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Compound Detail

CHEMBL5403690

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CC(C)(O)CC(=O)N1CCc2cc(Nc3ncc(C(F)(F)F)c(N[C@H]4CC[C@@H](N)CC4)n3)ccc2C1

Basic Information

ChEMBL ID CHEMBL5403690
Phase Preclinical
Structure Type MOL
InChI Key LHDKPFSHXFFALR-HDICACEKSA-N
11
Targets
11
Activities
1
Assay Types
6
PK Parameters
20
Publications
0
Known Names

Molecular Properties

506.6
MW (Da)
3.97
ALogP
7
HBA
4
HBD
116.4
PSA (Ų)
0.47
QED
1
Ro5 Violations
6
Rot. Bonds

Drug Information

Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula C25H33F3N6O2
MW 506.57
Aromatic Rings 2
Heavy Atoms 36
NP-Likeness -1.11

Activity Summary

IC50 11 meas. best 9.68

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
MV4-11
CHEMBL613835
IC50 9.68 9.68 0.2 1
Receptor-type tyrosine-protein kinase FLT3
CHEMBL1974
IC50 8.97 8.97 1.1 1
BaF3
CHEMBL614524
IC50 8.09 8.09 8.2 1
Serine/threonine-protein kinase Chk1
CHEMBL4630
IC50 8.01 8.01 9.8 1
AMPK alpha2/beta1/gamma1
CHEMBL3038455
IC50 7.74 7.74 18.4 1
Mitogen-activated protein kinase kinase kinase 7
CHEMBL5776
IC50 7.19 7.19 64.3 1
Ribosomal protein S6 kinase beta-1
CHEMBL4501
IC50 7.04 7.04 91.6 1
Z-138
CHEMBL4483276
IC50 6.94 6.94 115.0 1
JeKo-1
CHEMBL4296445
IC50 6.58 6.58 260.0 1
Mast/stem cell growth factor receptor Kit
CHEMBL1936
IC50 5.73 5.73 1874.0 1
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
IC50 4.23 4.23 58400.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 1565.74 ng.hr.mL-1 Mus musculus
AUC 1662.69 ng.hr.mL-1 Mus musculus
Cmax 1127.19 nM Mus musculus
MRT 5.73 hr Mus musculus
T1/2 5.6 hr Mus musculus
Tmax 2.0 hr Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
MV4-11 IC50 = 0.21 nM 9.68 Antiproliferative activity against human MV4-11 cells assessed as reduction in c... 37584545
Receptor-type tyrosine-protein kinase FLT3 IC50 = 1.08 nM 8.97 Inhibition of FLT3 D835Y mutant (unknown origin) using peptide substrate TK-S an... 37584545
BaF3 IC50 = 8.2 nM 8.09 Antiproliferative activity against mouse BaF3 cells harboring FLT3-ITD-N701K mut... 37584545
Serine/threonine-protein kinase Chk1 IC50 = 9.8 nM 8.01 Inhibition of CHK1 (unknown origin) using peptide substrate S1 and ATP as substr... 37584545
AMPK alpha2/beta1/gamma1 IC50 = 18.39 nM 7.74 Inhibition of AMPK alpha2beta1gamma1 (unknown origin) by HTRF assay 37584545
Mitogen-activated protein kinase kinase kinase 7 IC50 = 64.32 nM 7.19 Inhibition of TAK1 (unknown origin) by HTRF assay 37584545
Ribosomal protein S6 kinase beta-1 IC50 = 91.62 nM 7.04 Inhibition of P70S6K (unknown origin) by HTRF assay 37584545
Z-138 IC50 = 115.0 nM 6.94 Antiproliferative activity against human Z138 cells assessed as reduction in cel... 37584545
JeKo-1 IC50 = 260.0 nM 6.58 Antiproliferative activity against human JeKo-1 cells assessed as reduction in c... 37584545
Mast/stem cell growth factor receptor Kit IC50 = 1874.0 nM 5.73 Inhibition of c-KIT (unknown origin) using peptide substrate TK-S and ATP as sub... 37584545
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 58400.0 nM 4.23 Inhibition of hERG expressed in HEK293 cells assessed as inhibition of channel c... 37584545

Literature References

PubMed DOI Target Context # Activities
37584545 10.1021/acs.jmedchem.3c00245 Unchecked 25
37584545 10.1021/acs.jmedchem.3c00245 ADMET 15
37584545 10.1021/acs.jmedchem.3c00245 Receptor-type tyrosine-protein kinase FLT3 10
37584545 10.1021/acs.jmedchem.3c00245 MV4-11 6
37584545 10.1021/acs.jmedchem.3c00245 Serine/threonine-protein kinase Chk1 5
37584545 10.1021/acs.jmedchem.3c00245 Voltage-gated inwardly rectifying potassium channel KCNH2 5
37584545 10.1021/acs.jmedchem.3c00245 BaF3 4
37584545 10.1021/acs.jmedchem.3c00245 MOLM-13 3
37584545 10.1021/acs.jmedchem.3c00245 PBMC 1
37584545 10.1021/acs.jmedchem.3c00245 WI-38 1
37584545 10.1021/acs.jmedchem.3c00245 Rec1 1
37584545 10.1021/acs.jmedchem.3c00245 MM1.S 1
37584545 10.1021/acs.jmedchem.3c00245 JeKo-1 1
37584545 10.1021/acs.jmedchem.3c00245 Z-138 1
37584545 10.1021/acs.jmedchem.3c00245 Casein kinase I isoform alpha 1
37584545 10.1021/acs.jmedchem.3c00245 Hepatocyte growth factor receptor 1
37584545 10.1021/acs.jmedchem.3c00245 Ribosomal protein S6 kinase beta-1 1
37584545 10.1021/acs.jmedchem.3c00245 Mitogen-activated protein kinase kinase kinase 7 1
37584545 10.1021/acs.jmedchem.3c00245 AMPK alpha2/beta1/gamma1 1
37584545 10.1021/acs.jmedchem.3c00245 Mast/stem cell growth factor receptor Kit 1

Data from ChEMBL 36 via Core Engine