Home PI3K/Akt/mTOR PI3K inhibitor - Akt inhibitor - mTOR inhibitor - Apoptosis related activator PF-04691502 For research use only.

PF-04691502

Synonyms: PF4691502

PF-04691502 (PF4691502) is an ATP-competitive PI3K(α/β/δ/γ)/mTOR dual inhibitor with Ki of 1.8 nM/2.1 nM/1.6 nM/1.9 nM and 16 nM in cell-free assays, little activity against either Vps34, AKT, PDK1, p70S6K, MEK, ERK, p38, or JNK. PF-04691502 induces apoptosis. Phase 2.

PF-04691502 Chemical Structure

PF-04691502 Chemical Structure

CAS No. 1013101-36-4

Purity & Quality Control

PF-04691502 Related Products

Signaling Pathway

PI3K Signaling Pathways

PI3K Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human BT20 cells Function assay Inhibition of AKT phosphorylation at Ser 473 in human BT20 cells, IC50=0.013 μM 23506825
human SKOV3 cells Proliferation assay 3 days Antiproliferative activity against human SKOV3 cells after 3 days by CellTiter-Glo assay, IC50=0.29 μM 25139570
human U87MG cells Proliferation assay 4 days Antiproliferative activity against human U87MG cells after 4 days by CellTiter-Glo assay, IC50=0.52 μM 25139570
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Biological Activity

Description PF-04691502 (PF4691502) is an ATP-competitive PI3K(α/β/δ/γ)/mTOR dual inhibitor with Ki of 1.8 nM/2.1 nM/1.6 nM/1.9 nM and 16 nM in cell-free assays, little activity against either Vps34, AKT, PDK1, p70S6K, MEK, ERK, p38, or JNK. PF-04691502 induces apoptosis. Phase 2.
Targets
PI3Kδ [1]
(Cell-free assay)		 PI3Kα [1]
(Cell-free assay)		 PI3Kγ [1]
(Cell-free assay)		 PI3Kβ [1]
(Cell-free assay)		 P-Akt (S473) [1]
(Cell-free assay)		 Click to View More Targets
1.6 nM(Ki) 1.8 nM(Ki) 1.9 nM(Ki) 2.1 nM(Ki) 3.8 nM
In vitro
In vitro

PF-04691502 potently inhibits recombinant class I PI3K and mTOR in biochemical assays and suppresses transformation of avian fibroblasts mediated by wild-type PI3K γ, δ, or mutant PI3Kα. In PIK3CA-mutant and PTEN-deleted cancer cell lines, PF-04691502 reduces phosphorylation of AKT T308 and AKT S473 (IC(50) of 7.5-47 nM and 3.8-20 nM, respectively) and inhibits cell proliferation (IC(50) of 179-313 nM). PF-04691502 inhibits mTORC1 activity in cells as measured by PI3K-independent nutrient stimulated assay, with an IC(50) of 32 nM and inhibits the activation of PI3K and mTOR downstream effectors including AKT, FKHRL1, PRAS40, p70S6K, 4EBP1, and S6RP. Short-term exposure to PF-04691502 predominantly inhibits PI3K, whereas mTOR inhibition persists for 24 to 48 hours. PF-04691502 induces cell cycle G(1) arrest, concomitant with upregulation of p27 Kip1 and reduction of Rb. [1]
Kinase Assay Kinase Assay
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 contains 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 dimethyl sulfoxide 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.
Cell Research Cell lines BT20, U87MG, and SKOV3 cells
Concentrations 0-3 mM
Incubation Time 3 days
Method

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 curve
Experimental Result Images Methods Biomarkers Images PMID
Western blot p-AKT / p-ERK p-S6 / S6 23826249
Growth inhibition assay Cell viability 28029662
In Vivo
In vivo

Antitumor activity of PF-04691502 is observed in U87 (PTEN null), SKOV3 (PIK3CA mutation), and non-small cell lung carcinoma xenografts. [1] PF-04691502 inhibits tumor growth at 7 days by 72%. FDG-PET imaging revealed that PF-04691502 reduces glucose metabolism dramatically. Tissue biomarkers of PI3K/mTOR pathway activity, p-AKT (S473), and p-RPS6 (S240/244), are also dramatically inhibited following PF-04691502 treatment. [2]
Animal Research Animal Models LSL-KrasG12D heterozygous mice (B6.129-Kras tm4Tyj) and Ptendel mice (c;129S4-Pten tm1Hwu/J), Orthotopic transplant of ovarian tumors
Dosages daily at either 7.5 or 10 mg/kg
Administration Administered via oral gavage
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01658176 Withdrawn
Breast Neoplasms
Pfizer
 January 2013 Phase 2
NCT01420081 Terminated
Endometrial Neoplasms
Pfizer
 January 19 2012 Phase 2
NCT01347866 Terminated
Advanced Cancer
Pfizer
 October 2011 Phase 1

Chemical Information & Solubility

Molecular Weight 425.48 Formula

C22H27N5O4
CAS No. 1013101-36-4 SDF Download PF-04691502 SDF
Smiles CC1=C2C=C(C(=O)N(C2=NC(=N1)N)C3CCC(CC3)OCCO)C4=CN=C(C=C4)OC
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 14 mg/mL ( (32.9 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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