For research use only. Not for therapeutic Use.
Dot1L-IN-5 is a potent disruptor of telomeric silencing 1-like protein (DOT1L) inhibitor with an IC50 of 0.17 nM[1].
Dot1L-IN-5 (Compound 11) is tested in cellular assays to assess the ability to inhibit the dimethylation of H3K79 in HeLa cells (ED50 H3K79me2 Elisa=2.9 nM) and HOXA9 gene expression in Molm-13 cells (ED50 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 result in 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].
| Catalog Number | I046035 |
| CAS Number | 2565705-03-3 |
| Synonyms | 3-[(4-amino-6-methoxy-1,3,5-triazin-2-yl)amino]-4-[[(S)-(3-chloropyridin-2-yl)-(2,2-difluoro-1,3-benzodioxol-4-yl)methyl]amino]benzenesulfonamide |
| Molecular Formula | C23H19ClF2N8O5S |
| Purity | ≥95% |
| InChI | InChI=1S/C23H19ClF2N8O5S/c1-37-22-33-20(27)32-21(34-22)31-15-10-11(40(28,35)36)7-8-14(15)30-17(18-13(24)5-3-9-29-18)12-4-2-6-16-19(12)39-23(25,26)38-16/h2-10,17,30H,1H3,(H2,28,35,36)(H3,27,31,32,33,34)/t17-/m0/s1 |
| InChIKey | BAQOPDGRUNKWLM-KRWDZBQOSA-N |
| SMILES | COC1=NC(=NC(=N1)NC2=C(C=CC(=C2)S(=O)(=O)N)NC(C3=C4C(=CC=C3)OC(O4)(F)F)C5=C(C=CC=N5)Cl)N |
| Reference | [1]. Frédéric Stauffer, et al. New Potent DOT1L Inhibitors for in Vivo Evaluation in Mouse. ACS Med. Chem. Lett. 2019, 10, 12, 1655-1660. |
