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Compound Detail

CHEMBL2171169

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CC(C)N(CCCNC(=O)Nc1ccc(C(C)(C)C)cc1)C[C@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@H](O)[C@@H]1O

Basic Information

ChEMBL ID CHEMBL2171169
Phase Preclinical
Structure Type MOL
InChI Key MTLMDZJUGDUTCP-PTGPVQHPSA-N
6
Targets
25
Activities
4
Assay Types
2
PK Parameters
20
Publications
0
Known Names

Molecular Properties

540.7
MW (Da)
2.25
ALogP
10
HBA
5
HBD
163.7
PSA (Ų)
0.26
QED
1
Ro5 Violations
9
Rot. Bonds

Drug Information

Molecule Type Small molecule
Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula C27H40N8O4
MW 540.67
Aromatic Rings 3
Heavy Atoms 39
NP-Likeness -0.57

Activity Summary

Kd 9 meas. best 8.7
EC50 7 meas. best 8.4
IC50 6 meas. best 8.54
Ki 3 meas. best 9.34

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Histone-lysine N-methyltransferase, H3 lysine-79 specific
CHEMBL1795117
Ki 9.34 9.26 0.5 3
Histone-lysine N-methyltransferase, H3 lysine-79 specific
CHEMBL1795117
Kd 8.7 7.2178 2.0 9
Histone-lysine N-methyltransferase, H3 lysine-79 specific
CHEMBL1795117
IC50 8.54 7.7967 2.9 3
DNA (cytosine-5)-methyltransferase 1
CHEMBL1993
IC50 8.54 8.54 2.9 1
MOLM-13
CHEMBL3706572
EC50 8.4 8.4 4.0 1
MV4-11
CHEMBL613835
EC50 8.4 6.88 4.0 2
THP-1
CHEMBL614245
EC50 8.4 6.745 4.0 2
Histone-lysine N-methyltransferase, H3 lysine-79 specific
CHEMBL1795117
EC50 8.05 8.05 9.0 1
MV4-11
CHEMBL613835
IC50 6.7 6.7 200.0 1
Unchecked
CHEMBL612545
IC50 5.84 5.84 1452.0 1

