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Compound Detail

CHEMBL495727

AT-9283
🧪 Phase II
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🧪 Phase II
O=C(Nc1c[nH]nc1-c1nc2ccc(CN3CCOCC3)cc2[nH]1)NC1CC1

Basic Information

ChEMBL ID CHEMBL495727
Name AT-9283
Phase Phase II
Structure Type MOL
InChI Key LOLPPWBBNUVNQZ-UHFFFAOYSA-N

Known Names

At 9283 At-9283 AT9283
144
Targets
219
Activities
2
Assay Types
14
PK Parameters
20
Publications
3
Known Names
4
Indications
6
Mechanisms

Molecular Properties

381.4
MW (Da)
2.07
ALogP
5
HBA
4
HBD
111.0
PSA (Ų)
0.54
QED
0
Ro5 Violations
5
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Achiral

Flags

Natural Product

Extended Properties

Molecular Formula C19H23N7O2
MW 381.44
Aromatic Rings 3
Heavy Atoms 28
NP-Likeness -2.10

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Tyrosine-protein kinase ABL inhibitor INHIBITOR Tyrosine-protein kinase ABL1
Serine/threonine-protein kinase Aurora-A inhibitor INHIBITOR Aurora kinase A
Serine/threonine-protein kinase Aurora-B inhibitor INHIBITOR Aurora kinase B
Tyrosine-protein kinase receptor FLT3 inhibitor INHIBITOR Receptor-type tyrosine-protein kinase FLT3
Tyrosine-protein kinase JAK2 inhibitor INHIBITOR Tyrosine-protein kinase JAK2
Tyrosine-protein kinase JAK3 inhibitor INHIBITOR Tyrosine-protein kinase JAK3

