| MV4-11 |
GI |
|
|
|
Cytotoxicity against human MV4-11 cells harboring MLL-AF4 oncogene assessed as growth inhibition at 1 to 30 uM by XTT assay |
CHEMBL2169812 |
| Histone-lysine N-methyltransferase, H3 lysine-79 specific |
Kd |
= |
66.0 |
nM |
Binding affinity at human recombinant DOT1L catalytic domain amino acid (1 to 472)-nucleosome complex by isothermal titration calorimetric assay |
CHEMBL2169812 |
| Histone-lysine N-methyltransferase, H3 lysine-79 specific |
Kd |
= |
550.0 |
nM |
Competitive inhibition of human recombinant DOT1L catalytic domain amino acid (1 to 472)-nucleosome complex by isothermal titration calorimetric assay in presence of 20 uM of SAH |
CHEMBL2169812 |
| Histone-lysine N-methyltransferase, H3 lysine-79 specific |
Kd |
= |
240.0 |
nM |
Competitive inhibition of human recombinant DOT1L catalytic domain amino acid (1 to 472)-nucleosome complex by isothermal titration calorimetric assay in presence of 10 uM of SAH |
CHEMBL2169812 |
| Histone-lysine N-methyltransferase, H3 lysine-79 specific |
Kd |
= |
200.0 |
nM |
Competitive inhibition of human recombinant DOT1L catalytic domain amino acid (1 to 472)-nucleosome complex by isothermal titration calorimetric assay in presence of 5 uM of SAH |
CHEMBL2169812 |
| Histone-lysine N-methyltransferase, H3 lysine-79 specific |
Kd |
= |
130.0 |
nM |
Competitive inhibition of human recombinant DOT1L catalytic domain amino acid (1 to 472)-nucleosome complex by isothermal titration calorimetric assay in presence of 2.5 uM of SAH |
CHEMBL2169812 |
| Unchecked |
Ratio Ki |
> |
4500.0 |
|
Selectivity ratio of Ki for SUV39H1 to Ki for human recombinant DOT1L catalytic domain amino acid (1 to 472) |
CHEMBL2169812 |
| Unchecked |
Ratio Ki |
> |
4500.0 |
|
Selectivity ratio of Ki for CARM1 to Ki for human recombinant DOT1L catalytic domain amino acid (1 to 472) |
CHEMBL2169812 |
| Unchecked |
Ratio Ki |
> |
4500.0 |
|
Selectivity ratio of Ki for PRMT1 to Ki for human recombinant DOT1L catalytic domain amino acid (1 to 472) |
CHEMBL2169812 |
| Histone-lysine N-methyltransferase, H3 lysine-79 specific |
Kd |
= |
73.0 |
nM |
Competitive inhibition of human recombinant DOT1L catalytic domain amino acid (1 to 472)-nucleosome complex by isothermal titration calorimetric assay in presence of 1 uM of SAH |
CHEMBL2169812 |
| NB-4 |
EC50 |
= |
101000.0 |
nM |
Cytotoxicity against human NB4 cells harboring wild type MLL oncogene after 20 days by XTT assay |
CHEMBL2169812 |
| THP-1 |
EC50 |
= |
8100.0 |
nM |
Cytotoxicity against human THP1 cells harboring MLL-AF9 oncogene after 20 days by XTT assay |
CHEMBL2169812 |
| MV4-11 |
EC50 |
= |
4400.0 |
nM |
Cytotoxicity against human MV4-11 cells harboring MLL-AF4 oncogene after 20 days by XTT assay |
CHEMBL2169812 |
| MV4-11 |
GI |
= |
91.7 |
% |
Cytotoxicity against human MV4-11 cells harboring MLL-AF4 oncogene assessed as growth inhibition at 10 uM measured on day 20 by XTT assay |
CHEMBL2169812 |
| MV4-11 |
GI |
= |
61.7 |
% |
Cytotoxicity against human MV4-11 cells harboring MLL-AF4 oncogene assessed as growth inhibition at 10 uM measured on day 15 by XTT assay |
CHEMBL2169812 |
| Histone-lysine N-methyltransferase SUV39H1 |
Ki |
> |
100000.0 |
nM |
Inhibition of SUV39H1 |
CHEMBL2169812 |
| Histone-arginine methyltransferase CARM1 |
Ki |
> |
100000.0 |
nM |
Inhibition of CARM1 |
CHEMBL2169812 |
| Protein-arginine N-methyltransferase 1 |
Ki |
> |
100000.0 |
nM |
Inhibition of PRMT1 |
CHEMBL2169812 |
| Histone-lysine N-methyltransferase, H3 lysine-79 specific |
Ki |
= |
0.46 |
nM |
Inhibition of human recombinant DOT1L catalytic domain amino acid (1 to 472) using [3H]-SAM after 30 mins by scintillation counter |
CHEMBL2169812 |
| Histone-lysine N-methyltransferase, H3 lysine-79 specific |
Kd |
= |
170.0 |
nM |
Binding affinity at human recombinant DOT1L catalytic domain amino acid (1 to 472) by isothermal titration calorimetric assay |
CHEMBL2169812 |
| MV4-11 |
GI |
|
|
|
Cytotoxicity against human MV4-11 cells harboring MLL-AF4 oncogenes assessed as growth inhibition at 10 uM measured on day 10 |
CHEMBL2169812 |
| THP-1 |
EC50 |
= |
4.0 |
nM |
Antiproliferative activity against human THP1 cells containing MLL-AF9 |
CHEMBL3085656 |
| MV4-11 |
EC50 |
= |
4.0 |
nM |
Antiproliferative activity against human MV4-11 cells containing MLL-AF4 |
CHEMBL3085656 |
| MOLM-13 |
EC50 |
= |
4.0 |
nM |
