| Hazard Information | Back Directory | [Uses]
Eleven-Nineteen-Leukemia Protein IN-3 is an orally active inhibitor of ENL YEATS domain with an IC50 value of 15.4 nM. Eleven-Nineteen-Leukemia Protein IN-3 down-regulates MYC expression through ENL in cells and can enhances the thermal stability of ENL protein in vitro[1]. | [in vivo]
Eleven-Nineteen-Leukemia Protein IN-3 (Compound 28) (30 mg/kg; p.o.; single dose) shows oral exposure characteristics[1].
Eleven-Nineteen-Leukemia Protein IN-3 (5 mg/kg; i.v.; single dose) highly exposes in vivo[1].
Pharmacokinetic (PK) study in Male BALB/c mice[1]
| Administration | t1/2 (h) | Tmax (h) | Cmax (ng/mL) | AUC0-t (h?ng/mL) | AUC0-∞ (h?ng/mL) | MRT0-∞ (h) | | p.o. | 5.2 | 0.5 | 71.8 | 257 | 272 | 5.5 | |
| Administration | t1/2 (h) | AUC0-t (h?ng/mL) | AUC0-∞ (h?ng/mL) | Vss (L/kg) | CL (mL/min/kg) | MRT0-∞ (h) | F (%) | | i.v. | 4.0 | 8290 | 8690 | 0.8 | 9.6 | 1.3 | 0.5 |
| Animal Model: | Male BALB/c mice[1]. | | Dosage: | 30 mg/kg. | | Administration: | Oral gavage; single dose. | | Result: | Showed an oral activity. |
| Animal Model: | Male BALB/c mice[1]. | | Dosage: | 5 mg/kg. | | Administration: | Intravenous injection; single dose. | | Result: | Exhibited efficacy. |
| [IC 50]
Eleven-Nineteen-Leukemia YEATS domain: 15.4 nM (IC50) | [References]
[1] Guo S, et al. Design, synthesis of novel benzimidazole derivatives as ENL inhibitors suppressing leukemia cells viability via downregulating the expression of MYC. Eur J Med Chem. 2023 Feb 15;248:115093. DOI:10.1016/j.ejmech.2023.115093 |
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