competitive inhibitor. PF-04691502 potently inhibits AKT phosphorylation on S473 and T308 in all the 3 cancer cell lines with IC50 values of 3.8 to 20 nM and 7.5 to 47 nM, respectively. Using a 96-well plate-based P-S6RP(S235/236) ELISA assay, PF-04691502 potently inhibits mTORC1 activity with an IC50 of 32 nM. PF-04691502 inhibits cell proliferation of BT20, SKOV3, and U87MG with IC50 values of 313, 188, and 179 nM, respectively. In PIK3CA-mutant and PTEN-deleted cancer cell lines, PF-04691502 reduces phosphorylation of AKT T308 and AKT S473 (IC50 of 7.5-47 nM and 3.8-20 nM, respectively) and inhibits cell proliferation (IC50 of 179-313 nM). PF-04691502 inhibits mTORC1 activity in cells as measured by PI3K-independent nutrient stimulated assay, with an IC50 of 32 nM and inhibits the activation of PI3K and mTOR downstream effectors including AKT, FKHRL1, PRAS40, p70S6K, 4EBP1, and S6RP[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| NCT Number | Sponsor | Condition | Start Date |
Phase
|
|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
-
CAS No. 1013101-36-4
-
Appearance Solid
-
Masse moléculaire 425.48
-
Formule C22H27N5O4
-
Color Off-white to gray
-
SMILES
OCCO[C@@H]1CC[C@@H](N2C(N=C(N)N=C3C)=C3C=C(C4=CC=C(OC)N=C4)C2=O)CC1
-
Livraison
Room temperature in continental US; may vary elsewhere.
-
Stockage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 1 year -20°C 6 months
Publications (11)
-
Journal Impact Factor
-
Most Recent
-
Sci Transl Med
PP2A inhibition is a druggable MEK inhibitor resistance mechanism in KRAS-mutant lung cancer cells. [Abstract]2018 Jul 18;10(450):eaaq1093. PMID: 30021885 -
Theranostics
Response to mTOR and PI3K inhibitors in enzalutamide-resistant luminal androgen receptor triple-negative breast cancer patient-derived xenografts. [Abstract]2020 Jan 1;10(4):1531-1543. PMID: 32042320 -
Acta Pharm Sin B
Engineering prodrug nanomicelles as pyroptosis inducer for codelivery of PI3K/mTOR and CDK inhibitors to enhance antitumor immunity. [Abstract]2022 Jul;12(7):3139-3155. PMID: 35865097 -
Cell Death Differ
Constitutive GLI1 expression in chondrosarcoma is regulated by major vault protein via mTOR/S6K1 signaling cascade. [Abstract]2021 Jul;28(7):2221-2237. PMID: 33637972 -
Cell Death Dis
HGF/c-Met pathway facilitates the perineural invasion of pancreatic cancer by activating the mTOR/NGF axis. [Abstract]2022 Apr 21;13(4):387. PMID: 35449152 -
J Med Chem
Revitalizing PI3K Inhibitors for PET/CT Imaging and Radionuclide Therapy of Multiple Cancers. [Abstract]2026 Feb 12;69(3):3519-3536. PMID: 41593021 -
Cells
PF-04691502, a PI3K/mTOR Dual Inhibitor, Ameliorates AD-like Pathology in a Mouse Model of AD. [Abstract]2025 Sep 21;14(18):1474. PMID: 41002439 -
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 -
Molecules
In Vitro and in Vivo Activity of mTOR Kinase and PI3K Inhibitors Against Leishmania donovani and Trypanosoma brucei. [Abstract]2020 Apr 23;25(8):1980. PMID: 32340370 -
-
Solvant et solubilité
DMSO : 50 mg/mL (117.51 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
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, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.
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, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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 (5.88 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 (5.88 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:
-
-
-
-
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
-
%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
-
%+
-
+%Tween-80 + +
-
%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.
