中文名 | TN1 |
英文名 | TN1 |
别名 | 化合物 T19583 |
英文别名 | TN1 2-Propynamide, N-[3-[[9-ethyl-2-[(trans-4-hydroxycyclohexyl)amino]-9H-purin-6-yl]amino]phenyl]-3-(4-methylphenyl)- |
CAS | 289479-94-3 |
化学式 | C29H31N7O2 |
分子量 | 509.6 |
密度 | 1.31±0.1 g/cm3(Predicted) |
溶解度 | 10毫米DMSO |
酸度系数 | 10.49±0.70(Predicted) |
存储条件 | -20℃ |
体外研究 | A high-throughput screen of a large chemical library identifies a 2,6-diamino-substituted purine, TN1, which induces fetal hemoglobin (HbF) more potently than hydroxyurea in KU812 and K562 leukemia cell lines.TN1 increases HbF protein in both leukemic KU812 and K562 cells in a dose-dependent manner. At 100 nM concentration, Western blot analysis indicated that TN1 increased γ-globin expression (2.9- and 3.7-fold increase in KU812 cell and K562 cell, respectively) to higher levels than 50-100 μM HU (1.8- and 1.9-fold increase in KU812 cell and K562 cell, respectively), the first drug approved for the treatment of SCD. The EC 50 value for TN1-mediated HbF induction is approximately three orders of magnitude lower than that of HU (HU: EC 50 =50-100 μM; TN1: EC 50 =100 nM). In addition, TN1 is more potent than a number of previously reported small-molecule HbF inducers including sodium butyrate and other histone deacetylase (HDAC) inhibitors. At the concentrations tested, TN1, as well as hemin and HU, increase γ-globin mRNA transcription (greater than fourfold), indicating that TN1 increases γ-globin levels at both the transcriptional and protein level. The time course of TN1-induced γ-globin mRNA and protein synthesis is measured and both increase after approximately 24 h of treatment. TN1 also induces β-globin mRNA in addition to γ-globin mRNA, similar to hydroxyurea. |
1mg | 5mg | 10mg | |
---|---|---|---|
1 mM | 1.962 ml | 9.812 ml | 19.623 ml |
5 mM | 0.392 ml | 1.962 ml | 3.925 ml |
10 mM | 0.196 ml | 0.981 ml | 1.962 ml |
5 mM | 0.039 ml | 0.196 ml | 0.392 ml |
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