TN1

Research use only, not for human use.

TN1 is a potent inducer of fetal hemoglobin (HbF).

TN1 is a potent fetal hemoglobin (HbF) inducer.

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 EC50 value for TN1-mediated HbF induction is approximately three orders of magnitude lower than that of HU (HU: EC50=50-100 μM; TN1: EC50=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.

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Others

Other Targets

Others

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289479-94-3

509.6

C29H31N7O2

>98% (HPLC)

In Vitro:?DMSO : 100 mg/mL (196.23 mM; Ultrasonic )

CCn1cnc2c(Nc3cccc(NC(=O)C#Cc4ccc(C)cc4)c3)nc(N[C@H]3CC[C@H](O)CC3)nc12

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(-20℃)

With Ice Pack

≥ 2 years