ZSTK474
Based on 18 publication(s) in Google Scholar
ZSTK474 is an ATP-competitive pan-class I PI3K inhibitor with IC50s of 16 nM, 44 nM, 4.6 nM and 49 nM for PΙ3Κα, PI3Kβ, PI3Kδ and PI3Kγ, respectively.
연구목적의 판매만을 진행합니다. 환자를 대상으로 한 판매는 하지 않습니다.
- Purity: 99.71%
- CAS No.: 475110-96-4
- 화학식: C19H21F2N7O2
- 분자량:417.41
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보관:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
Publications Citing Use of MedChemExpress (MCE) ZSTK474
More- Sci Transl Med. 2018 Jul 18;10(450):eaaq1093. [Abstract]
- J Exp Clin Cancer Res. 2018 Jun 25;37(1):122. [Abstract]
- Cell Death Dis. 2026 Jun 23. [Abstract]
- Clin Cancer Res. 2014 Nov 1;20(21):5483-95. [Abstract]
- Neurotherapeutics. 2025 Nov 7:e00769. [Abstract]
- Mol Metab. 2023 May:71:101705. [Abstract]
- J Endocrinol. 2020 Feb;244(2):285-296. [Abstract]
- Molecules. 2020 Apr 23;25(8):1980. [Abstract]
- BMC Cancer. 2024 Jul 26;24(1):902. [Abstract]
- J Biol Chem. 2012 Mar 23;287(13):9742-9752. [Abstract]
- Gene. 2024 Nov 15:927:148649. [Abstract]
- Exp Ther Med. 2022 Jun;23(6):413. [Abstract]
- Meat and Muscle Biology. 2026.
- bioRxiv. 2024 September 07.
- Université de Lausanne. 2024 Feb 7.
- Bioengineered. 2021 Dec;12(2):11847-11857. [Abstract]
- bioRxiv. 2020 Mar.
- Research Square Preprint. 2020 Feb.
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WB
Biological Activity
|
PI3Kδ 4.6 nM (IC50) |
PI3Kα 16 nM (IC50) |
PI3Kβ 44 nM (IC50) |
PI3Kγ 49 nM (IC50) |
Autophagy |
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| A549 | IC50 |
17 nM
Compound: ZSTK474
|
Inhibition of PI3K p110 beta in human A549 cell lysate preincubated with compound for 5 mins followed by [gamma-32p]-ATP addition measured after 20 mins by immunoprecipitation based liquid scintillation spectroscopic analysis
Inhibition of PI3K p110 beta in human A549 cell lysate preincubated with compound for 5 mins followed by [gamma-32p]-ATP addition measured after 20 mins by immunoprecipitation based liquid scintillation spectroscopic analysis
|
[PMID: 16622124] |
| A549 | IC50 |
37 nM
Compound: ZSTK474
|
Inhibition of PI3K in human A549 cell lysate preincubated with compound for 5 mins followed by [gamma-32p]-ATP addition measured after 20 mins by immunoprecipitation based liquid scintillation spectroscopic analysis
Inhibition of PI3K in human A549 cell lysate preincubated with compound for 5 mins followed by [gamma-32p]-ATP addition measured after 20 mins by immunoprecipitation based liquid scintillation spectroscopic analysis
|
[PMID: 16622124] |
| A549 | IC50 |
53 nM
Compound: ZSTK474
|
Inhibition of PI3K p110 gamma in human A549 cell lysate preincubated with compound for 5 mins followed by [gamma-32p]-ATP addition measured after 20 mins by immunoprecipitation based liquid scintillation spectroscopic analysis
Inhibition of PI3K p110 gamma in human A549 cell lysate preincubated with compound for 5 mins followed by [gamma-32p]-ATP addition measured after 20 mins by immunoprecipitation based liquid scintillation spectroscopic analysis
|
[PMID: 16622124] |
| A549 | IC50 |
6 nM
Compound: ZSTK474
|
Inhibition of PI3K p110 delta in human A549 cell lysate preincubated with compound for 5 mins followed by [gamma-32p]-ATP addition measured after 20 mins by immunoprecipitation based liquid scintillation spectroscopic analysis
Inhibition of PI3K p110 delta in human A549 cell lysate preincubated with compound for 5 mins followed by [gamma-32p]-ATP addition measured after 20 mins by immunoprecipitation based liquid scintillation spectroscopic analysis
|
[PMID: 16622124] |
