ChemicalBook Product Catalog Biochemical Engineering Inhibitors PI3K / Akt / mTOR PI3K inhibitor ZSTK474

ZSTK474

Product NameZSTK474
CAS475110-96-4
MFC19H21F2N7O2
MW417.41
EINECS
MOL File475110-96-4.mol

Chemical Properties

Melting point	217-219 °C(Solv: ethanol (64-17-5))
Boiling point	640.3±65.0 °C(Predicted)
Density	1.57
storage temp.	-20°C
solubility	Soluble in DMSO (up to 20 mg/ml) or in Ethanol (up to 2.5 mg/ml with warming).
form	White powder.
pka	5.21±0.10(Predicted)
color	White or off-white
Stability	Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 3 months.
InChI	InChI=1S/C19H21F2N7O2/c20-15(21)16-22-13-3-1-2-4-14(13)28(16)19-24-17(26-5-9-29-10-6-26)23-18(25-19)27-7-11-30-12-8-27/h1-4,15H,5-12H2
InChIKey	HGVNLRPZOWWDKD-UHFFFAOYSA-N
SMILES	C1(C(F)F)N(C2=NC(N3CCOCC3)=NC(N3CCOCC3)=N2)C2=CC=CC=C2N=1

Safety Information

WGK Germany	WGK 3
HS Code	29349990
Storage Class	11 - Combustible Solids

Usage And Synthesis

Description

ZSTK474 (475110-96-4) is a novel Class I phosphatidylinositol 3-kinase (PI3K) inhibitor. ZSTK474 is an ATP-competitive inhibitor of all four Class I PI3K isoforms. However, it inhibits PI3Kδ most potently, with a Ki of 1.8 nM, while inhibiting the α, β and γ isoforms at slightly higher concentrations (6.7 nM, 10.4 nM and 11.7 nM, respectively)1. Displays potent antitumor activity against human cancer xenografts (A549, PC-3 and WiDr) when administered to mice2. ZSTK474 displays potent anti-inflammatory activity via modulation of human CD14+ monocyte-derived dendritic cell functions and suppresses experimental autoimmune encephalomyelitis3. Ameliorates the progression of adjuvant-induced arthritis in a rat model4.

Uses

ZSTK474 is a triazine derivative that acts as an inhibitor of class I phosphatidylinositol 3-kinase (PI3K) isoforms (IC50s = 17, 53, and 6 nM for p110β, -γ, and -δ, respectively). It is selective for PI3K, as it has negligible activity against 139 other kinases when tested at 30 μM. ZSTK474 is orally bioavailable and shows strong antitumor activity against human cancer xenografts in mice. The efficacy of ZSTK474 against certain cancer cells and tumors can be enhanced by combination therapy.

Uses

ZSTK474 is an ATP-competitive inhibitor of class I phosphatidylinositol 3 kinase (PI3K) isoforms. Potent PI3K inhibitor.

Definition

ChEBI: A triamino-1,3,5-triazine that is 1,3,5-triazine in which two of the hydrogens have been replaced by morpholin-4-yl groups while the third hydrogen has been replaced by a 2-(difluoromethyl)benzimidazol-1-yl group. It is an inhibitor of phosphatidylinositol 3-kinase.

in vivo

In mice subjected to MCAO, treatment with ZSTK474 is tested at dosages of 50, 100, 200, and 300 mg/kg. Since the 200 mg/kg dose produces significant improvement and no obvious toxic effects (P<0.01), mice are treated with ZSTK474 at a dose of 200 mg/kg/day daily for three post-MCAO days during the remaining experiments of this study. Neurological function is examined in mice suffered from MCAO followed by 24, 48, and 72 h of reperfusion. In the ZSTK474 group, neurological function scores are significantly better than the control group except the corner test^[2].

target

PI3Kδ

IC 50

PI3Kδ: 4.6 nM (IC₅₀); PI3Kα: 16 nM (IC₅₀); PI3Kβ: 44 nM (IC₅₀); PI3Kγ: 49 nM (IC₅₀); Autophagy

References

[1] DEXIN KONG Takao Y. ZSTK474 is an ATP-competitive inhibitor of class I phosphatidylinositol 3 kinase isoforms[J]. Cancer Science, 2007, 98 10: 1638-1642. DOI:10.1111/j.1349-7006.2007.00580.x
[2] SHIN-ICHI YAGUCHI. Antitumor activity of ZSTK474, a new phosphatidylinositol 3-kinase inhibitor.[J]. JNCI Journal of the National Cancer Institute, 2006, 98 8: 545-556. DOI:10.1093/jnci/djj133
[3] ZHENYI XUE. ZSTK474, a novel PI3K inhibitor, modulates human CD14+ monocyte-derived dendritic cell functions and suppresses experimental autoimmune encephalomyelitis.[J]. Journal of Molecular Medicine-Jmm, 2014, 92 10: 1057-1068. DOI:10.1007/s00109-014-1158-x
[4] KAZUHIKO HARUTA. Inhibitory effects of ZSTK474, a phosphatidylinositol 3-kinase inhibitor, on adjuvant-induced arthritis in rats.[J]. Inflammation Research, 2012: 551-562. DOI:10.1007/s00011-012-0444-8

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