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Compound Detail

CHEMBL3648680

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Cn1ncc(NC(=O)c2nc(-c3c(F)cccc3F)sc2N)c1N1CC[C@@H](N)[C@H](F)CC1

Basic Information

ChEMBL ID CHEMBL3648680
Phase Preclinical
Structure Type MOL
InChI Key NHXVGMQFCYBLTL-ZWNOBZJWSA-N
12
Targets
18
Activities
2
Assay Types
22
PK Parameters
20
Publications
0
Known Names

Molecular Properties

465.5
MW (Da)
2.92
ALogP
8
HBA
3
HBD
115.1
PSA (Ų)
0.55
QED
0
Ro5 Violations
4
Rot. Bonds

Drug Information

Molecule Type Small molecule
Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula C20H22F3N7OS
MW 465.51
Aromatic Rings 3
Heavy Atoms 32
NP-Likeness -1.44

Activity Summary

IC50 13 meas. best 7.52
Ki 5 meas. best 10.7

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Serine/threonine-protein kinase pim-3
CHEMBL5407
Ki 10.7 10.7 0.0 1
Serine/threonine-protein kinase pim-1
CHEMBL2147
Ki 10.52 10.46 0.0 2
Serine/threonine-protein kinase pim-2
CHEMBL4523
Ki 10.0 10.0 0.1 1
MM1.S
CHEMBL4296471
IC50 7.52 7.34 30.0 2
Dopamine receptor
CHEMBL2096905
IC50 6.3 6.3 500.0 1
Cytochrome P450 3A4
CHEMBL340
Ki 5.95 5.95 1120.0 1
5-hydroxytryptamine receptor 1A
CHEMBL214
IC50 5.6 5.455 2500.0 2
Alpha-1A adrenergic receptor
CHEMBL229
IC50 5.6 5.6 2500.0 1
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
IC50 5.57 5.57 2700.0 1
Mitogen-activated protein kinase kinase kinase kinase 4
CHEMBL6166
IC50 5.24 5.24 5700.0 1
Cytochrome P450 3A4
CHEMBL340
IC50 5.2 5.16 6300.0 2
Unchecked
CHEMBL612545
IC50 5.06 5.0 8800.0 2
Glycogen synthase kinase-3 beta
CHEMBL262
IC50 4.64 4.64 23000.0 1

Pharmacokinetic Data

Parameter Value Units Species
CL 8.0 mL.min-1.kg-1 Rattus norvegicus
CL 76.0 mL.min-1.kg-1 Mus musculus
CL 39.0 mL.min-1.kg-1 Rattus norvegicus
CL 21.0 mL.min-1.kg-1 Canis lupus familiaris
CL 34.0 mL.min-1.kg-1 Macaca fascicularis
CL 11.0 mL.min-1.kg-1 Homo sapiens
CL 54.0 mL.min-1.kg-1 Mus musculus
CL 37.0 mL.min-1.kg-1 Rattus norvegicus
CL 21.0 mL.min-1.kg-1 Canis lupus familiaris
CL 24.0 mL.min-1.kg-1 Macaca fascicularis
CL 10.0 mL.min-1.kg-1 Homo sapiens
CL 135.0 mL.min-1.kg-1 Mus musculus
CL 34.0 mL.min-1.kg-1 Macaca fascicularis
F 33.0 % Rattus norvegicus
F 34.0 % Mus musculus
F 11.0 % Mus musculus
F 35.0 % Macaca fascicularis
F 28.0 % Rattus norvegicus
F 60.0 % Macaca fascicularis
T1/2 1.8 hr Rattus norvegicus
T1/2 0.9 hr Mus musculus
T1/2 1.8 hr Macaca fascicularis

