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Compound Detail

CHEMBL3414626

PINOMETOSTAT
🧪 Phase II
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🧪 Phase II
CC(C)N(C[C@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@H](O)[C@@H]1O)[C@H]1C[C@@H](CCc2nc3cc(C(C)(C)C)ccc3[nH]2)C1

Basic Information

ChEMBL ID CHEMBL3414626
Name PINOMETOSTAT
Phase Phase II
Structure Type MOL
InChI Key LXFOLMYKSYSZQS-LURJZOHASA-N

Known Names

EPZ-005676 EPZ-5676 Pinometostat Pinometostat anhydrous
7
Targets
25
Activities
3
Assay Types
14
PK Parameters
20
Publications
4
Known Names
2
Indications

Molecular Properties

562.7
MW (Da)
3.32
ALogP
10
HBA
4
HBD
151.2
PSA (Ų)
0.25
QED
1
Ro5 Violations
8
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Single Enantiomer

Flags

Natural Product
USAN Stem -stat

Extended Properties

Molecular Formula C30H42N8O3
MW 562.72
Aromatic Rings 4
Heavy Atoms 41
NP-Likeness -0.18

Indications

Leukemia, Myeloid, Acute Precursor Cell Lymphoblastic Leukemia-Lymphoma

Activity Summary

IC50 18 meas. best 9.13
EC50 4 meas. best 8.4
Ki 3 meas. best 10.92

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Histone-lysine N-methyltransferase, H3 lysine-79 specific
CHEMBL1795117
Ki 10.92 10.3733 0.0 3
Histone-lysine N-methyltransferase, H3 lysine-79 specific
CHEMBL1795117
IC50 9.13 8.3971 0.7 7
MOLM-13
CHEMBL3706572
EC50 8.4 8.4 4.0 1
MV4-11
CHEMBL613835
EC50 8.4 8.4 4.0 1
THP-1
CHEMBL614245
EC50 8.4 8.4 4.0 1
Histone-lysine N-methyltransferase, H3 lysine-79 specific
CHEMBL1795117
EC50 8.05 8.05 9.0 1
MV4-11
CHEMBL613835
IC50 7.82 7.56 15.0 2
MOLM-13
CHEMBL3706572
IC50 7.68 7.2033 21.0 6
KOPN-8
CHEMBL4296456
IC50 7.22 7.22 60.0 1
RS4-11
CHEMBL2366159
IC50 7.16 7.16 70.0 1
K562
CHEMBL385
IC50 4.51 4.51 31000.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 0.6617 ng.hr.mL-1 Mus musculus
AUC 4833.33 ng.hr.mL-1 Mus musculus
AUC - - Mus musculus
AUC 4866.67 ng.hr.mL-1 Mus musculus
CL 17.1 mL.min-1.kg-1 Mus musculus
Cmax 28.26 nM Mus musculus
Cmax 24701.45 nM Mus musculus
F - % Mus musculus
t1/2 - - Mus musculus
T1/2 0.72 hr Mus musculus
Tmax 0.08333 hr Mus musculus
Tmax 0.08333 hr Mus musculus
Vd - - Mus musculus
Vd 1.07 L.kg-1 Mus musculus

