Dot1L-IN-4

Research use only, not for human use.

Dot1L-IN-4 is a potent disruptor of telomeric silencing 1-like protein (DOT1L) inhibitor.

Dot1L-IN-4 is a potent disruptor of telomeric silencing 1-like protein (DOT1L) inhibitor.

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.

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 xenograftsDosage: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.

N1-[(3-Chloro-pyridin-2-yl)-(2,2-difluoro-benzo[1,3]dioxol-4-yl)-methyl]-4-methanesulfonyl-N2-(4-methoxy-6-piperazin-1-yl-[1,3,5]triazin-2-yl)-benzene-1,2-diamine

Chromatin/Epigenetic

Histone Demethylase

DOT1L

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2565705-02-2

661.08

C28H27ClF2N8O5S

>98% (HPLC)

DMSO:245 mg/mL (370.61 mM，Need ultrasonic);H2O:< 0.1 mg/mL

ClC1=C([C@H](NC2=C(NC3=NC(OC)=NC(N4CCNCC4)=N3)C=C(S(C)(=O)=O)C=C2)C5=C6OC(F)(OC6=CC=C5)F)N=CC=C1

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(-20℃)

With Ice Pack

≥ 2 years