Dot1L-IN-4 (C09-1126-030)

Dot1L-IN-4 is a potent disruptor of telomeric silencing 1-like protein ( DOT1L ) inhibitor with an IC 50 SPA DOT1L of 0.11 nMIn VitroDot1L-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 VivoDot1L-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.Form:SolidIC50& Target:DOT1L 0.11 nM (IC 50 ). Specification: 0.99 Molecular Formula: C28H27ClF2N8O5S Molecular Weight: 661.08 PubChem CID: 145704695 Isomeric SMILES: COC1=NC(=NC(=N1)N2CCNCC2)NC3=C(C=CC(=C3)S(=O)(=O)C)N[C@@H](C4=C5C(=CC=C4)OC(O5)(F)F)C6=C(C=CC=N6)Cl