- 貨號 Cat. No.
- S2743
- 規格 Size
- 5~200mg
- 品牌 Brand
- Selleckchem
Description
PF-04691502Licensed by Pfizer
PF-04691502 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, little activity against either Vps34, AKT, PDK1, p70S6K, MEK, ERK, p38, or JNK. Phase 2.
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10mM/1mLIn DMSO |
USD 239 |
In stock |
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5mg |
USD 138 |
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10mg |
USD 214 |
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50mg |
USD 718 |
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200mg |
USD 1978 |
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
Description |
PF-04691502 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, little activity against either Vps34, AKT, PDK1, p70S6K, MEK, ERK, p38, or JNK. Phase 2. |
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Targets |
PI3Kα |
PI3Kβ |
PI3Kδ |
PI3Kγ |
mTOR |
Akt |
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IC50 |
1.8 nM (Ki) |
2.1 nM (Ki) |
1.6 nM (Ki) |
1.9 nM (Ki) |
16 nM (Ki) |
7.5 nM/3.8 nM [1] |
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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] |
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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. [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] |
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Features |
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Protocol(Only for Reference)
Kinase Assay: [1]
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. |
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Cell Assay: [1]
Cell lines |
BT20, U87MG, and SKOV3 cells |
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Concentrations |
0-3 mM |
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Incubation Time |
3 days |
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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 |
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Animal Study: [2]
Animal Models |
LSL-KrasG12D heterozygous mice (B6.129-Kras tm4Tyj) and Ptendel mice (c;129S4-Pten tm1Hwu/J), Orthotopic transplant of ovarian tumors |
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Dosages |
daily at either 7.5 or 10 mg/kg |
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Administration |
Administered via oral gavage |
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1
References
Clinical Trial Information( data from http://clinicaltrials.gov)
NCT Number |
Recruitment |
Conditions |
Sponsor
/Collaborators |
Start Date |
Phases |
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NCT00927823 |
Completed |
Cancer |
Pfizer |
2009-12 |
Phase 1 |
NCT01347866 |
Recruiting |
Advanced Cancer |
Pfizer |
2011-10 |
Phase 1 |
NCT01420081 |
Recruiting |
Endometrial Neoplasms |
Pfizer |
2012-01 |
Phase 2 |
NCT01430585 |
Terminated |
Early Breast Cancer (Phase 2)|Advanced Breast Cancer (Phase 1b) |
Pfizer |
2012-03 |
Phase 2 |
NCT01658176 |
Withdrawn |
Breast Neoplasms |
Pfizer |
2013-01 |
Phase 2 |
Download PF-04691502 SDF
Molecular Weight (MW) |
425.48 |
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Formula |
C22H27N5O4
|
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CAS No. |
1013101-36-4 |
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Storage |
3 years -20℃Powder |
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6 months-80℃in DMSO |
Syonnyms |
N/A |
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Solubility (25°C) * |
In vitro |
DMSO |
14 mg/mL (32 mM) |
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Water |
<1 mg/mL (<1 mM) |
Ethanol |
<1 mg/mL (<1 mM) |
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
Chemical Name |
2-amino-8-((1r,4r)-4-(2-hydroxyethoxy)cyclohexyl)-6-(6-methoxypyridin-3-yl)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one |
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Stock Solution (1ml DMSO) |
1mM |
10mM |
20mM |
30mM |
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Mass(mg) |
0.42548 |
4.2548 |
8.5096 |
12.7644 |
Customer Reviews (1)
Click to enlarge |
Rating |
|
Source |
Dr. Zhang of Tianjin Medical University. PF-04691502 purchased from Selleck |
Method |
Western Blot |
Cell Lines |
A549 cells |
Concentrations |
0-10 μM |
Incubation Time |
3 h |
Results |
PF-04691502 treatment resulted in a reduction of AKT phosphorylation. |
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