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。
| 生物活性 | RUNX1/ETO tetramerization-IN-1 is a small-molecule inhibitor ofRUNX1/ETO tetramerization, exhibits anti-leukemic effect. RUNX1/ETO tetramerization-IN-1 specifically targets toNHR2ofRUNX1/ETO(EC50=0.25 μM), restores gene expression down-regulated byRUNX1/ETO. RUNX1/ETO tetramerization-IN-1 inhibits the proliferation ofRUNX1/ETO-depending SKNO-1 cells, and reduces theRUNX1/ETO-related tumor growth in a mouse model[1][2][3]. |
| IC50& Target | IC50: 630 μM (RUNX1-NHR2 tetramerization)[1] |
体外研究
(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[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 |
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体内研究
(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[2].
| Animal Model: | NSG immunodeficient mice (NOD.Cg-PrkdcscidIl2rgtm1WjI/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. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