Indications

Multiple Myeloma Leukemia Lymphoma, Non-Hodgkin Neoplasms

Activity Summary

Kd 122 meas. best 8.52
IC50 97 meas. best 9.0

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Vascular endothelial growth factor receptor 3
CHEMBL1955
IC50 9.0 9.0 1.0 1
Proto-oncogene tyrosine-protein kinase receptor Ret
CHEMBL2041
IC50 9.0 9.0 1.0 1
Tyrosine-protein kinase Yes
CHEMBL2073
IC50 9.0 9.0 1.0 1
Tyrosine-protein kinase JAK3
CHEMBL2148
IC50 9.0 8.79 1.0 7
Ribosomal protein S6 kinase alpha-3
CHEMBL2345
IC50 9.0 9.0 1.0 1
Glycogen synthase kinase-3 beta
CHEMBL262
IC50 9.0 9.0 1.0 1
Tyrosine-protein kinase JAK2
CHEMBL2971
IC50 9.0 8.167 1.0 10
Non-receptor tyrosine-protein kinase TYK2
CHEMBL3553
IC50 9.0 7.885 1.0 4
Ribosomal protein S6 kinase alpha-2
CHEMBL3906
IC50 9.0 9.0 1.0 1
Fibroblast growth factor receptor 2
CHEMBL4142
IC50 9.0 8.5 1.0 2
Tyrosine-protein kinase Mer
CHEMBL5331
IC50 9.0 9.0 1.0 1
Aurora kinase B
CHEMBL2185
IC50 8.57 7.868 2.7 5
cAMP-dependent protein kinase catalytic subunit gamma
CHEMBL2743
Kd 8.52 8.52 3.0 1
Aurora kinase A
CHEMBL4722
IC50 8.52 8.1933 3.0 3
Tyrosine-protein kinase JAK2
CHEMBL2971
Kd 8.48 8.22 3.3 2
Tyrosine-protein kinase ABL1
CHEMBL1862
IC50 8.4 8.3 4.0 4
Glycogen synthase kinase-3 alpha
CHEMBL2850
Kd 8.22 8.22 6.0 1
Tyrosine-protein kinase JAK3
CHEMBL2148
Kd 8.18 8.18 6.6 1
Glycogen synthase kinase-3 beta
CHEMBL262
Kd 8.15 8.15 7.0 1
Hepatocyte growth factor receptor
CHEMBL3717
Kd 8.15 8.15 7.0 1
HT-29
CHEMBL384
IC50 8.15 7.285 7.0 2
MCF7
CHEMBL387
IC50 8.15 8.15 7.0 1
A549
CHEMBL392
IC50 8.15 7.22 7.0 2
HCT-116
CHEMBL394
IC50 8.15 7.7067 7.0 3
SW-620
CHEMBL612262
IC50 8.15 8.15 7.0 1
A2780
CHEMBL614004
IC50 8.15 8.15 7.0 1
MIA PaCa-2
CHEMBL614725
IC50 8.15 8.15 7.0 1
Ephrin type-A receptor 7
CHEMBL4602
Kd 8.1 8.1 8.0 1
Cyclin-dependent kinase 10
CHEMBL1795191
Kd 8.05 8.05 9.0 1
Vascular endothelial growth factor receptor 1
CHEMBL1868
IC50 8.0 8.0 10.0 1
Receptor-type tyrosine-protein kinase FLT3
CHEMBL1974
IC50 8.0 8.0 10.0 2
Platelet-derived growth factor receptor alpha
CHEMBL2007
IC50 8.0 8.0 10.0 1
Proto-oncogene tyrosine-protein kinase Src
CHEMBL267
IC50 8.0 8.0 10.0 1
Fibroblast growth factor receptor 3
CHEMBL2742
IC50 8.0 8.0 10.0 1
Vascular endothelial growth factor receptor 2
CHEMBL279
IC50 8.0 8.0 10.0 1
Ribosomal protein S6 kinase alpha-4
CHEMBL3125
IC50 8.0 8.0 10.0 1
Fibroblast growth factor receptor 1
CHEMBL3650
IC50 8.0 8.0 10.0 2
Serine/threonine-protein kinase D1
CHEMBL3863
IC50 8.0 8.0 10.0 1
Serine/threonine-protein kinase 17A
CHEMBL4525
IC50 8.0 8.0 10.0 1
[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial
CHEMBL4766
IC50 8.0 8.0 10.0 1
Proto-oncogene tyrosine-protein kinase receptor Ret
CHEMBL2041
Kd 7.96 7.96 11.0 1
BaF3
CHEMBL614524
IC50 7.96 7.8833 11.0 3
Non-receptor tyrosine-protein kinase TYK2
CHEMBL3553
Kd 7.92 7.235 12.0 2
Ephrin type-B receptor 6
CHEMBL5836
Kd 7.92 7.92 12.0 1
Activin receptor type-1-like
CHEMBL5311
Kd 7.82 7.82 15.0 1
SET-2
CHEMBL4523566
IC50 7.8 7.8 16.0 1
Aurora kinase A
CHEMBL4722
Kd 7.8 7.565 16.0 2
Ribosomal protein S6 kinase alpha-6
CHEMBL4924
Kd 7.8 7.8 16.0 1
TF-1
CHEMBL612552
IC50 7.8 7.8 16.0 1
HEL
CHEMBL613888
IC50 7.8 6.22 16.0 7