Protocole
The biochemical protein kinase assays for class I PI3K and mTOR are assessed. The fluorescence polarization assay for ATP competitive inhibition is done as follows: mPI3Kα dilution solution (90 nM) is prepared in fresh assay buffer (50 mM Hepes pH 7.4, 150 mM NaCl, 5 mM DTT, 0.05% CHAPS) and kept on ice. The enzyme reaction contained 0.5 nM mouse PI3Kα (p110α/p85α complex purified from insect cells), 30 μM PIP2, PF-04691502 (0, 1, 4, and 8 nM), 5 mM MgCl2, and 2-fold serial dilutions of ATP (0-800 μM). Final DMSO is 2.5%. The reaction is initiated by the addition of ATP and terminated after 30 minutes with 10 mM EDTA. In a detection plate, 15 uL of detector/probe mixture containing 480 nM GST-Grp1PH domain and 12 nM TAMRA tagged fluorescent PIP3 in assay buffer is mixed with 15 uL of kinase reaction mixture. The plate is shaken for 3 minutes, and incubated for 35 to 40 minutes before reading on an LJL Analyst HT[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
BT20, U87MG, and SKOV3 cells are plated at 3,000 cell/well in 96-well culture plates in growth medium with 10% FBS. Cells are incubated overnight and treated with DMSO (0.1% final) or serial diluted compound for 3 days. Resazurin is added to 0.1 mg/mL. Plates are incubated at 37°C in 5% CO2 for 3 hours. Fluorescence signals are read as emission at 590 nm after excitation at 530 nm. IC50 values are calculated by plotting fluorescence intensity to drug concentration in nonlinear curves. U87MG and SKOV3 cells are plated in 96-well plates overnight and caspase-3/caspase-7 activity is assessed with the Caspase-Glo 3/7 Assay Kit[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Mice[1]
Female nu/nu mice (6-8 weeks old) are used. Tumor cells for implantation are harvested and resuspended in serum-free medium mixed with matrigel (1:1). SKOV3, U87MG, or NSCLC cells (2.5-4×106) are implanted subcutaneously into the hind flank region. Treatment started when average tumor size is 100 to 200 mm3. PF-04691502 is formulated in 0.5% methylcellulose in water suspension and given orally once a day. Animal body weights and tumor volumes are measured every 2 to 3 days. Tumor volume is determined with Vernier calipers and calculated. Percentage of tumor growth inhibition (TGI) is calculated. Data are presented as mean±SE. Comparisons between treatment groups and vehicle group are done using 1-way ANOVA by Dunnett's tests. Student's t test is used to determine the P value for the comparison of 2 groups.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Pureté et documentation
-
Fiche technique (283 KB)
-
SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
-
Instruction de manipulation (2659 KB)
Références
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, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.3503 mL | 11.7514 mL | 23.5029 mL | 58.7572 mL |
| 5 mM | 0.4701 mL | 2.3503 mL | 4.7006 mL | 11.7514 mL | |
| 10 mM | 0.2350 mL | 1.1751 mL | 2.3503 mL | 5.8757 mL | |
| 15 mM | 0.1567 mL | 0.7834 mL | 1.5669 mL | 3.9171 mL | |
| 20 mM | 0.1175 mL | 0.5876 mL | 1.1751 mL | 2.9379 mL | |
| 25 mM | 0.0940 mL | 0.4701 mL | 0.9401 mL | 2.3503 mL | |
| 30 mM | 0.0783 mL | 0.3917 mL | 0.7834 mL | 1.9586 mL | |
| 40 mM | 0.0588 mL | 0.2938 mL | 0.5876 mL | 1.4689 mL | |
| 50 mM | 0.0470 mL | 0.2350 mL | 0.4701 mL | 1.1751 mL | |
| 60 mM | 0.0392 mL | 0.1959 mL | 0.3917 mL | 0.9793 mL | |
| 80 mM | 0.0294 mL | 0.1469 mL | 0.2938 mL | 0.7345 mL | |
| 100 mM | 0.0235 mL | 0.1175 mL | 0.2350 mL | 0.5876 mL |
PF-04691502 Related Classifications
HY-15177 Related Classifications
Powered by Bioz