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Compound Detail

CHEMBL3125890

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N#Cc1c(Oc2ccc(F)c(NC(=O)Cc3cccc(C(F)(F)F)c3)c2)ccc2nc(NC(=O)C3CC3)sc12

Basic Information

ChEMBL ID CHEMBL3125890
Phase Preclinical
Structure Type MOL
InChI Key OJFKUJDRGJSAQB-UHFFFAOYSA-N
28
Targets
63
Activities
3
Assay Types
15
PK Parameters
20
Publications
0
Known Names

Molecular Properties

554.5
MW (Da)
6.65
ALogP
6
HBA
2
HBD
104.1
PSA (Ų)
0.25
QED
2
Ro5 Violations
7
Rot. Bonds

Drug Information

Molecule Type Small molecule
Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula C27H18F4N4O3S
MW 554.53
Aromatic Rings 4
Heavy Atoms 39
NP-Likeness -2.14

Activity Summary

IC50 49 meas. best 8.85
Kd 9 meas. best 6.98
EC50 5 meas. best 5.84

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
RAF proto-oncogene serine/threonine-protein kinase
CHEMBL1906
IC50 8.85 8.254 1.4 5
Serine/threonine-protein kinase B-raf
CHEMBL5145
IC50 8.7 8.0594 2.0 17
CHL-1
CHEMBL1075422
IC50 8.68 8.68 2.1 1
NON-PROTEIN TARGET
CHEMBL3879801
IC50 7.6 7.02 25.0 2
HT-29
CHEMBL384
IC50 7.48 7.48 33.0 1
Unchecked
CHEMBL612545
IC50 7.31 7.305 49.0 2
Malme-3M
CHEMBL614021
IC50 7.3 7.3 50.0 1
SK-MEL-2
CHEMBL614917
IC50 7.22 7.22 60.0 1
Aurora kinase B
CHEMBL2185
IC50 7.18 7.18 66.0 1
Receptor-interacting serine/threonine-protein kinase 3
CHEMBL1795199
IC50 7.05 7.05 90.0 1
Receptor-interacting serine/threonine-protein kinase 3
CHEMBL1795199
Kd 6.98 6.8575 105.0 4
Receptor-interacting serine/threonine-protein kinase 1
CHEMBL5464
Kd 6.98 6.452 105.0 5
HT-144
CHEMBL2366291
IC50 6.96 6.96 110.0 1
Platelet-derived growth factor receptor beta
CHEMBL1913
IC50 6.92 6.92 120.0 1
Vascular endothelial growth factor receptor 2
CHEMBL279
IC50 6.8 6.8 160.0 1
A-375
CHEMBL613859
IC50 6.8 6.8 160.0 1
HMV-2 cell line
CHEMBL614826
IC50 6.7 6.7 200.0 1
Fibroblast growth factor receptor 3
CHEMBL2742
IC50 6.55 6.55 280.0 1
HMCB cell line
CHEMBL614824
IC50 6.46 6.46 350.0 1
Glycogen synthase kinase-3 beta
CHEMBL262
IC50 6.3 6.3 500.0 1
CDK2/Cyclin A2
CHEMBL3038469
IC50 6.24 6.24 580.0 1
Mitogen-activated protein kinase 14
CHEMBL260
IC50 6.22 6.22 600.0 1
Platelet-derived growth factor subunit A
CHEMBL3137294
IC50 6.21 6.21 610.0 1
Angiopoietin-1 receptor
CHEMBL4128
IC50 6.13 6.13 740.0 1
Cyclin-dependent kinase 1/cyclin B1
CHEMBL1907602
IC50 6.1 6.1 790.0 1
Serine/threonine-protein kinase Chk1
CHEMBL4630
IC50 5.85 5.85 1400.0 1
HT-29
CHEMBL384
EC50 5.84 5.84 1440.0 5
Inhibitor of nuclear factor kappa-B kinase subunit beta
CHEMBL1991
IC50 5.43 5.43 3700.0 1
Dual specificity mitogen-activated protein kinase kinase 1
CHEMBL3587
IC50 5.43 5.43 3700.0 1
A549
CHEMBL392
IC50 5.07 5.07 8500.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 15480.0 ng.hr.mL-1 Canis lupus familiaris
AUC 1429.0 ng.hr.mL-1 Canis lupus familiaris
AUC 32470.0 ng.hr.mL-1 Rattus norvegicus
AUC 2512.0 ng.hr.mL-1 Rattus norvegicus
AUC 2.482 ug.hr/kg Mus musculus
CL 11.73 mL.min-1.kg-1 Canis lupus familiaris
CL 6.667 mL.min-1.kg-1 Rattus norvegicus
F 108.0 % Canis lupus familiaris
F 51.7 % Rattus norvegicus
MRT 7.12 hr Canis lupus familiaris
MRT 2.23 hr Canis lupus familiaris
MRT 6.27 hr Rattus norvegicus
MRT 4.69 hr Rattus norvegicus
T1/2 2.15 hr Homo sapiens
T1/2 10.03 hr Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
RAF proto-oncogene serine/threonine-protein kinase IC50 = 1.4 nM 8.85 Inhibition of N-terminal FLAG-tagged wild type C-RAF (unknown origin) expressed ... 23906342
RAF proto-oncogene serine/threonine-protein kinase IC50 = 1.5 nM 8.82 Inhibition of CRAF (unknown origin) compound preincubated for 1 hr in presence o... 23906342
Serine/threonine-protein kinase B-raf IC50 = 2.0 nM 8.7 Inhibition of recombinant human GST-tagged BRAF V600E mutant expressed in baculo... 30613326
CHL-1 IC50 = 2.07 nM 8.68 Antiproliferative activity against human CHL-1 cells harbouring wild type B-Raf ... 32798788
Serine/threonine-protein kinase B-raf IC50 = 2.2 nM 8.66 Inhibition of BRAF V600E mutant (unknown origin) compound preincubated for 1 hr ... 23906342
Serine/threonine-protein kinase B-raf IC50 = 2.4 nM 8.62 Inhibition of N-terminal FLAG-tagged recombinant BRAF V600E mutant (unknown orig... 23906342
Serine/threonine-protein kinase B-raf IC50 = 2.4 nM 8.62 Inhibition of B-Raf V600E mutant (unknown origin) 32798788
Serine/threonine-protein kinase B-raf IC50 = 3.23 nM 8.49 Inhibition of N-terminal 6x-His-tagged BRAF kinase domain (unknown origin) expre... 29727562
Serine/threonine-protein kinase B-raf IC50 = 3.3 nM 8.48 Inhibition of BRAF V600E mutant (unknown origin) compound preincubated for 1 hr ... 23906342
Serine/threonine-protein kinase B-raf IC50 = 4.48 nM 8.35 Inhibition of N-terminal 6x-His-tagged BRAF V600E mutant (unknown origin) expres... 29727562
RAF proto-oncogene serine/threonine-protein kinase IC50 = 5.0 nM 8.3 Inhibition of CRAF (unknown origin) compound preincubated for 1 hr in presence o... 23906342
Serine/threonine-protein kinase B-raf IC50 = 8.0 nM 8.1 Inhibition of recombinant human full length GST-tagged BRAF expressed in baculov... 30613326
RAF proto-oncogene serine/threonine-protein kinase IC50 = 8.1 nM 8.09 Competitive inhibition of CRAF (unknown origin) in presence of 0.5 uM ATP by ELI... 23906342
Serine/threonine-protein kinase B-raf IC50 = 8.3 nM 8.08 Inhibition of N-terminal FLAG-tagged wild type BRAF (unknown origin) expressed i... 23906342
Serine/threonine-protein kinase B-raf IC50 = 8.3 nM 8.08 Inhibition of human full length wild type B-Raf 32798788
Serine/threonine-protein kinase B-raf IC50 = 12.0 nM 7.92 Inhibition of BRAF V600E mutant in human A375 cells assessed as phosphorylation ... 23906342
Serine/threonine-protein kinase B-raf IC50 = 15.0 nM 7.82 Competitive inhibition of BRAF V600E mutant (unknown origin) in presence of 5 uM... 23906342
Serine/threonine-protein kinase B-raf IC50 = 15.0 nM 7.82 Inhibition of recombinant human N-terminal GST-tagged B-Raf V600E mutant express... 27155899
Serine/threonine-protein kinase B-raf IC50 = 16.0 nM 7.8 Inhibition of BRAF V600E mutant in human A375 cells assessed as phosphorylation ... 23906342
NON-PROTEIN TARGET IC50 = 25.0 nM 7.6 Cytotoxicity against human COLO205 cells harboring B-Raf V600E mutant assessed a... 27155899

