PF-04691502

SKU: orb1300936

Description

PF-04691502

Research Area

Cell Biology, Signal Transduction

Key Properties

• CAS Number: 1013101-36-4
• MW: 425.48
• Purity: 98.63%
• Formula: C₂₂H₂₇N₅O₄
• SMILES: COc1ccc(cn1)-c1cc2c(C)nc(N)nc2n([C@H]2CC[C@@H](CC2)OCCO)c1=O
• Target: mTOR,Autophagy,Akt,PI3K
• Solubility: DMSO:61.25 mg/mL (143.96 mM);Ethanol:< 1 mg/mL (insoluble or slightly soluble);H2O:< 1 mg/mL (insoluble or slightly soluble);10% DMSO+40% PEG300+5% Tween 80+45% Saline:1 mg/mL (2.35 mM)

Bioactivity

• Target IC50:
  PI3Kδ:1.6 nM(Ki)|PI3Kα:1.8 nM(Ki)|pAkt (S473):3.8 nM|PI3Kβ:2.1 nM(Ki)|mTOR:16 nM (Ki)|PI3Kγ:1.9 nM(Ki)
• In Vivo:
  Antitumor activity of PF-04691502 is observed in U87 (PTEN null), SKOV3 (PIK3CA mutation), and gefitinib- and erlotinib-resistant non-small cell lung carcinoma xenografts. 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.
• 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.
• Cell Research:
  BT20, U87 mg, 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(Only for Reference)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Mammalian target of Rapamycin, Inhibitor, mTOR, inhibit, P-Akt (S473), Autophagy, PF4691502, PF-4691502, PF04691502, PF-04691502, PF 04691502, PF 4691502, PI3Kδ, PI3Kγ, PI3K, PI3Kβ, PI3Kα, Phosphoinositide 3-kinase

Compound Identifiers

PubChem CID

25033539