| HCT-116 | IC50 |
0.71 μM
Compound: IV; ZSTK-474
|
Antiproliferative activity against human HCT-116 cells assessed as inhibition of cell proliferation incubated for 96 hrs by MTT assay
Antiproliferative activity against human HCT-116 cells assessed as inhibition of cell proliferation incubated for 96 hrs by MTT assay
|
[PMID: 37736169] |
| HCT-116 | IC50 |
1.31 μM
Compound: ZSTK474
|
Antiproliferative activity against human HCT116 cells harboring PI3Kalpha H1047R mutant after 72 hrs by CCK8 assay
Antiproliferative activity against human HCT116 cells harboring PI3Kalpha H1047R mutant after 72 hrs by CCK8 assay
|
[PMID: 30071408] |
| HCT-116 | IC50 |
1.31 μM
Compound: ZSTK474
|
Antiproliferative activity against human HCT116 cells after 72 hrs by CCK-8 assay
Antiproliferative activity against human HCT116 cells after 72 hrs by CCK-8 assay
|
[PMID: 30245395] |
| HCT-116 | IC50 |
78 nM
Compound: 1, ZSTK474
|
Inhibition of PIK3CA H1047R mutant-mediated cell signaling in human HCT116 cells expressing PTEN assessed as inhibition of insulin-induced pAkt/PKB phosphorylation at Thr308 treated for 15 mins before insulin challenge measured after 5 mins by immunoblott
Inhibition of PIK3CA H1047R mutant-mediated cell signaling in human HCT116 cells expressing PTEN assessed as inhibition of insulin-induced pAkt/PKB phosphorylation at Thr308 treated for 15 mins before insulin challenge measured after 5 mins by immunoblott
|
[PMID: 21882832] |
| HCT-116 | IC50 |
97 nM
Compound: 1, ZSTK474
|
Inhibition of PIK3CA H1047R mutant-mediated cell signaling in human HCT116 cells expressing PTEN assessed as inhibition of insulin-induced pAkt/PKB phosphorylation at Ser473 treated for 15 mins before insulin challenge measured after 5 mins by immunoblott
Inhibition of PIK3CA H1047R mutant-mediated cell signaling in human HCT116 cells expressing PTEN assessed as inhibition of insulin-induced pAkt/PKB phosphorylation at Ser473 treated for 15 mins before insulin challenge measured after 5 mins by immunoblott
|
[PMID: 21882832] |
| HT-29 | GI50 |
300 nM
Compound: ZSTK474
|
Antiproliferative activity against human HT-29 cells incubated for 3 days by WST8 assay
Antiproliferative activity against human HT-29 cells incubated for 3 days by WST8 assay
|
[PMID: 33284613] |
| LNCaP | IC50 |
210 nM
Compound: 6
|
Antiproliferative activity against human LNCAP cells after 3 days by MTS assay
Antiproliferative activity against human LNCAP cells after 3 days by MTS assay
|
[PMID: 20227881] |
| MCF7 | IC50 |
5.27 μM
Compound: ZSTK474
|
Antiproliferative activity against human MCF7 cells after 72 hrs by CCK8 assay
Antiproliferative activity against human MCF7 cells after 72 hrs by CCK8 assay
|
[PMID: 30071408] |
| MCF7 | IC50 |
5.27 μM
Compound: ZSTK474
|
Antiproliferative activity against human MCF7 cells after 72 hrs by CCK-8 assay
Antiproliferative activity against human MCF7 cells after 72 hrs by CCK-8 assay
|
[PMID: 30245395] |
| MDA-MB-468 | EC50 |
3.2 μM
Compound: ZSTK474
|
Cytotoxicity against PTEN-deficient human MDA-MB-468 cells assessed as inhibition of cell growth after 48 hrs by Cell Titer 96 assay
Cytotoxicity against PTEN-deficient human MDA-MB-468 cells assessed as inhibition of cell growth after 48 hrs by Cell Titer 96 assay
|
[PMID: 23795239] |
| Sf21 | IC50 |
0.003 μM
Compound: 4a, ZSTK474
|
Inhibition of PI3Kdelta (unknown origin) expressed in SF21 cells using phosphatidylinositol as substrate after 60 mins by Kinase-Glo assay
Inhibition of PI3Kdelta (unknown origin) expressed in SF21 cells using phosphatidylinositol as substrate after 60 mins by Kinase-Glo assay
