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Compound Detail

CHEMBL4297463

CPI-1205
Phase I
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Phase I
COc1cc(C)[nH]c(=O)c1CNC(=O)c1c(C)n([C@H](C)C2CCN(CC(F)(F)F)CC2)c2ccccc12

Basic Information

ChEMBL ID CHEMBL4297463
Name CPI-1205
Phase Phase I
Structure Type MOL
InChI Key HPODOLXTMDHLLC-QGZVFWFLSA-N

Known Names

Cpi-1205 Ezh2 inhibitor cpi-1205 Lirametostat
3
Targets
11
Activities
2
Assay Types
26
PK Parameters
20
Publications
3
Known Names
3
Indications

Molecular Properties

518.6
MW (Da)
4.72
ALogP
5
HBA
2
HBD
79.4
PSA (Ų)
0.47
QED
1
Ro5 Violations
7
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Single Enantiomer

Flags

Chemical Probe

Extended Properties

Molecular Formula C27H33F3N4O3
MW 518.58
Aromatic Rings 3
Heavy Atoms 37
NP-Likeness -1.16

Indications

Lymphoma, Follicular Neoplasms Prostatic Neoplasms, Castration-Resistant

Activity Summary

IC50 9 meas. best 8.7
EC50 2 meas. best 7.55

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Histone-lysine N-methyltransferase EZH2
CHEMBL2189110
IC50 8.7 7.9614 2.0 7
Histone-lysine N-methyltransferase EZH2
CHEMBL2189110
EC50 7.55 7.525 28.0 2
Histone-lysine N-methyltransferase EZH1
CHEMBL2189116
IC50 7.28 7.28 52.0 1
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
IC50 4.67 4.67 21300.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 46091.39 ng.hr.mL-1 Mus musculus
AUC 3661.17 ng.hr.mL-1 Rattus norvegicus
AUC 1654.27 ng.hr.mL-1 Canis lupus familiaris
CL 23.5 mL.min-1.kg-1 Canis lupus familiaris
CL 241.67 mL.min-1.kg-1 Canis lupus familiaris
CL 97.0 % Rattus norvegicus
CL 36.0 mL.min-1.kg-1 Mus musculus
CL 1715.0 mL.min-1.kg-1 Mus musculus
CL 40.0 % Mus musculus
CL 53.17 mL.min-1.kg-1 Rattus norvegicus
CL 526.67 mL.min-1.kg-1 Rattus norvegicus
CL 76.0 % Canis lupus familiaris
Cmax 67360.0 nM Mus musculus
Cmax 5880.0 nM Rattus norvegicus
Cmax 1240.0 nM Canis lupus familiaris
F 100.0 % Mus musculus
F 44.6 % Rattus norvegicus
F 46.2 % Canis lupus familiaris
Fu 0.00021 - Mus musculus
Fu 0.00022 - Rattus norvegicus
Fu 0.00021 - Canis lupus familiaris
T1/2 1.63 hr Mus musculus
T1/2 0.653 hr Rattus norvegicus
T1/2 1.84 hr Canis lupus familiaris
Tmax 0.5 hr Rattus norvegicus
Tmax 1.67 hr Canis lupus familiaris

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Histone-lysine N-methyltransferase EZH2 IC50 = 2.0 nM 8.7 Affinity Biochemical interaction: (Scintillation proximity assay) EUB0002212a EZ... -
Histone-lysine N-methyltransferase EZH2 IC50 = 2.2 nM 8.66 Inhibition of wild-type EZH2 in PRC2 complex (unknown origin) using RKQLATKAARK(... 27739677
Histone-lysine N-methyltransferase EZH2 IC50 = 3.1 nM 8.51 Inhibition of EZH2 Y641F mutant in PRC2 complex (unknown origin) using RKQLATKAA... 27739677
Histone-lysine N-methyltransferase EZH2 IC50 = 22.0 nM 7.66 Inhibition of EZH2 Y641F mutant (unknown origin) 35531606
Histone-lysine N-methyltransferase EZH2 EC50 = 28.0 nM 7.55 Inhibition of EZH2 in human HeLa cells assessed as inhibition of trimethylation ... 32551002
Histone-lysine N-methyltransferase EZH2 IC50 = 31.0 nM 7.51 Inhibition of wild-type EZH2 (unknown origin) 35531606
Histone-lysine N-methyltransferase EZH2 EC50 = 32.0 nM 7.5 Inhibition of EZH2 in human HeLa cells assessed as inhibition of trimethylation ... 27739677
Histone-lysine N-methyltransferase EZH2 IC50 = 32.0 nM 7.5 Inhibition of EZH2 in human HeLa cells assessed as reduction in H3K27-me3 level ... 38762915
Histone-lysine N-methyltransferase EZH1 IC50 = 52.0 nM 7.28 Inhibition of EZH1 (unknown origin) 27739677
Histone-lysine N-methyltransferase EZH2 IC50 = 64.0 nM 7.19 Inhibition of EZH2 (unknown origin) 38056296
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 21300.0 nM 4.67 Binding affinity to human ERG 27739677

Literature References

PubMed DOI Target Context # Activities
27739677 10.1021/acs.jmedchem.6b01315 ADMET 46
27739677 10.1021/acs.jmedchem.6b01315 Histone-lysine N-methyltransferase EZH2 3
27739677 10.1021/acs.jmedchem.6b01315 Cytochrome P450 2C9 2
- 10.6019/CHEMBL5724709 Fibroblast 2
- 10.6019/CHEMBL5724709 U2OS 2
- 10.6019/CHEMBL5724709 HEK-293T 2
35531606 10.1021/acs.jmedchem.2c00047 Histone-lysine N-methyltransferase EZH2 2
32551002 10.1021/acsmedchemlett.0c00045 Histone-lysine N-methyltransferase EZH2 2
27739677 10.1021/acs.jmedchem.6b01315 Cytochrome P450 1A2 2
27739677 10.1021/acs.jmedchem.6b01315 Cytochrome P450 2C8 2
27739677 10.1021/acs.jmedchem.6b01315 Cytochrome P450 2D6 2
27739677 10.1021/acs.jmedchem.6b01315 Cytochrome P450 3A4 2
27739677 10.1021/acs.jmedchem.6b01315 KARPAS-422 2
- 10.6019/CHEMBL4651402 SARS-CoV-2 2
27739677 10.1021/acs.jmedchem.6b01315 Unchecked 1
27739677 10.1021/acs.jmedchem.6b01315 Histone-lysine N-methyltransferase EZH1 1
27739677 10.1021/acs.jmedchem.6b01315 Voltage-gated inwardly rectifying potassium channel KCNH2 1
38056296 10.1016/j.ejmech.2023.115982 Histone-lysine N-methyltransferase EZH2 1
38762915 10.1016/j.ejmech.2024.116470 Histone-lysine N-methyltransferase EZH2 1
- 10.6019/CHEMBL5724796 Bromodomain-containing protein 4 1

Data from ChEMBL 36 via Core Engine