Dot1L-IN-4 is a potent disruptor of telomeric silencing 1-like protein ( DOT1L ) inhibitor with an IC 50 SPA DOT1L of 0.11 nM
In Vitro
Dot1L-IN-4 (Compound 10) is tested in cellular assays to assess the ability to inhibit the dimethylation of H3K79 in HeLa cells (ED 50 H3K79me2 Elisa =1.7 nM) and HOXA9 gene expression in Molm-13 cells (ED 50 HOXA9 RGA =33 nM). Dot1L-IN-4 also inhibits mixed lineage leukemia (MLL) with an IC 50 of 99 µM. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
Dot1L-IN-4 (Compound 10; 300 mg/kg; p.o.; qd) is not tolerated at such a high dose by tumor xenograft bearing mice, and at a 6-fold reduced dose, the tumor growth as well as the HOXA9 reporter gene mRNA are reduced only by less than half as compared to control animals . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Male mice (C57BL/6) bearing subcutaneous MV4-11 tumor xenografts Dosage: 300 mg/kg (Pharmacokinetic Analysis) Administration: P.o. Result: Was not tolerated at such a high dose by tumor xenograft bearing mice, and at a 6-fold reduced dose, the tumor growth as well as the HOXA9 reporter gene mRNA were reduced only by less than half as compared to control animals.
IC50& Target:DOT1L 0.11 nM (IC 50 )
Associated Targets
DOT1LTchem Histone-lysine N-methyltransferase, H3 lysine-79 specific 1 Activities