|
[PMID: 23265896] |
| Sf21 | IC50 |
0.006 μM
Compound: 4a, ZSTK474
|
Inhibition of PI3Kalpha (unknown origin) expressed in SF21 cells using phosphatidylinositol as substrate after 60 mins by Kinase-Glo assay
Inhibition of PI3Kalpha (unknown origin) expressed in SF21 cells using phosphatidylinositol as substrate after 60 mins by Kinase-Glo assay
|
[PMID: 23265896] |
| Sf21 | IC50 |
0.006 μM
Compound: 4a, ZSTK474
|
Inhibition of PI3Kbeta (unknown origin) expressed in SF21 cells using phosphatidylinositol as substrate after 60 mins by Kinase-Glo assay
Inhibition of PI3Kbeta (unknown origin) expressed in SF21 cells using phosphatidylinositol as substrate after 60 mins by Kinase-Glo assay
|
[PMID: 23265896] |
| Sf21 | IC50 |
0.038 μM
Compound: 4a, ZSTK474
|
Inhibition of PI3Kgamma (unknown origin) expressed in SF21 cells using phosphatidylinositol as substrate after 60 mins by Kinase-Glo assay
Inhibition of PI3Kgamma (unknown origin) expressed in SF21 cells using phosphatidylinositol as substrate after 60 mins by Kinase-Glo assay
|
[PMID: 23265896] |
| Sf21 | IC50 |
6 nM
Compound: ZSTK-47
|
Inhibition of PI3Kbeta (unknown origin) expressed in Escherichia coli-infected fall armyworm sf21 cells co-expressing p85 by kinase-glo luminescence assay
Inhibition of PI3Kbeta (unknown origin) expressed in Escherichia coli-infected fall armyworm sf21 cells co-expressing p85 by kinase-glo luminescence assay
|
[PMID: 27387421] |
| U-87MG ATCC | IC50 |
0.13 μM
Compound: IV; ZSTK-474
|
Antiproliferative activity against human U-87 MG cells assessed as inhibition of cell proliferation incubated for 96 hrs by MTT assay
Antiproliferative activity against human U-87 MG cells assessed as inhibition of cell proliferation incubated for 96 hrs by MTT assay
|
[PMID: 37736169] |
| U-87MG ATCC | IC50 |
111 nM
Compound: 1, ZSTK474
|
Inhibition of PIK3CA-mediated cell signaling in PTEN-deficient human U87MG cells assessed as inhibition of insulin-induced pAkt/PKB phosphorylation at Ser473 treated for 15 mins before insulin challenge measured after 5 mins by immunoblotting
Inhibition of PIK3CA-mediated cell signaling in PTEN-deficient human U87MG cells assessed as inhibition of insulin-induced pAkt/PKB phosphorylation at Ser473 treated for 15 mins before insulin challenge measured after 5 mins by immunoblotting
|
[PMID: 21882832] |
| U-87MG ATCC | IC50 |
32 nM
Compound: 1, ZSTK474
|
Inhibition of PIK3CA-mediated cell signaling in PTEN-deficient human U87MG cells assessed as inhibition of insulin-induced pAkt/PKB phosphorylation at Thr308 treated for 15 mins before insulin challenge measured after 5 mins by immunoblotting
Inhibition of PIK3CA-mediated cell signaling in PTEN-deficient human U87MG cells assessed as inhibition of insulin-induced pAkt/PKB phosphorylation at Thr308 treated for 15 mins before insulin challenge measured after 5 mins by immunoblotting
|
[PMID: 21882832] |
Lineweaver-Burk plot analysis revealed that ZSTK474 inhibits all four PI3K isoforms in an ATP-competitive manner. The Ki values determined for the four PI3K isoforms showed that ZSTK474 inhibited the PI3Kδ isoform most effectively with a Ki of 1.8 nM, whereas the other isoforms are inhibited with 4-10-fold higher Ki values. Therefore, ZSTK474 should be regarded as a pan-PI3K inhibitor. We also determined the IC50 values for inhibiting the four PI3K isoforms with ZSTK474 and LY294002. The IC50 values of ZSTK474 (16, 44, 4.6 and 49 nM for PI3Kα, PI3Kβ, PI3Kδ and PI3Kγ, respectively) are shown to be consistent with the Ki values (6.7, 10.4, 1.8 and 11.7 nM for PI3Kα, PI3Kβ, PI3Kδ and PI3Kγ, respectively), which further supported the idea that ZSTK474 inhibits PI3Kδ most potently. Even at a concentration of 100 μM, ZSTK474 inhibits mTOR activity rather weakly[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| NCT Number | Sponsor | Condition | Start Date |
