Skip to main content
Free research Free research Free compound review with research home and workspace preview
Quick search ChEMBL 36
Compound Detail

CHEMBL3651966

LGH-447
Phase I
Enter ChEMBL ID:
Free Research Context This compound will appear in recent viewed items on the research home for this browser.
Research home View demo workspace
Phase I
C[C@@H]1C[C@H](N)C[C@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cccc3F)n2)C1
ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID CHEMBL3651966
Name LGH-447
Phase Phase I
Structure Type MOL
InChI Key VRQXRVAKPDCRCI-ZNMIVQPWSA-N

Known Names

Lgh-447 LGH447 NVP-LGH477 PIM 447 Pim kinase inhibitor lgh447 PIM-447 PIM447
10
Targets
30
Activities
3
Assay Types
18
PK Parameters
20
Publications
7
Known Names
3
Indications
1
Mechanisms

Molecular Properties

440.5
MW (Da)
5.04
ALogP
4
HBA
2
HBD
80.9
PSA (Ų)
0.60
QED
1
Ro5 Violations
4
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Single Enantiomer

Flags

Chemical Probe

Extended Properties

Molecular Formula C24H23F3N4O
MW 440.47
Aromatic Rings 3
Heavy Atoms 32
NP-Likeness -0.64

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Serine/threonine-protein kinase PIM inhibitor INHIBITOR Serine/threonine-protein kinase PIM ✓ ✓

Indications

Leukemia, Myeloid, Acute Multiple Myeloma Primary Myelofibrosis

Activity Summary

IC50 17 meas. best 10.74
EC50 7 meas. best 6.77
Ki 6 meas. best 10.74

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Serine/threonine-protein kinase pim-2
CHEMBL4523
 IC50 10.74 8.73 0.0 3
Serine/threonine-protein kinase pim-2
CHEMBL4523
 Ki 10.74 10.74 0.0 2
Serine/threonine-protein kinase pim-1
CHEMBL2147
 IC50 9.0 7.69 1.0 4
Serine/threonine-protein kinase pim-3
CHEMBL5407
 IC50 8.7 7.8267 2.0 3
Serine/threonine-protein kinase pim-1
CHEMBL2147
 EC50 6.77 6.77 170.0 1
NON-PROTEIN TARGET
CHEMBL3879801
 EC50 6.77 6.77 170.0 2
KMS-11
CHEMBL4296454
 EC50 6.77 6.77 170.0 1
Serine/threonine-protein kinase pim-2
CHEMBL4523
 EC50 6.77 6.77 170.0 1
Serine/threonine-protein kinase pim-3
CHEMBL5407
 EC50 6.77 6.77 170.0 1
Unchecked
CHEMBL612545
 EC50 6.75 6.75 180.0 1
Glycogen synthase kinase-3 beta
CHEMBL262
 IC50 5.89 5.89 1300.0 1
Protein kinase C theta type
CHEMBL3920
 IC50 5.39 5.39 4100.0 1
Serine/threonine-protein kinase N1
CHEMBL3384
 IC50 5.31 5.31 4900.0 1
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
 IC50 4.92 4.92 12000.0 1

