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Compound Detail

CHEMBL4519023

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COc1cc2nc(C)nc(N[C@H](C)c3cc(N)cc(C(F)(F)F)c3)c2cc1O[C@H]1CCOC1

Basic Information

ChEMBL ID CHEMBL4519023
Phase Preclinical
Structure Type MOL
InChI Key XVFDNRYZXDHTHT-PXAZEXFGSA-N
21
Targets
61
Activities
2
Assay Types
16
PK Parameters
20
Publications
0
Known Names

Molecular Properties

462.5
MW (Da)
4.89
ALogP
7
HBA
2
HBD
91.5
PSA (Ų)
0.50
QED
0
Ro5 Violations
6
Rot. Bonds

Drug Information

Molecule Type Unknown
Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug Chemical Probe

Extended Properties

Molecular Formula C23H25F3N4O3
MW 462.47
Aromatic Rings 3
Heavy Atoms 33
NP-Likeness -0.77

Activity Summary

IC50 57 meas. best 8.52
Kd 4 meas. best 8.52

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Son of sevenless homolog 1
CHEMBL2079846
IC50 8.52 7.7513 3.0 8
Son of sevenless homolog 1
CHEMBL2079846
Kd 8.52 7.7175 3.0 4
SOS1-KRAS
CHEMBL5465393
IC50 8.4 8.194 4.0 10
Unchecked
CHEMBL612545
IC50 8.3 6.58 5.0 7
NCI-H358
CHEMBL614135
IC50 7.78 7.522 16.5 5
PANC-1
CHEMBL614139
IC50 7.75 7.75 17.8 1
MIA PaCa-2
CHEMBL614725
IC50 7.61 7.5567 24.8 3
SW-620
CHEMBL612262
IC50 7.52 7.41 30.1 2
K562
CHEMBL385
IC50 7.43 6.64 37.0 2
ASPC1
CHEMBL612588
IC50 7.19 7.19 64.4 1
NCI-H441
CHEMBL1075542
IC50 7.17 7.17 68.0 1
DLD-1
CHEMBL614285
IC50 6.99 6.88 102.0 2
A549
CHEMBL392
IC50 6.97 6.775 106.0 2
LoVo
CHEMBL614721
IC50 6.85 6.85 142.0 1
PC-3
CHEMBL390
IC50 5.86 5.46 1370.0 2
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
IC50 5.85 5.85 1400.0 1
Protein cereblon/SOS1
CHEMBL5291681
IC50 5.72 5.32 1900.0 3
Cytochrome P450 2C9
CHEMBL3397
IC50 4.92 4.92 12000.0 1
Cytochrome P450 2D6
CHEMBL289
IC50 4.85 4.85 14000.0 1
Cytochrome P450 2C8
CHEMBL3721
IC50 4.77 4.77 17000.0 1
Cytochrome P450 3A4
CHEMBL340
IC50 4.62 4.62 24000.0 1
Cytochrome P450 2C19
CHEMBL3622
IC50 4.39 4.39 41000.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 550.0 ng.hr.mL-1 Mus musculus
AUC 4680.0 ng.hr.mL-1 Mus musculus
CL 504.0 mL.min-1.kg-1 Mus musculus
CL 69.5 mL.min-1.kg-1 Rattus norvegicus
Cmax 521.11 nM Mus musculus
Cmax 2270.42 nM Mus musculus
F 100.0 % Mus musculus
F 100.0 % Rattus norvegicus
MRT 1.7 hr Mus musculus
MRT 2.98 hr Mus musculus
T1/2 1.3 hr Mus musculus
T1/2 0.18 hr Mus musculus
T1/2 4.48 hr Mus musculus
T1/2 0.6017 hr Rattus norvegicus
Tmax 0.5 hr Mus musculus
Tmax 0.9 hr Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Son of sevenless homolog 1 Kd = 3.0 nM 8.52 Binding affinity to SOS1 (unknown origin) assessed as dissociation constant by S... 33719426
Son of sevenless homolog 1 IC50 = 3.0 nM 8.52 Inhibition of SOS1 (unknown origin) by SPR assay 37542991
Son of sevenless homolog 1 IC50 = 4.0 nM 8.4 Inhibition of SOS1 (unknown origin) 37778239
SOS1-KRAS IC50 = 4.0 nM 8.4 Inhibition of human SOS1/GST-tagged KRAS G12C mutant (unknown origin) protein-pr... 37011767
SOS1-KRAS IC50 = 4.0 nM 8.4 Inhibition of SOS1/KRAS (unknown origin) protein-protein interaction by alpha sc... 37542991
SOS1-KRAS IC50 = 4.0 nM 8.4 Inhibition of SOS1/KRAS G12D mutant (unknown origin) protein-protein interaction... 33719426
SOS1-KRAS IC50 = 4.6 nM 8.34 Inhibition of SOS1/KRAS G12C mutant (unknown origin) protein-protein interaction... 38894918
SOS1-KRAS IC50 = 5.0 nM 8.3 Inhibition of N-terminal GST-tagged SOS1 (564 to 1049 residues)/N-terminal his6-... 38206836
Son of sevenless homolog 1 IC50 = 5.0 nM 8.3 Inhibition of GST-tagged SOS1 (564 to 1049 amino acids) (unknown origin) assesse... -
Unchecked IC50 = 5.0 nM 8.3 Inhibition of SOS1/KRAS (unknown origin) protein-protein interaction 34520956
SOS1-KRAS IC50 = 5.0 nM 8.3 Inhibition of SOS1/KRAS (unknown origin) protein-protein interaction by alpha sc... 38430853
SOS1-KRAS IC50 = 5.0 nM 8.3 Inhibition of SOS1/KRAS G12C mutant (unknown origin) protein-protein interaction 38665844
SOS1-KRAS IC50 = 8.3 nM 8.08 Inhibition of human recombinant SOS1 (residue 564-1049)/KRAS G12C mutant protein... 36384290
Son of sevenless homolog 1 Kd = 9.7 nM 8.01 Binding affinity to SOS1 (unknown origin) assessed as dissociation constant by S... 38206836
Son of sevenless homolog 1 Kd = 9.7 nM 8.01 Binding affinity to SOS1 (unknown origin) 38316747
SOS1-KRAS IC50 = 16.0 nM 7.8 Inhibition of human SOS1/GST-tagged KRAS G12C mutant (unknown origin) protein-pr... 37778239
NCI-H358 IC50 = 16.5 nM 7.78 Antiproliferative activity against human NCI-H358 cells harboring KRAS G12C muta... 36897932
Son of sevenless homolog 1 IC50 = 17.0 nM 7.77 Inhibition of SOS1 in human Calu-1 cells assessed as reduction in pERK level inc... 37778239
Unchecked IC50 = 17.0 nM 7.77 Antiproliferative activity against human GP2d cells harboring G12D mutant assess... 38206836
PANC-1 IC50 = 17.8 nM 7.75 Antiproliferative activity against human PANC-1 cells harboring KRAS G12D mutant... 36897932

Literature References

Data from ChEMBL 36 via Core Engine