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 = 0.012 nM 10.92 Competitive inhibition of DOT1L (2 to 416 residues) (unknown origin) using bioti... 28337327
Histone-lysine N-methyltransferase, H3 lysine-79 specific Ki = 0.08 nM 10.1 Inhibition of human DOT1-like Histone H3 Methyltransferase preincubated for 30 m... 31188592
Histone-lysine N-methyltransferase, H3 lysine-79 specific Ki = 0.08 nM 10.1 Inhibition of human DOT1L using oligo-nucleosome/[3H]-SAM as substrate preincuba... 25406853
Histone-lysine N-methyltransferase, H3 lysine-79 specific IC50 = 0.74 nM 9.13 In Vitro Biological Assay: An in vitro biological assay that can be used include... -
Histone-lysine N-methyltransferase, H3 lysine-79 specific IC50 = 0.74 nM 9.13 DOT1L IC50: Test compounds were serially diluted 3 fold in DMSO for 10 points an... -
Histone-lysine N-methyltransferase, H3 lysine-79 specific IC50 = 3.0 nM 8.52 Inhibition of DOT1L in human MV4-11 cells expressing MLL-AF4 assessed as reducti... 25406853
Histone-lysine N-methyltransferase, H3 lysine-79 specific IC50 = 3.5 nM 8.46 Inhibition of DOT1L in human MV4-11 cells expressing MLL-AF4 assessed as cell gr... 25406853
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
MV4-11 EC50 = 4.0 nM 8.4 Antiproliferative activity against human MV4-11 cells containing MLL-AF4 23879463
Histone-lysine N-methyltransferase, H3 lysine-79 specific IC50 = 7.0 nM 8.15 Inhibition of DOT1L in human HeLa cells assessed as reduction in H3K79me2 level ... 28337327
Histone-lysine N-methyltransferase, H3 lysine-79 specific IC50 = 7.81 nM 8.11 Inhibition of recombinant human N-terminal GST-tagged DOT1L (2 to 416 residues) ... 29050780
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
MV4-11 IC50 = 15.0 nM 7.82 Antiproliferative activity against human MV4-11 cells harboring MLL-AF4 treated ... 28337327
MOLM-13 IC50 = 21.0 nM 7.68 Anticancer activity against human MOLM-13 cells harbouring MLL-AF9 assessed as i... 35612819
MOLM-13 IC50 = 30.0 nM 7.52 Anticancer activity against human MOLM-13 cells harbouring MLL-AF9 assessed as i... 35612819
MV4-11 IC50 = 50.0 nM 7.3 Anticancer activity against human MV4-11 cells assessed as inhibition of cell gr... 35612819
Histone-lysine N-methyltransferase, H3 lysine-79 specific IC50 = 52.0 nM 7.28 Inhibition of DOT1L in human MOLM13 cells assessed as suppression of HoxA9 gene ... 28337327
MOLM-13 IC50 = 59.0 nM 7.23 Anticancer activity against human MOLM-13 cells harbouring MLL-AF9 assessed as i... 35612819
KOPN-8 IC50 = 60.0 nM 7.22 Anticancer activity against human KOPN-8 cells harbouring MLL-ENL assessed as in... 35612819

Literature References

PubMed DOI Target Context # Activities
35612819 10.1021/acs.jmedchem.2c00083 Unchecked 46
30171029 10.3324/haematol.2018.191262 RPMI-8226 22
30171029 10.3324/haematol.2018.191262 MM1.S 20
35302777 10.1021/acs.jmedchem.1c02228 ADMET 20
25406853 10.1021/jm501234a Unchecked 15
30171029 10.3324/haematol.2018.191262 Unchecked 14
35612819 10.1021/acs.jmedchem.2c00083 MOLM-13 7
35302777 10.1021/acs.jmedchem.1c02228 Histone-lysine N-methyltransferase, H3 lysine-79 specific 6
30171029 10.3324/haematol.2018.191262 KMS-12-PE 6
30171029 10.3324/haematol.2018.191262 KMS-12-BM 5
28337327 10.1021/acsmedchemlett.6b00519 Histone-lysine N-methyltransferase, H3 lysine-79 specific 5
- 10.6019/CHEMBL4495565 SARS-CoV-2 4
33691794 10.1186/s13148-021-01037-1 A549 4
25406853 10.1021/jm501234a Histone-lysine N-methyltransferase, H3 lysine-79 specific 4
30171029 10.3324/haematol.2018.191262 U-266 2
- 10.6019/CHEMBL4495564 Replicase polyprotein 1ab 2
- 10.6019/CHEMBL4808148 Histone deacetylase 6 2
35302777 10.1021/acs.jmedchem.1c02228 OCI-AML-3 2
35302777 10.1021/acs.jmedchem.1c02228 SUD4 2
23879463 10.1021/jm4007752 Histone-lysine N-methyltransferase, H3 lysine-79 specific 2

Data from ChEMBL 36 via Core Engine