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。

RUNX1/ETO tetramerization-IN-1 is a small-molecule inhibitor of RUNX1/ETO tetramerization, exhibits anti-leukemic effect. RUNX1/ETO tetramerization-IN-1 specifically targets to NHR2 of RUNX1/ETO ( EC 50 =0.25 μM), restores gene expression down-regulated by RUNX1/ETO. RUNX1/ETO tetramerization-IN-1 inhibits the proliferation of RUNX1/ETO -depending SKNO-1 cells, and reduces the RUNX1/ETO -related tumor growth in a mouse model [1] [2] [3].

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 [1]. 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) [2]. RUNX1/ETO tetramerization-IN-1 (100 μM; 7 d) induces growth-arrest and differentiation of RUNX1/ETOtr-expressing CD34 + progenitor cells [2]. 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 [3]. RUNX1/ETO tetramerization-IN-1 (1 μM and 10 μM) shows a potential to inhibit CYP2B6, 2C9, 2C19, and 3A4 [3]. 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 [4]. Cell Viability Assay [1] Cell Line: RUNX1/ETO-dependent human leukemic SKNO-1 and U937 cells Concentration: 1 μM and 10 μM Incubation Time: 3, 5, 7 days Result: Inhibited the SKNO-1 cell growth specifically. Cell Viability Assay [3] Cell Line: Pharmacokinetic properties of RUNX1/ETO tetramerization-IN-1 Concentration: Incubation Time: Result: Kinetic solubility (99% PBS, 1% DMSO) 177 μM Plasma protein binding (mouse plasma, 60 min) 98.4% Plasma stability (mouse plasma, 0–240 min) No degradation Hepatocyte stability (mouse hepatocytes) 2.5 μL/min/million cells Chemical stability in PBS (0–4 h) No degradation

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 [2]. Animal Model: NSG immunodeficient mice (NOD.Cg-Prkdc scid Il2rg tm1WjI /SzJ) injected with Kasumi-1 cells [2] Dosage: 200-250 μg/Kg Administration: Intraperitoneal injection; 5 times per week, for 130 days Result: Reduced the dissemination of leukemic cells, remained 75% mice alive at day 130 post-treatment.

88755-39-9

C18H14O7

342.3

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years