Pharmacokinetic Data

Parameter Value Units Species
CL 26.92 uL.min-1.(10^6cells)-1 Rattus norvegicus
CL 112.2 mL.min-1.g-1 Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Histone-lysine N-methyltransferase, H3 lysine-79 specific Ki = 0.46 nM 9.34 Inhibition of human recombinant DOT1L catalytic domain amino acid (1 to 472) usi... 22924785
Histone-lysine N-methyltransferase, H3 lysine-79 specific Ki = 0.5 nM 9.3 Competitive inhibition of recombinant human DOT1L using adenosine/deazaadenosine... 23879463
Histone-lysine N-methyltransferase, H3 lysine-79 specific Ki = 0.72 nM 9.14 Inhibition of human recombinant DOT1L (catalytic domain 1 to 472) using [3H]-SAM... 23795283
Histone-lysine N-methyltransferase, H3 lysine-79 specific Kd = 1.99 nM 8.7 Binding affinity to recombinant N-terminal DOT1L (1 to 420 residues) (unknown or... 23250418
Histone-lysine N-methyltransferase, H3 lysine-79 specific Kd = 1.99 nM 8.7 Binding affinity to recombinant N-terminal DOT1L (1 to 420 residues) (unknown or... 23250418
DNA (cytosine-5)-methyltransferase 1 IC50 = 2.9 nM 8.54 Inhibition of DNMT1 (unknown origin) 27485386
Histone-lysine N-methyltransferase, H3 lysine-79 specific IC50 = 2.9 nM 8.54 Inhibition of recombinant N-terminal DOT1L (1 to 420 residues) (unknown origin) ... 23250418
MV4-11 EC50 = 4.0 nM 8.4 Antiproliferative activity against human MV4-11 cells containing MLL-AF4 23879463
MOLM-13 EC50 = 4.0 nM 8.4 Antiproliferative activity against human MOLM13 cells containing MLL-AF9 23879463
THP-1 EC50 = 4.0 nM 8.4 Antiproliferative activity against human THP1 cells containing MLL-AF9 23879463
Histone-lysine N-methyltransferase, H3 lysine-79 specific EC50 = 9.0 nM 8.05 Inhibition of DOT1L (unknown origin)-mediated H3K79 methylation by cell based as... 23879463
Histone-lysine N-methyltransferase, H3 lysine-79 specific IC50 = 14.0 nM 7.85 Inhibition of recombinant human His6-SUMO tagged DOT1L (1 to 416 residues) expre... 29534934
Histone-lysine N-methyltransferase, H3 lysine-79 specific Kd = 66.0 nM 7.18 Binding affinity at human recombinant DOT1L catalytic domain amino acid (1 to 47... 22924785
Histone-lysine N-methyltransferase, H3 lysine-79 specific Kd = 73.0 nM 7.14 Competitive inhibition of human recombinant DOT1L catalytic domain amino acid (1... 22924785
Histone-lysine N-methyltransferase, H3 lysine-79 specific IC50 = 100.0 nM 7.0 Inhibition of recombinant human N-terminal GST-tagged DOT1L (2 to 416 residues) ... 29050780
Histone-lysine N-methyltransferase, H3 lysine-79 specific Kd = 130.0 nM 6.89 Competitive inhibition of human recombinant DOT1L catalytic domain amino acid (1... 22924785
Histone-lysine N-methyltransferase, H3 lysine-79 specific Kd = 170.0 nM 6.77 Binding affinity at human recombinant DOT1L catalytic domain amino acid (1 to 47... 22924785
MV4-11 IC50 = 200.0 nM 6.7 Induction of histone methylation in human MV4-11 cells assessed as H3K79 methyla... 23795283
Histone-lysine N-methyltransferase, H3 lysine-79 specific Kd = 200.0 nM 6.7 Competitive inhibition of human recombinant DOT1L catalytic domain amino acid (1... 22924785
Histone-lysine N-methyltransferase, H3 lysine-79 specific Kd = 240.0 nM 6.62 Competitive inhibition of human recombinant DOT1L catalytic domain amino acid (1... 22924785

Literature References

PubMed DOI Target Context # Activities
22924785 10.1021/jm300917h Histone-lysine N-methyltransferase, H3 lysine-79 specific 8
22924785 10.1021/jm300917h MV4-11 5
23250418 10.1038/ncomms2304 Histone-lysine N-methyltransferase, H3 lysine-79 specific 5
- 10.6019/CHEMBL3301361 ADMET 3
22924785 10.1021/jm300917h Unchecked 3
30366254 10.1016/j.ejmech.2018.10.041 Plasmodium falciparum 2
23250418 10.1038/ncomms2304 Unchecked 2
23879463 10.1021/jm4007752 Histone-lysine N-methyltransferase, H3 lysine-79 specific 2
23795283 10.1039/c3md00021d Liver microsome 2
23879463 10.1021/jm4007752 Liver microsome 1
23795283 10.1039/c3md00021d MV4-11 1
23795283 10.1039/c3md00021d Histone-arginine methyltransferase CARM1 1
22924785 10.1021/jm300917h NB-4 1
23795283 10.1039/c3md00021d Histone-lysine N-methyltransferase SUV39H1 1
23795283 10.1039/c3md00021d Plasma 1
22924785 10.1021/jm300917h THP-1 1
23879463 10.1021/jm4007752 MOLM-13 1
23879463 10.1021/jm4007752 THP-1 1
22924785 10.1021/jm300917h Protein arginine N-methyltransferase 1 1
22924785 10.1021/jm300917h Histone-arginine methyltransferase CARM1 1

Data from ChEMBL 36 via Core Engine