475110-96-4
475110-96-4 structure
- Name: ZSTK474
- Chemical Name: 4-[4-[2-(difluoromethyl)benzimidazol-1-yl]-6-morpholin-4-yl-1,3,5-triazin-2-yl]morpholine
- CAS Number: 475110-96-4
- Molecular Formula: C19H21F2N7O2
- Molecular Weight: 417.413
- Catalog: Biochemical Inhibitor PI3K/Akt/mTOR inhibitor (PI3K/Akt/mTOR) PI3K inhibitor
- Create Date: 2019-01-01 17:17:42
- Modify Date: 2024-01-02 19:38:39
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ZSTK474 is an ATP-competitive pan-class I PI3K inhibitor with IC50s of16 nM, 44 nM, 4.6 nM and 49 nM for PΙ3Κα, PI3Kβ, PI3Kδ and PI3Kγ, respectively.
| Name | 4-[4-[2-(difluoromethyl)benzimidazol-1-yl]-6-morpholin-4-yl-1,3,5-triazin-2-yl]morpholine |
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| Synonyms |
2wxl
1H-Benzimidazole, 2-(difluoromethyl)-1-(4,6-di-4-morpholinyl-1,3,5-triazin-2-yl)- ZSTK474 2-(Difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole ZSTK-474,ZST K474 ZSTK-474 TCMDC-137004 S1072_Selleck 2-(Difluoromethyl)-1-[4,6-di(morpholin-4-yl)-1,3,5-triazin-2-yl]-1H-benzimidazole 4,4'-(6-(2-(difluoromethyl)-1H-benzo[d]imidazol-1-yl)-1,3,5-triazine-2,4-diyl)dimorpholine |
| Description | ZSTK474 is an ATP-competitive pan-class I PI3K inhibitor with IC50s of16 nM, 44 nM, 4.6 nM and 49 nM for PΙ3Κα, PI3Kβ, PI3Kδ and PI3Kγ, respectively. |
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| Related Catalog | |
| Target |
PI3Kα:16 nM (IC50) PI3Kβ:44 nM (IC50) PI3Kδ:4.6 nM (IC50) PI3Kγ:49 nM (IC50) Autophagy |
| In Vitro | 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]. |
| 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]. |
| Kinase Assay | 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]. |
| Animal Admin | 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. |
| References |
| Density | 1.6±0.1 g/cm3 |
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| Boiling Point | 640.3±65.0 °C at 760 mmHg |
| Molecular Formula | C19H21F2N7O2 |
| Molecular Weight | 417.413 |
| Flash Point | 341.0±34.3 °C |
| Exact Mass | 417.172485 |
| PSA | 81.43000 |
| LogP | -0.21 |
| Vapour Pressure | 0.0±1.9 mmHg at 25°C |
| Index of Refraction | 1.711 |
| Storage condition | -20°C |
| HS Code | 2934999090 |
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| HS Code | 2934999090 |
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| Summary | 2934999090. other heterocyclic compounds. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0% |