Eleven-Nineteen-Leukemia Protein IN-3, an orally active ENL YEATS domain inhibitor, exhibits potent activity with an IC50 of 15.4 nM. It downregulates MYC expression via ENL in cells and enhances ENL protein's thermal stability in vitro [1].

Eleven-Nineteen-Leukemia Protein IN-3 (Compound 28) exhibits significant inhibitory effects on the MV4-11 and MOLM-13 cell lines with IC50 values of 4.8 µM and 8.3 µM, respectively [1]. When applied at a concentration of 5 µM for 6 hours, it notably increases the thermal stability of the endogenous ENL protein, while it does not significantly affect the thermal stability of the GAS41 protein. Furthermore, Eleven-Nineteen-Leukemia Protein IN-3 effectively inhibits the growth of MOLM-13 cells [1]. At a concentration of 5 µM over 72 hours, it suppresses the expression of the crucial oncogene MYC by approximately 50%. In combination with JQ-1, Eleven-Nineteen-Leukemia Protein IN-3 further downregulates the expression of MYC in ENL target genes [1].

Eleven-Nineteen-Leukemia Protein IN-3 (Compound 28) demonstrated oral bioavailability characteristics at a dose of 30 mg/kg when administered orally as a single dose [1]. When given intravenously at a dose of 5 mg/kg as a single injection, the compound exhibited higher systemic exposure in the body [1]. Pharmacokinetic (PK) studies in male BALB/c mice revealed the following parameters: for oral administration, the half-life (t 1/2) was 5.2 hours, time to peak concentration (T max) was 0.5 hours, maximum concentration (C max) was 71.8 ng/mL, area under the curve to the last measurable concentration (AUC 0-t) was 257 h•ng/mL, the extrapolated AUC (AUC 0-∞) was 272 h•ng/mL, and mean residence time (MRT 0-∞) was 5.5 hours. For intravenous administration, the t 1/2 was 4.0 hours, AUC 0-t was 8290 h•ng/mL, AUC 0-∞ was 8690 h•ng/mL, volume of distribution at steady state (V ss) was 0.8 L/kg, clearance (CL) was 9.6 mL/min/kg, MRT 0-∞ was 1.3 hours, and bioavailability (F %) was 0.5%.