Dot1L-IN-4 is a potent disruptor of telomeric silencing 1-like protein (DOT1L) inhibitor with an IC50 SPA DOT1L of 0.11 nM.
IC50&Target
DOT1L
0.11 nM (IC50)
体外研究
Dot1L-IN-4 (Compound 10) is tested in cellular assays to assess the ability to inhibit the dimethylation of H3K79 in HeLa cells (ED50 H3K79me2 Elisa=1.7 nM) and HOXA9 gene expression in Molm-13 cells (ED50 HOXA9 RGA=33 nM). Dot1L-IN-4 also inhibits mixed lineage leukemia (MLL) with an IC50 of 99 µM.
体内研究
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.
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.
分子式
C28H27ClF2N8O5S
分子量
661.08
CAS号
2565705-02-2
运输条件
Room temperature in continental US; may vary elsewhere.