Dot1L-IN-5 是强效的类端粒沉默干扰体 1 (DOT1L) 抑制剂，IC50 SPA DOT1L为 0.17 nM。

Dot1L-IN-5 is a potent inhibitor of the disruptor of telomeric silencing 1-like protein ( DOT1L ) with an IC 50 SPA DOT1L of 0.17 nM [1].

Dot1L-IN-5 (Compound 11) is tested in cellular assays in order to assess the ability to inhibit the dimethylation of H3K79 in HeLa cells (ED 50 H3K79me2 Elisa =2.9 nM) and HOXA9 gene expression in Molm-13 cells (ED 50 HOXA9 RGA =30 nM) [1].

Dot1L-IN-5 (Compound 11; subcutaneous injection; at 75 mg/kg once daily for 20 days) does not lead to tumor growth inhibition in NOD-SCID mice. Dot1L-IN-5 (subcutaneous injection; at 75 mg/kg twice daily for 20 days) leads 73% growth inhibition [1]. While both treatment regimens cause very strong inhibition of global H3K79 dimethylation level in tumor, the efficacious regimen is superior in reducing the mRNA expression of the target genes HOXA9 and MEIS1 [1]. Animal Model: NOD-SCID mice bearing subcutaneous MV4-11 tumor xenografts [1] Dosage: 75 mg/kg Administration: Subcutaneous injection; at 75 mg/kg once or twice daily for 20 days Result: Once daily administration did not lead to tumor growth inhibition, 73% growth inhibition was measured in the twice daily treated group.

2565705-03-3

C23H19ClF2N8O5S

592.96

Dot1L-IN-5

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years