475110-96-4

Basic information

• Product Name: ZSTK474
• Synonyms: 2-(2-Difluoromethylbenzimidazol-1-yl)-4,6-dimorpholino-1,3,5-triazine;ZSTK 474;4,4'-(6-(2-(difluoromethyl)-1H-benzo[d]imidazol-1-yl)-1,3,5-triazine-2,4-diyl)dimorpholine;2-(DifluoroMethyl)-1-[4,6-di(4-Morpholinyl)-1,3,5-triazin-2-yl]-1H-benziMidazole;1H-BenziMidazole, 2-(difluoroMethyl)-1-(4,6-di-4-Morpholinyl-1,3,5-triazin-2-yl)-;ZSTK474/ZSTK-474;2-(difluoromethyl)-1-(4,6-dimorpholino-1,3,5-triazin-2-yl)-1H-benzo[d]imidazole;2-(2-Difluoromethylbenzimidazol-1-yl)-4,6-dimorpholino-1,3,5-triazine ZSTK-474
• CAS NO: 475110-96-4
• Molecular Formula: C19H21F2N7O2
• Molecular Weight: 417.418
• Product Categories: Inhibitors;Akt;mTOR;PI3K
• Mol File: 475110-96-4.mol
• Article Data: 8

Chemical Properties

• Boiling Point: 640.267 °C at 760 mmHg
• Flash Point: 341.021 °C
• Appearance: /
• Density: 1.57
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.711
• Storage Temp.: -20°C
• Solubility: Soluble in DMSO (up to 20 mg/ml) or in Ethanol (up to 2.5 mg/ml with warming).
• PKA: 5.21±0.10(Predicted)
• 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.
• CAS DataBase Reference: ZSTK474(CAS DataBase Reference)
• NIST Chemistry Reference: ZSTK474(475110-96-4)
• EPA Substance Registry System: ZSTK474(475110-96-4)

Safety Data

• Hazardous Substances Data: 475110-96-4(Hazardous Substances Data)

Usage

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

Different sources of media describe the Uses of 475110-96-4 differently. You can refer to the following data:
1. 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.
2. 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.

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

InChI:InChI=1/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

Upstream product

• 110-91-8 morpholine 
• 475111-38-7 4-(4-chloro-6-(2-(difluoromethyl)-1H-benzo[d]imidazole -1-yl)-1,3,5-triazin-2-yl)morpholine 
• 7597-22-0 2-chloro-4,6-di-morpholin-4-yl-[1,3,5]triazine 
• 705-09-9 2-(difluoromethyl)-1H-benzo[d]imidazole 
• 95-54-5 1,2-diamino-benzene 

Relevant articles and documents

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PIPERAZINOTRIAZINES AS PI3K INHIBITORS FOR USE IN THE TREATMENT ANTIPROLIFERATIVE DISORDERS

The invention relates to compounds of formula (I) R1 is methyl, n-hexyl, aminoethyl, methylaminoethyl, ethylaminoethyl, dimethylaminoethyl, acryloylaminoethyl, methacryloylaminoethyl, methoxyethyl, ethoxyethyl, d-C4-alkyl-sulfonyl, acryloyl, or methacryloyl; or R1 is aminoethyl, acryloyl or acryloylaminoethyl carrying a linker and a tag, and R2 and R3, independently of each other, are hydrogen or CrC4-alkyl, or R2 and R3 together form a methylene or an ethylene bridge; and tautomers, solvates and pharmaceutically acceptable salts thereof. These compounds are effective in preventing or treating a disease or disorder modulated by PI3 kinases and/or mTOR, in particular treating a hyperproliferative disorder.

PIPERAZINOTRIAZINES AS PI3K INHIBITORS FOR USE IN THE TREATMENT ANTIPROLIFERATIVE DISORDERS

The invention relates to compounds of formula (I) R1 is methyl, n-hexyl, aminoethyl, methylaminoethyl, ethylaminoethyl, dimethylaminoethyl, acryloylaminoethyl, methacryloylaminoethyl, methoxyethyl, ethoxyethyl, d-C4-alkyl- sulfonyl, acryloyl, or methacryloyl; or R1 is aminoethyl, acryloyl or acryloylaminoethyl carrying a linker and a tag, and R2 and R3, independently of each other, are hydrogen or CrC4-alkyl, or R2 and R3 together form a methylene or an ethylene bridge; and tautomers, solvates and pharmaceutically acceptable salts thereof. These compounds are effective in preventing or treating a disease or disorder modulated by PI3 kinases and/or mTOR, in particular treating a hyperproliferative disorder.