dot1l-in-1

The Ki value of DOT1L-in-1 is 2pm.It is a highly effective, selective and novel Dot1L inhibitor.

Dot1L-IN-1 TFA is a potent and selective Dot1L inhibitor, with a K i of 2 pM and an IC50 of <0.1 nM. It effectively inhibits H3K79 dimethylation (IC50 = 3 nM) and suppresses HoxA9 promoter activity (IC50 = 17 nM) in HeLa and Molm-13 cells, respectively [1].

TC-5115 is a highly potent, selective inhibitor of the SET domain of the histone lysine methyltransferase MLL1 (KMT2A), with an IC₅₀ value of 16 nM. TC-5115 exhibits weak inhibitory activity against other methyltransferases such as SET7/9, DOT1L, and EZH2 (IC₅₀ > 1 μM). TC-5115 induces differentiation and growth arrest in leukemia cells and can be used in leukemia research.

Dot1L-IN-8 (Compound 15) is an effective Dot1L inhibitor. It suppresses the viability of HL-60, K562, MV4-11, HH, and KG-1 cells, with IC50 values of 0.45, 1.03, 0.68, 1.66, and 1.12 μM, respectively.

S-N6-Methyladenosylhomocysteine (Chart 1-1) is a potent inhibitor of the histone methyltransferase DOT1L, with an IC50 of 0.29 μM. This compound plays a significant role in cancer research.

DOT1Lligand-1 is a ligand for DOT1L. It serves as a ligand for target proteins (Ligands for Target Protein for PROTAC) and is utilized in the synthesis of PROTACs targeting DOT1L, such as MS2133.

MS2133 is a DOT1L PROTAC degrader. It facilitates the ubiquitination and degradation of DOT1L in THP-1 and MV4-11 cells, with DC50 values of 56 nM and 25 nM, respectively, and reduces H3K79 methylation. MS2133 also inhibits the growth of MLL-r leukemia cells, demonstrating anticancer activity.

Thalidomide-O-amido-C11-COOH (Compound IMiD acid 1) is a compound that acts as an E3 ligase ligand and linker for the CRBN (Cereblon) conjugate. This compound is useful in synthesizing PROTACs targeting the degradation of DOT1L.

AF9/ENL-DOT1L/AF4 PPI-IN-1 is a potent inhibitor of protein-protein interactions (PPI) between AF9/ENL and the histone methyltransferase DOT1L/AF4. It effectively inhibits the interactions of AF9-DOT1L (IC50= 1.5 μM), AF9-AF4 (IC50= 1 μM), and ENL-AF4 (IC50= 1.2 μM). This compound suppresses the expression of MLL target genes, Myc and Meis1, and selectively blocks the proliferation of MLL-r and other leukemia cells. In a mouse model of MLL-r leukemia, AF9/ENL-DOT1L/AF4 PPI-IN-1 demonstrates significant antitumor activity with no notable toxicity. It is a useful agent for studying MLL-r leukemia.

Dot1L-IN-7 (compound 25) is a selective and potent inhibitor of telomere silencing 1-like protein (DOT1L) with an IC50 of 1.0 μM. It selectively kills MLL-AF9 cells without affecting the growth of E2A-HLF cells.