Literature References

PubMed DOI Target Context # Activities
23906342 10.1021/jm400778d Rattus norvegicus 14
29727562 10.1021/acs.jmedchem.8b00499 Serine/threonine-protein kinase B-raf 14
23906342 10.1021/jm400778d Serine/threonine-protein kinase B-raf 12
30763817 10.1016/j.ejmech.2019.01.066 IEC-6 9
30763817 10.1016/j.ejmech.2019.01.066 HeLa 9
23906342 10.1021/jm400778d RAF proto-oncogene serine/threonine-protein kinase 8
23906342 10.1021/jm400778d Canis familiaris 7
23906342 10.1021/jm400778d A-375 5
23906342 10.1021/jm400778d NON-PROTEIN TARGET 4
23906342 10.1021/jm400778d Unchecked 4
- 10.6019/CHEMBL4495565 SARS-CoV-2 4
31095385 10.1021/acs.jmedchem.9b00611 Mus musculus 4
26745854 10.1021/acs.jmedchem.5b01354 B-raf/RAF proto-oncogene serine/threonine-protein kinase 3
32798788 10.1016/j.ejmech.2020.112675 A-375 3
30763817 10.1016/j.ejmech.2019.01.066 Unchecked 2
31095385 10.1021/acs.jmedchem.9b00611 HT-29 2
28004573 10.1021/acs.jmedchem.6b01055 Heat shock factor protein 1 2
30613326 10.1021/acsmedchemlett.8b00364 Serine/threonine-protein kinase B-raf 2
26745854 10.1021/acs.jmedchem.5b01354 A549 2
23906342 10.1021/jm400778d No relevant target 2

Data from ChEMBL 36 via Core Engine