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PF-04691502 PI3K inhibitor

Name: PF-04691502
Brand: Selleck Chemicals
SKU: S2743
Availability: InStock
Rating: 5 (50 reviews)

Cat.No.S2743

PF-04691502 (PF4691502) is an ATP-competitive PI3K(α/β/δ/γ)/mTOR dual inhibitor with K_i 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. This compound induces apoptosis. Phase 2.

Chemical Structure

Molecular Weight: 425.48

Jump to Mechanism of Action Cell Culture & Working Concentration Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: Purity: 99.96%

99.96

Related Targets	Akt mTOR AMPK GSK-3 ATM/ATR DNA-PK PDPK1 PTEN PP2A PDK PI4K PIKfyve MELK
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Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Incubation Time	Activity Description
human BT20 cells	Function assay		Inhibition of AKT phosphorylation at Ser 473 in human BT20 cells, IC50=0.013 μM
human SKOV3 cells	Proliferation assay	3 days	Antiproliferative activity against human SKOV3 cells after 3 days by CellTiter-Glo assay, IC50=0.29 μM
human U87MG cells	Proliferation assay	4 days	Antiproliferative activity against human U87MG cells after 4 days by CellTiter-Glo assay, IC50=0.52 μM
Click to View More Cell Line Experimental Data

Chemical Information, Storage & Stability

Molecular Weight	425.48	Formula	C₂₂H₂₇N₅O₄	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	1013101-36-4	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	PF4691502			Smiles	CC1=C2C=C(C(=O)N(C2=NC(=N1)N)C3CCC(CC3)OCCO)C4=CN=C(C=C4)OC

Solubility

In vitro
Batch:

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

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.600mg/ml (1.41mM)	Taking the 1 mL working solution as an example, add 50 μL of 12 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.600mg/ml (1.41mM)	Taking the 1 mL working solution as an example, add 50 μL of 12 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

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 ddH₂O, 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.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Targets/IC₅₀/Ki	PI3Kδ ^[1] (Cell-free assay) 1.6 nM(Ki) PI3Kα ^[1] (Cell-free assay) 1.8 nM(Ki) PI3Kγ ^[1] (Cell-free assay) 1.9 nM(Ki) PI3Kβ ^[1] (Cell-free assay) 2.1 nM(Ki) P-Akt (S473) ^[1] (Cell-free assay) 3.8 nM P-Akt (T308) ^[1] (Cell-free assay) 7.5 nM mTOR ^[1] (Cell-free assay) 16 nM(Ki)
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, this compound 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). It 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 this chemical predominantly inhibits PI3K, whereas mTOR inhibition persists for 24 to 48 hours. This compound induces cell cycle G(1) arrest, concomitant with upregulation of p27 Kip1 and reduction of Rb. ^[1]
Kinase Assay	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.
In vivo	Antitumor activity of PF-04691502 is observed in U87 (PTEN null), SKOV3 (PIK3CA mutation), and non-small cell lung carcinoma xenografts. ^[1] This compound inhibits tumor growth at 7 days by 72%. FDG-PET imaging revealed that it reduces glucose metabolism dramatically. Tissue biomarkers of PI3K/mTOR pathway activity, p-AKT (S473), and p-RPS6 (S240/244), are also dramatically inhibited following its treatment. ^[2]
References	https://pubmed.ncbi.nlm.nih.gov/21750219/ https://pubmed.ncbi.nlm.nih.gov/21632463/ https://pubmed.ncbi.nlm.nih.gov/22684718/

Applications

Methods	Biomarkers	Images	PMID
Western blot	p-AKT / p-ERK p-S6 / S6		23826249
Growth inhibition assay	Cell viability		28029662

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

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

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