Antiproliferative activity against human MOLM13 cells containing MLL-AF9 |
CHEMBL3085656 |
| Histone-lysine N-methyltransferase, H3 lysine-79 specific |
Ki |
= |
0.5 |
nM |
Competitive inhibition of recombinant human DOT1L using adenosine/deazaadenosine as substrate and SAM cofactor |
CHEMBL3085656 |
| Liver microsome |
CLH |
= |
24.0 |
uL/min |
Intrinsic clearance in human liver microsomes assessed per mg of protein |
CHEMBL3085656 |
| Histone-lysine N-methyltransferase, H3 lysine-79 specific |
EC50 |
= |
9.0 |
nM |
Inhibition of DOT1L (unknown origin)-mediated H3K79 methylation by cell based assay |
CHEMBL3085656 |
| Liver microsome |
CLH |
= |
24.0 |
uL/min |
Intrinsic clearance in human liver microsomes measured per gram of protein at 200 uM measured after 1 by LC/MS/MS method |
CHEMBL3132754 |
| Liver microsome |
Stability |
= |
50.0 |
% |
Metabolic stability in human liver microsomes assessed as compound remaining at 200 uM measured after 1 hr by LC/MS/MS method |
CHEMBL3132754 |
| Plasma |
Stability |
= |
90.0 |
% |
Stability in human plasma assessed as compound remaining at 5 uM after 1 hr by LC/MS/MS method |
CHEMBL3132754 |
| Histone-lysine N-methyltransferase SUV39H1 |
Ki |
> |
50000.0 |
nM |
Inhibition of SUV39H1 (unknown origin) |
CHEMBL3132754 |
| Histone-lysine N-methyltransferase, H3 lysine-79 specific |
Ki |
= |
0.72 |
nM |
Inhibition of human recombinant DOT1L (catalytic domain 1 to 472) using [3H]-SAM by scintillation containing |
CHEMBL3132754 |
| Histone-arginine methyltransferase CARM1 |
Ki |
> |
50000.0 |
nM |
Inhibition of CARM1 (unknown origin) |
CHEMBL3132754 |
| MV4-11 |
IC50 |
= |
200.0 |
nM |
Induction of histone methylation in human MV4-11 cells assessed as H3K79 methylation after 4 days by Western blot analysis |
CHEMBL3132754 |
| Protein-arginine N-methyltransferase 1 |
Ki |
> |
50000.0 |
nM |
Inhibition of PRMT1 (unknown origin) |
CHEMBL3132754 |
| No relevant target |
LogD7.4 |
|
2.2 |
|
ASTRAZENECA: Octan-1-ol/water (pH7.4) distribution coefficent measured by a shake flask method described in J. Biomol. Screen. 2011, 16, 348-355. Experimental range -1.5 to 4.5 |
CHEMBL3301361 |
| ADMET |
PPB |
|
71.53 |
% |
ASTRAZENECA: % bound to plasma by equilibrium dialysis. Compound is incubated with whole human plasma at 37C for >5hrs. Method described in B. Testa et al (Eds.), Pharmacokinetic Profiling in Drug Research: Biological, Physicochemical, and Computational Strategies, Wiley-VCH, Weinheim, 2006, pp.119-141. Experimental range 10% to 99.95% bound. |
CHEMBL3301361 |
| ADMET |
CL |
|
26.92 |
uL.min-1.(10^6cells)-1 |
ASTRAZENECA: Intrinsic clearance measured in rat hepatocytes following incubation at 37C. Experimental range <3 to >150 microL/min/1E6 cells. Rapid Commun. Mass Spectrom. 2010, 24, 1730-1736 |
CHEMBL3301361 |
| ADMET |
CL |
|
112.2 |
mL.min-1.g-1 |
ASTRAZENECA: Intrinsic clearance measured in human liver microsomes following incubation at 37C. Experimental range <3 to >150 microL/min/mg. Rapid Commun. Mass Spectrom. 2010, 24, 1730-1736. |
CHEMBL3301361 |
| Histone-lysine N-methyltransferase, H3 lysine-79 specific |
IC50 |
= |
100.0 |
nM |
Inhibition of recombinant human N-terminal GST-tagged DOT1L (2 to 416 residues) expressed in Escherichia coli assessed as reduction in histone H3 lysine-N-methyltransferase activity using nucleosomes after 3 hrs in presence of SAM by AlphLisa assay |
CHEMBL4043280 |
| Histone-lysine N-methyltransferase, H3 lysine-79 specific |
IC50 |
= |
14.0 |
nM |
Inhibition of recombinant human His6-SUMO tagged DOT1L (1 to 416 residues) expressed in Escherichia coli BL21(DE3) using oligonucleosome as substrate measured after 30 mins in presence of SAM by AlphaLISA assay |
CHEMBL4219142 |
| Plasmodium falciparum |
Inhibition |
= |
9.7 |
% |
Antiplasmodial activity against asynchronous form of Plasmodium falciparum 3D7 infected in human erythrocytes assessed as parasite growth inhibition at 10 uM after 48 hrs by SYBR green1 staining based flow cytometry relative to control |
CHEMBL4325862 |
| Plasmodium falciparum |
IC50 |
|
|
|
Antiplasmodial activity against asynchronous form of Plasmodium falciparum 3D7 infected in human erythrocytes assessed as parasite growth inhibition after 48 hrs by SYBR green1 staining based flow cytometry |
CHEMBL4325862 |
| DNA (cytosine-5)-methyltransferase 1 |
IC50 |
= |
2.9 |
nM |
Inhibition of DNMT1 (unknown origin) |
CHEMBL4477246 |
