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RUNX1/ETO tetramerization-IN-1

CAS No. : 88755-39-9

MCE 站：RUNX1/ETO tetramerization-IN-1

产品活性：RUNX1/ETO tetramerization-IN-1 是 RUNX1/ETO 四聚化的小分子抑制剂，具有抗白血病作用。RUNX1/ETO tetramerization-IN-1 可特异靶向 RUNX1/ETO 的 NHR2 (EC₅₀=0.25 μM)，恢复 RUNX1/ETO 下调的基因表达。RUNX1/ETO tetramerization-IN-1抑制RUNX1/ETO依赖性 SKNO-1 细胞增殖，在小鼠模型中抑制 RUNX1/ETO 相关肿瘤生长。

研究领域：Others

作用靶点：Others

In Vitro: RUNX1/ETO is composed by the DNA-binding Runt-domain5, the product of the RUNX1 gene, ａnd by four nervy homology regions (NHR1-4), the product of the ETO gene. The NHR2 domain is responsible for the tetramerization of RUNX1/ETO.
RUNX1/ETO tetramerization-IN-1 (compound 7.44) (1 μM ａnd 10 μM; 3, 5, 7 d) selectively reduces the viability of RUNX1/ETO-dependent human leukemic SKNO-1 cells instead of U937 cells.
RUNX1/ETO tetramerization-IN-1 (compound 7.44) (25 μM ａnd 50 μM; 5 d) inhibits the growth of ａnd induces myeloid differentiation in RUNX1/ETO-expressing cells (SKNO-1, Kasumi-1, ａnd K562).
RUNX1/ETO tetramerization-IN-1 (100 μM; 7 d) induces growth-arrest ａnd differentiation of RUNX1/ETOtr-expressing CD34⁺ progenitor cells.
RUNX1/ETO tetramerization-IN-1 (compound 7.44) has favorable physicochemical ａnd ADME properties with high aqueous solubility, high stability in buffer ａnd plasma, ａnd a low hepatic intrinsic clearance in vitro, with the aqueous solubility of 60 μg/mL.
RUNX1/ETO tetramerization-IN-1 (1 μM ａnd 10 μM) shows a potential to inhibit CYP2B6, 2C9, 2C19, ａnd 3A4.
RUNX1/ETO tetramerization-IN-1 (compound 8) (50 μM; 16 h) inhibits c-Jun N-terminal kinase (JNK) ａnd affect the JNK-pathway in cells.

In Vivo: RUNX1/ETO tetramerization-IN-1 (compound 7.44) (200-250 μg/kg; i.p.; 5 times per week; 130 d) delays tumor growth of RUNX1/ETO cells in mice.

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