Phase
|
|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 475110-96-4
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Appearance Solid
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분자량 417.41
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화학식 C19H21F2N7O2
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Color White to off-white
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SMILES
FC(C1=NC2=C(N1C3=NC(N4CCOCC4)=NC(N5CCOCC5)=N3)C=CC=C2)F
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Publications (18)
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Journal Impact Factor
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Most Recent
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Sci Transl Med
PP2A inhibition is a druggable MEK inhibitor resistance mechanism in KRAS-mutant lung cancer cells. [Abstract]2018 Jul 18;10(450):eaaq1093. PMID: 30021885 -
J Exp Clin Cancer Res
Prolonged inhibition of class I PI3K promotes liver cancer stem cell expansion by augmenting SGK3/GSK-3β/β-catenin signalling. [Abstract]2018 Jun 25;37(1):122. PMID: 29940988
ZSTK474 purchased from MedChemExpress. Usage Cited in: J Exp Clin Cancer Res. 2018 Jun 25;37(1):122. [Abstract]
MHCC97H cells are treated with either LY294002 (2.5, 5,10, 20, 40 μM) or ZSTK474 (0.5, 1, 2.5, 5, 10 μM) for 24 h. DMSO is used as the control. Cell lysates are subjected to western blot analysis with the indicated antibodies.
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Cell Death Dis
2026 Jun 23. PMID: 42336842 -
Clin Cancer Res
Upregulation of IGF1R by mutant RAS in leukemia and potentiation of RAS signaling inhibitors by small-molecule inhibition of IGF1R. [Abstract]2014 Nov 1;20(21):5483-95. PMID: 25186968 -
Neurotherapeutics
Salidroside ameliorates experimental autoimmune neuritis by dually modulating neuroinflammation and immune homeostasis via PI3K/AKT signaling. [Abstract]2025 Nov 7:e00769. PMID: 41206312 -
Mol Metab
The lysosomal LAMTOR / Ragulator complex is essential for nutrient homeostasis in brown adipose tissue. [Abstract]2023 May:71:101705. PMID: 36907508 -
J Endocrinol
2020 Feb;244(2):285-296. PMID: 31693486 -
Molecules
In Vitro and in Vivo Activity of mTOR Kinase and PI3K Inhibitors Against Leishmania donovani and Trypanosoma brucei. [Abstract]2020 Apr 23;25(8):1980. PMID: 32340370 -
BMC Cancer
2024 Jul 26;24(1):902. PMID: 39061024 -
J Biol Chem
Kinome-wide selectivity profiling of ATP-competitive mammalian target of rapamycin (mTOR) inhibitors and characterization of their binding kinetics. [Abstract]2012 Mar 23;287(13):9742-9752. PMID: 22223645 -
Gene
Birch pollen-induced signatures in dendritic cells are maintained upon additional cytomegalovirus exposure. [Abstract]2024 Nov 15:927:148649. PMID: 38852697 -
Exp Ther Med
mTORC1 is a key regulator that mediates OGD- and TGFβ1-induced myofibroblast transformation and chondroitin-4-sulfate expression in cardiac fibroblasts. [Abstract]2022 Jun;23(6):413. PMID: 35601064 -
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Bioengineered
The phosphoinositide 3-kinase inhibitor ZSTK474 increases the susceptibility of osteosarcoma cells to oncolytic vesicular stomatitis virus VSVΔ51 via aggravating endoplasmic reticulum stress. [Abstract]2021 Dec;12(2):11847-11857. PMID: 34720036 -
