InformationPF-04691502 (PF4691502) is an ATP-competitivePI3K(α/β/δ/γ)/mTORdual inhibitor withKiof 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 inducesapoptosis.In vitroPF-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.In vivoAntitumor activity of PF-04691502 is observed in U87 (PTEN ), 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.Cell Datacell lines：Concentrations：0-3 mMIncubation Time：3 daysPowder Purity:≥98%. Specification: 10mM in DMSO Molecular Formula: C22H27N5O4 Molecular Weight: 425.48
- UPC:
- 51183703
- Condition:
- New
- Availability:
- 8-12 weeks
- Weight:
- 0.85 Ounces
- HazmatClass:
- No
- WeightUOM:
- LB
- MPN:
- P408101-1ml
- CAS:
- 1013101-36-4
- Product Size:
- 1ml