Pharmacokinetic Data

Parameter Value Units Species
AUC 1.9 uM.hr Mus musculus
AUC 0.91 uM.hr Mus musculus
AUC 7.7 uM.hr Mus musculus
CL 8.32 mL.min-1.g-1 Homo sapiens
CL 3.0 uL.min-1.(10^6cells)-1 Rattus norvegicus
Cmax 4900.0 nM Mus musculus
Cmax 450.0 nM Mus musculus
Cmax 8400.0 nM Mus musculus
F 24.0 % Mus musculus
F 100.0 % Mus musculus
F 24.0 % Mus musculus
T1/2 0.5 hr Mus musculus
T1/2 2.5 hr Mus musculus
T1/2 2.5 hr Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Glycogen synthase kinase-3 beta IC50 = 1.0 nM 9.0 Inhibition of GSK3-beta 19143567
Proto-oncogene tyrosine-protein kinase receptor Ret IC50 = 1.0 nM 9.0 Inhibition of Ret 19143567
Tyrosine-protein kinase JAK3 IC50 = 1.0 nM 9.0 Binding affinity to Jak3 19320489
Tyrosine-protein kinase JAK2 IC50 = 1.0 nM 9.0 Binding affinity to Jak2 19320489
Tyrosine-protein kinase Yes IC50 = 1.0 nM 9.0 Inhibition of Yes 19143567
Non-receptor tyrosine-protein kinase TYK2 IC50 = 1.0 nM 9.0 Inhibition of Tyk2 19143567
Ribosomal protein S6 kinase alpha-3 IC50 = 1.0 nM 9.0 Inhibition of Rsk2 19143567
Tyrosine-protein kinase Mer IC50 = 1.0 nM 9.0 Inhibition of Mer 19143567
Vascular endothelial growth factor receptor 3 IC50 = 1.0 nM 9.0 Inhibition of VEGFR3 19143567
Fibroblast growth factor receptor 2 IC50 = 1.0 nM 9.0 Inhibition of FGFR2 19143567
Ribosomal protein S6 kinase alpha-2 IC50 = 1.0 nM 9.0 Inhibition of Rsk3 19143567
Tyrosine-protein kinase JAK3 IC50 = 1.1 nM 8.96 Inhibition of JAK3 (unknown origin) 35749986
Tyrosine-protein kinase JAK3 IC50 = 1.1 nM 8.96 Inhibition of JAK3 (unknown origin) 32120325
Tyrosine-protein kinase JAK3 IC50 = 1.1 nM 8.96 Inhibition of JAK3 19143567
Tyrosine-protein kinase JAK3 IC50 = 1.1 nM 8.96 Inhibition of JAK 3 (unknown origin) 33539089
Tyrosine-protein kinase JAK2 IC50 = 1.2 nM 8.92 Inhibition of JAK2 (unknown origin) 32120325
Tyrosine-protein kinase JAK2 IC50 = 1.2 nM 8.92 Inhibition of JAK2 (unknown origin) 35749986
Tyrosine-protein kinase JAK2 IC50 = 1.2 nM 8.92 Inhibition of JAK2 19143567
Tyrosine-protein kinase JAK2 IC50 = 1.2 nM 8.92 Inhibition of JAK 2 (unknown origin) 33539089
Tyrosine-protein kinase JAK3 IC50 = 1.2 nM 8.92 Inhibition of JAK3 (unknown origin) incubated for 40 mins in presence of ATP by ... 33109396

Literature References

PubMed DOI Target Context # Activities
- 10.6019/CHEMBL5724801 Fibroblast 320
- 10.6019/CHEMBL5724801 U2OS 320
- 10.6019/CHEMBL5724801 HEK-293T 320
19143567 10.1021/jm800984v Mus musculus 13
36805946 10.1016/j.ejmech.2023.115198 HEL 9
- 10.6019/CHEMBL5303304 U2OS 8
- 10.6019/CHEMBL5303304 HEK-293T 8
29191878 10.1126/science.aan4368 Unchecked 5
33109396 10.1016/j.ejmech.2020.112934 HCT-116 5
33109396 10.1016/j.ejmech.2020.112934 K562 5
38843875 10.1021/acs.jmedchem.4c00197 Unchecked 5
33691794 10.1186/s13148-021-01037-1 A549 4
- 10.6019/CHEMBL4495565 SARS-CoV-2 4
- 10.6019/CHEMBL5303304 Fibroblast 4
38843875 10.1021/acs.jmedchem.4c00197 Non-receptor tyrosine-protein kinase TYK2 3
- 10.6019/CHEMBL3885741 Aurora kinase A 3
19143567 10.1021/jm800984v No relevant target 3
38843875 10.1021/acs.jmedchem.4c00197 Tyrosine-protein kinase JAK1 3
38843875 10.1021/acs.jmedchem.4c00197 Tyrosine-protein kinase JAK2 3
- 10.6019/CHEMBL3301361 ADMET 3

Data from ChEMBL 36 via Core Engine