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Chemical Structure| 475110-96-4 Chemical Structure| 475110-96-4

Structure of ZSTK474
CAS No.: 475110-96-4

Chemical Structure| 475110-96-4

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ZSTK474 is an ATP-competitive pan-class I PI3K inhibitor with IC50 values of 16 nM for PI3Kα, 44 nM for PI3Kβ, 4.6 nM for PI3Kδ, and 49 nM for PI3Kγ.

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Product Details of ZSTK474

CAS No. :475110-96-4
Formula : C19H21F2N7O2
M.W : 417.41
SMILES Code : FC(C1=NC2=CC=CC=C2N1C3=NC(N4CCOCC4)=NC(N5CCOCC5)=N3)F
InChI Key :HGVNLRPZOWWDKD-UHFFFAOYSA-N
Pubchem ID :11647372

Safety of ZSTK474

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of ZSTK474

PI3K-AKT

Isoform Comparison

Biological Activity

Target
  • p110γ

    PI3Kγ, IC50:49 nM

  • p110β

    PI3Kβ, IC50:44 nM

  • p110α

    PI3Kα, IC50:16 nM

  • PI3K

    PI3K, IC50:37 nM

  • p110δ

    PI3Kδ, IC50:4.6 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
MCF7 cells 10 µM 1 h Inhibition of PI3K signaling pathway to observe its effect on ERK activation Nat Commun. 2018 Nov 7;9(1):4673.
A431 cells 1 µM 6 h To evaluate the effect of ZSTK474 on apoptosis in A431 cells, results showed that CD151 knockdown increased ZSTK474-induced apoptosis. Cell Mol Life Sci. 2019 Apr;76(8):1595-1604.
LM-EV 30 μM 7 days To study the effect of ZSTK474 on the viability of LM-EV cells in suspension culture, results showed that ZSTK474 significantly reduced the viability of LM-EV cells Breast Cancer Res. 2016 Aug 5;18(1):81.
BT549-EV 30 μM 7 days To study the effect of ZSTK474 on the viability of BT549-EV cells in suspension culture, results showed that ZSTK474 significantly reduced the viability of BT549-EV cells Breast Cancer Res. 2016 Aug 5;18(1):81.
REH cells 4 µM 48 h To evaluate the synergistic anticancer effect of ZSTK474 combined with AZD0364 on REH cells, the results showed that the combination treatment significantly reduced cell viability, increased ROS production, and induced apoptosis. Antioxidants (Basel). 2020 Jul 17;9(7):633.
MOLT-4 cells 0.5 µM 48 h To evaluate the synergistic anticancer effect of ZSTK474 combined with AZD0364 on MOLT-4 cells, the results showed that the combination treatment significantly reduced cell viability, increased ROS production, and induced apoptosis. Antioxidants (Basel). 2020 Jul 17;9(7):633.
MOLM-14 cells 0.5 µM 48 h To evaluate the synergistic anticancer effect of ZSTK474 combined with AZD0364 on MOLM-14 cells, the results showed that the combination treatment significantly reduced cell viability, increased ROS production, and induced apoptosis. Antioxidants (Basel). 2020 Jul 17;9(7):633.
K562 cells 8 µM 48 h To evaluate the anticancer effect of ZSTK474 combined with AZD0364 on K562 cells, the results showed that the combination treatment had an antagonistic effect on K562 cells. Antioxidants (Basel). 2020 Jul 17;9(7):633.
RAW264.7 cells 0.1 μM 30 min ZSTK474 suppressed the phosphorylation of Akt induced by sRANKL, indicating its inhibitory effect on the PI3-K/Akt signaling pathway. Arthritis Res Ther. 2010;12(3):R92.
mature osteoclasts 0.1 μM 72 h ZSTK474 completely inhibited the bone-resorbing activity of mature osteoclasts. Arthritis Res Ther. 2010;12(3):R92.
Huh7 5 μM 24 h The combination of ZSTK474 and PIK3C3 inhibitor significantly suppressed the expression of stemness genes and effectively reduced the proportion of CD133+ cells. Cell Death Dis. 2020 Jun 8;11(6):427.
MHCC97H 5 μM 24 h The combination of ZSTK474 and PIK3C3 inhibitor significantly suppressed the expression of stemness genes and effectively reduced the proportion of CD133+ cells. Cell Death Dis. 2020 Jun 8;11(6):427.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
C57BL/6 mice Cerebral ischemia/reperfusion injury model Oral 200 mg/kg Once daily for 3 days ZSTK474 alleviated neurological deficits, reduced infarct volume, and shifted the phenotype of microglia/macrophages, inhibiting the inflammatory response in the cerebral ischemia/reperfusion injury model. J Neuroinflammation. 2016 Aug 22;13(1):192
Mice Cerebral ischemia/reperfusion injury model Oral gavage 200 mg/kg Once daily for 3 days ZSTK474 alleviated neurological deficits, reduced infarct volume, and improved neurological function in the cerebral ischemia/reperfusion injury model. J Neuroinflammation. 2016 Aug 22;13(1):192
Mice Collagen-induced arthritis (CIA) model Oral 25, 50, 100 mg/kg Once daily until the end of the experiment ZSTK474 significantly alleviated arthritis symptoms in the CIA model, reduced inflammatory cell infiltration and cartilage/bone destruction, and significantly decreased osteoclast formation. Arthritis Res Ther. 2010;12(3):R92.
Nude mice Subcutaneous xenograft model Oral 200 mg/kg Once daily for 10 days The combination of ZSTK474 and PIK3C3 inhibitor significantly suppressed tumor growth and reduced the proportion of CD133+ cells in tumors. Cell Death Dis. 2020 Jun 8;11(6):427.

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT01682473 Neoplasms PHASE1 COMPLETED 2015-04-20 National Cancer Center Hospita... More >>l East, Kashiwa-city, Chiba, Japan|The Cancer Institute Hospital of JFCR, Koto-ku, Tokyo, Japan Less <<
NCT01280487 Neoplasms PHASE1 COMPLETED 2025-01-14 Dana Farber Cancer Institute, ... More >>Boston, Massachusetts, United States|Washington University, St Louis, Missouri, United States|Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.40mL

0.48mL

0.24mL

11.98mL

2.40mL

1.20mL

23.96mL

4.79mL

2.40mL

References

 

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