ZSTK474 Property

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.

Safety

HS Code 

29349990

Hazard and Precautionary Statements (GHS)

ZSTK474 Chemical Properties,Usage,Production

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ChEBI: A triamino-1,3,5-triazine that is 1,3,5-triazine in which two of the hydrogens have been replaced by morpholin-4-yl groups while the third hydrogen has been replaced by a 2-(difluoromethyl)benzimidazol-1-yl group.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

target

PI3Kδ

References

1) Kong and Yamori et al. (2007), ZSTK474 is an ATP-competitive inhibitor of class I phosphatidylinositol 3 kinase isoforms; Cancer Sci., 98 1638 2) Yaguchi et al. (2006), Antitumor activity of ZST474, a new phosphatidylinositol 3-kinase inhibitor; J. Natl. Cancer Inst., 98 545 3) Xue et al. (2014), ZSTK474, a novel PI3K inhibitor, modulates human CD14+ monocyte-derived dendritic cell functions and suppresses experimental autoimmune encephalomyelitis; J. Mol. Med. (Berl.), 92 1057 4) Haruta et al. (2012), Inhibitory effects of ZST474, a phosphatidylinositol 3-kinase inhibitor, on adjuvant-induced arthritis in rats; Inflamm. Res., 61 551