Pharmacokinetic Data

Parameter Value Units Species
CL 28.0 mL.min-1.kg-1 Rattus norvegicus
CL 9.0 mL.min-1.kg-1 Homo sapiens
CL 12.0 mL.min-1.kg-1 Rattus norvegicus
CL 3.0 mL.min-1.kg-1 Homo sapiens
CL 20.0 mL.min-1.kg-1 Mus musculus
CL 28.0 mL.min-1.kg-1 Rattus norvegicus
CL 8.0 mL.min-1.kg-1 Canis lupus familiaris
CL 28.0 mL.min-1.kg-1 Rattus norvegicus
CL 13.0 mL.min-1.kg-1 Homo sapiens
F 84.0 % Mus musculus
F 70.0 % Rattus norvegicus
F 71.0 % Canis lupus familiaris
T1/2 0.8333 hr Rattus norvegicus
T1/2 1.767 hr Homo sapiens
T1/2 3.3 hr Mus musculus
T1/2 2.8 hr Rattus norvegicus
T1/2 6.7 hr Canis lupus familiaris
T1/2 1.767 hr Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Serine/threonine-protein kinase pim-2 Ki = 0.018 nM 10.74 Affinity Biochemical interaction: (AlphaScreen assay (500 uM ATP)) EUB0001581a P... -
Serine/threonine-protein kinase pim-2 Ki = 0.018 nM 10.74 Inhibition of PIM2 kinase (unknown origin) using Biotin-AGAGRSRHSSYPAGT-OH as su... 26505898
Serine/threonine-protein kinase pim-2 IC50 = 0.018 nM 10.74 Inhibition of PIM2 (unknown origin) 30530193
Serine/threonine-protein kinase pim-1 IC50 = 1.0 nM 9.0 ATP Depletion Assay: The activity of PIM1, PIM2, and PIM3 is measured using a lu... -
Serine/threonine-protein kinase pim-2 IC50 = 2.0 nM 8.7 ATP Depletion Assay: The activity of PIM1, PIM2, and PIM3 is measured using a lu... -
Serine/threonine-protein kinase pim-3 IC50 = 2.0 nM 8.7 ATP Depletion Assay: The activity of PIM1, PIM2, and PIM3 is measured using a lu... -
Serine/threonine-protein kinase pim-1 IC50 = 5.8 nM 8.24 Inhibition of PIM1 (unknown origin) 38164076
Serine/threonine-protein kinase pim-3 IC50 = 9.3 nM 8.03 Inhibition of PIM3 (unknown origin) 38164076
Serine/threonine-protein kinase pim-2 EC50 = 170.0 nM 6.77 Affinity Phenotypic Cellular interaction: (Cell Titer-Gloxc2xae assay (prolifera... -
Serine/threonine-protein kinase pim-1 EC50 = 170.0 nM 6.77 Affinity Phenotypic Cellular interaction: (Cell Titer-Gloxc2xae assay (prolifera... -
Serine/threonine-protein kinase pim-3 EC50 = 170.0 nM 6.77 Affinity Phenotypic Cellular interaction: (Cell Titer-Gloxc2xae assay (prolifera... -
NON-PROTEIN TARGET EC50 = 170.0 nM 6.77 Antiproliferative activity against luciferase expressing human KMS11 cells after... 26505898
Serine/threonine-protein kinase pim-1 IC50 = 170.0 nM 6.77 Inhibition of N-terminal 6His-tagged human PIM-1 (29 to 313 residues) expressed ... 38071792
KMS-11 EC50 = 170.0 nM 6.77 Antiproliferative activity against human KMS-11 cells expressing firefly lucifer... 33258605
NON-PROTEIN TARGET EC50 = 170.0 nM 6.77 Antiproliferative activity against human KMS11 expressing luciferase gene after ... 26995528
Unchecked EC50 = 180.0 nM 6.75 Inhibition of PIM kinase in luciferase expressing human KMS11 cells assessed as ... 26505898
Serine/threonine-protein kinase pim-3 IC50 = 180.0 nM 6.75 Affinity Phenotypic Cellular interaction: (Cell Titer-Gloxc2xae assay (prolifera... -
Serine/threonine-protein kinase pim-1 IC50 = 180.0 nM 6.75 Affinity Phenotypic Cellular interaction: (Cell Titer-Gloxc2xae assay (prolifera... -
Serine/threonine-protein kinase pim-2 IC50 = 180.0 nM 6.75 Affinity Phenotypic Cellular interaction: (Cell Titer-Gloxc2xae assay (prolifera... -
Glycogen synthase kinase-3 beta IC50 = 1300.0 nM 5.89 Inhibition of GSK3beta (unknown origin) 26505898

Literature References

PubMed DOI Target Context # Activities
- 10.6019/CHEMBL5444388 Serine/threonine-protein kinase pim-3 28
- 10.6019/CHEMBL5444388 Serine/threonine-protein kinase pim-1 28
- 10.6019/CHEMBL5444388 Serine/threonine-protein kinase pim-2 28
26505898 10.1021/acs.jmedchem.5b01275 NON-PROTEIN TARGET 27
- 10.6019/CHEMBL5465560 Tyrosine-protein kinase ABL1 15
- 10.6019/CHEMBL5465560 Epidermal growth factor receptor 12
- 10.6019/CHEMBL5465560 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform 10
- 10.6019/CHEMBL5303304 Fibroblast 8
26505898 10.1021/acs.jmedchem.5b01275 Mus musculus 8
- 10.6019/CHEMBL5303304 HEK-293T 8
- 10.6019/CHEMBL5465560 Mast/stem cell growth factor receptor Kit 8
- 10.6019/CHEMBL5465560 Receptor-type tyrosine-protein kinase FLT3 7
33258605 10.1021/acs.jmedchem.0c01279 ADMET 6
26505898 10.1021/acs.jmedchem.5b01275 Liver microsome 6
26505898 10.1021/acs.jmedchem.5b01275 Unchecked 6
- 10.6019/CHEMBL5303304 U2OS 5
26505898 10.1021/acs.jmedchem.5b01275 No relevant target 5
26505898 10.1021/acs.jmedchem.5b01275 Canis familiaris 5
26505898 10.1021/acs.jmedchem.5b01275 Rattus norvegicus 4
- 10.6019/CHEMBL5465560 Proto-oncogene tyrosine-protein kinase receptor Ret 4

Data from ChEMBL 36 via Core Engine