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용액&용해도
DMSO : 33.33 mg/mL (79.85 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
The following protocol is derived from the literature and is for reference only. It is recommended to first try a small sample.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Working solution concentration: 0.22 mg/mL
Protocol
The linear phase of each kinetic reaction is defined at the respective enzyme amount (0.05, 0.1, 0.12 and 1 µg/mL for PI3Kα, PI3β, PI3δ and PI3γ, respectively) and reaction time (20 min). PI3K activity is assayed at various concentrations of ATP (5, 10, 25, 50, 100 µM) in the presence of increasing concentrations of ZSTK474. A Lineweaver-Burk plot is developed by plotting 1/v (the inverse of v, where v is obtained by subtracting the HTRF signal of the kinase test sample from the HTRF signal of the minus-enzyme control) versus 1/[ATP] (the inverse of the ATP concentration). For the minus-enzyme control, PIP2 is incubated with ATP in the absence of kinase. To determine the Ki value (inhibition constant) of ZSTK474 for each PI3K isoform, the slope of the respective Lineweaver-Burk plot is replotted against the ZSTK474 concentration. The Ki values are calculated by analysis using GraphPad Prism 4[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Mice[2]
Mice are randomly assigned to receive different doses of ZSTK474 (50, 100, 200, and 300 mg/kg) to determine the optimum dose; in our experiment, the optimum dose is 200 mg/kg. Then mice are randomly assigned to one of three groups: a sham-operated group (phosphate-buffered saline, PBS); a control group (MCAO+PBS); a ZSTK474-treated group (MCAO+ZSTK474). In the ZSTK474-treated group, the mice are given the optimum dose of 200 mg/kg ZSTK474. In the sham-operated group and control group, mice are given an equivalent volume of PBS. All mice receive that same dose daily via oral gavage beginning at 6 h after the onset of focal ischemia and continuing for two more days, i.e., for a total of 3 days.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
순도&문서
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Data Sheet (288 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
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Handling Instructions (2659 KB)
References
[1]. Kong D, et al. ZSTK474 is an ATP-competitive inhibitor of class I phosphatidylinositol 3 kinase isoforms. Cancer Sci, 2007, 98(10), 1638-1642. [Content Brief]
[2]. Liu F, et al. Prolonged inhibition of class I PI3K promotes liver cancer stem cell expansion by augmenting SGK3/GSK-3β/β-catenin signalling. J Exp Clin Cancer Res. 2018 Jun 25;37(1):122. [Content Brief]
[3]. Wang P, et al. Class I PI3K inhibitor ZSTK474 mediates a shift in microglial/macrophage phenotype and inhibits inflammatory response in mice with cerebral ischemia/reperfusion injury. J Neuroinflammation. 2016 Aug 22;13(1):192. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.3957 mL | 11.9786 mL | 23.9573 mL | 59.8932 mL |
| 5 mM | 0.4791 mL | 2.3957 mL | 4.7915 mL | 11.9786 mL | |
| 10 mM | 0.2396 mL | 1.1979 mL | 2.3957 mL | 5.9893 mL | |
| 15 mM | 0.1597 mL | 0.7986 mL | 1.5972 mL | 3.9929 mL | |
| 20 mM | 0.1198 mL | 0.5989 mL | 1.1979 mL | 2.9947 mL | |
| 25 mM | 0.0958 mL | 0.4791 mL | 0.9583 mL | 2.3957 mL | |
| 30 mM | 0.0799 mL | 0.3993 mL | 0.7986 mL | 1.9964 mL | |
| 40 mM | 0.0599 mL | 0.2995 mL | 0.5989 mL | 1.4973 mL | |
| 50 mM | 0.0479 mL | 0.2396 mL | 0.4791 mL | 1.1979 mL | |
| 60 mM | 0.0399 mL | 0.1996 mL | 0.3993 mL | 0.9982 mL |