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Serine/threonine-protein kinase pim-3 Ki = 0.02 nM 10.7 Inhibition of recombinant human PIM3 using FAM-pimtide as substrate after 90 min... 30715878
Serine/threonine-protein kinase pim-1 Ki = 0.03 nM 10.52 Inhibition of recombinant human PIM1 using FAM-pimtide as substrate after 90 min... 30715878
Serine/threonine-protein kinase pim-1 Ki = 0.04 nM 10.4 Pim Kinase Binding Activity: PIM-1, -2, and -3 enzymes were generated as fusion ... -
Serine/threonine-protein kinase pim-2 Ki = 0.1 nM 10.0 Inhibition of recombinant human PIM2 using FAM-pimtide as substrate after 90 min... 30715878
MM1.S IC50 = 30.0 nM 7.52 Antiproliferative activity against human MM1S cells after 72 hrs in presence of ... 30715878
MM1.S IC50 = 70.0 nM 7.16 Antiproliferative activity against human MM1S cells after 72 hrs by CellTiter-Gl... 30715878
Dopamine receptor IC50 = 500.0 nM 6.3 Inhibition of dopamine receptor (unknown origin) 30715878
Cytochrome P450 3A4 Ki = 1120.0 nM 5.95 Time dependent inhibition of CYP3A4 (unknown origin) using testosterone as subst... 30715878
5-hydroxytryptamine receptor 1A IC50 = 2500.0 nM 5.6 Agonist activity at 5HT1A receptor (unknown origin) 30715878
Alpha-1A adrenergic receptor IC50 = 2500.0 nM 5.6 Antagonist activity at alpha 1a adrenergic receptor (unknown origin) 30715878
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 2700.0 nM 5.57 Inhibition of human ERG expressed in HEK293 cells after 5 mins by patch clamp as... 30715878
5-hydroxytryptamine receptor 1A IC50 = 4900.0 nM 5.31 Antagonist activity at 5HT1A receptor (unknown origin) 30715878
Mitogen-activated protein kinase kinase kinase kinase 4 IC50 = 5700.0 nM 5.24 Inhibition of MAP4K4 (unknown origin) by cell based assay 30715878
Cytochrome P450 3A4 IC50 = 6300.0 nM 5.2 Reversible inhibition of CYP3A4 (unknown origin) using testosterone as substrate 30715878
Cytochrome P450 3A4 IC50 = 7500.0 nM 5.12 Reversible inhibition of CYP3A4 (unknown origin) using midazolam as substrate 30715878
Unchecked IC50 = 8800.0 nM 5.06 Inhibition of sodium channel (unknown origin) at phasic phase by patch clamp ass... 30715878
Unchecked IC50 = 11500.0 nM 4.94 Inhibition of sodium channel (unknown origin) at tonic phase by patch clamp assa... 30715878
Glycogen synthase kinase-3 beta IC50 = 23000.0 nM 4.64 Inhibition of GSK3beta in human human MM1S cells 30715878

Literature References

PubMed DOI Target Context # Activities
- 10.6019/CHEMBL5303300 U2OS 304
- 10.6019/CHEMBL5303300 Fibroblast 304
- 10.6019/CHEMBL5303300 HEK-293T 304
30715878 10.1021/acs.jmedchem.8b01857 ADMET 33
30715878 10.1021/acs.jmedchem.8b01857 Unchecked 11
30715878 10.1021/acs.jmedchem.8b01857 MM1.S 6
30715878 10.1021/acs.jmedchem.8b01857 Cytochrome P450 3A4 5
30715878 10.1021/acs.jmedchem.8b01857 Serine/threonine-protein kinase PIM 4
- 10.6019/CHEMBL5303304 HEK-293T 3
30715878 10.1021/acs.jmedchem.8b01857 5-hydroxytryptamine receptor 1A 2
- 10.6019/CHEMBL5303304 U2OS 2
30715878 10.1021/acs.jmedchem.8b01857 Mus musculus 2
30715878 10.1021/acs.jmedchem.8b01857 Voltage-gated inwardly rectifying potassium channel KCNH2 1
30715878 10.1021/acs.jmedchem.8b01857 RPMI-8226 1
30715878 10.1021/acs.jmedchem.8b01857 Serine/threonine-protein kinase pim-1 1
- 10.6019/CHEMBL5308504 Bromodomain-containing protein 4 1
30715878 10.1021/acs.jmedchem.8b01857 Dopamine receptor 1
30715878 10.1021/acs.jmedchem.8b01857 Alpha-1A adrenergic receptor 1
30715878 10.1021/acs.jmedchem.8b01857 No relevant target 1
30715878 10.1021/acs.jmedchem.8b01857 Serine/threonine-protein kinase pim-3 1

Data from ChEMBL 36 via Core Engine