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Compound Detail

CHEMBL3348846

FEXAGRATINIB
🧪 Phase II
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🧪 Phase II
COc1cc(CCc2cc(NC(=O)c3ccc(N4C[C@@H](C)N[C@@H](C)C4)cc3)n[nH]2)cc(OC)c1

Basic Information

ChEMBL ID CHEMBL3348846
Name FEXAGRATINIB
Phase Phase II
Structure Type MOL
InChI Key VRQMAABPASPXMW-HDICACEKSA-N

Known Names

ABSK-091 ABSK091 Azd 4547 Azd-4547 Azd4547 Fexagratinib KB-74810
36
Targets
144
Activities
3
Assay Types
9
PK Parameters
20
Publications
7
Known Names
13
Indications
1
Mechanisms

Molecular Properties

463.6
MW (Da)
3.65
ALogP
6
HBA
3
HBD
91.5
PSA (Ų)
0.47
QED
0
Ro5 Violations
8
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Achiral

Flags

Natural Product Chemical Probe
USAN Stem -tinib

Extended Properties

Molecular Formula C26H33N5O3
MW 463.58
Aromatic Rings 3
Heavy Atoms 34
NP-Likeness -0.80

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Fibroblast growth factor receptor inhibitor INHIBITOR Fibroblast growth factor receptor

Indications

Adenocarcinoma Adenocarcinoma Breast Neoplasms Carcinoma, Non-Small-Cell Lung Carcinoma, Squamous Cell Carcinoma, Squamous Cell Multiple Myeloma Neoplasms Neoplasms Stomach Neoplasms Urinary Bladder Neoplasms Urinary Bladder Neoplasms Paraganglioma

Activity Summary

IC50 136 meas. best 9.7
EC50 4 meas. best 7.72
Kd 4 meas. best 9.7

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Fibroblast growth factor receptor 1
CHEMBL3650
IC50 9.7 8.9046 0.2 24
Fibroblast growth factor receptor 1
CHEMBL3650
Kd 9.7 9.7 0.2 1
Fibroblast growth factor receptor 2
CHEMBL4142
IC50 9.4 8.6244 0.4 16
Unchecked
CHEMBL612545
IC50 9.3 7.8371 0.5 7
NCI-H716
CHEMBL2366106
IC50 9.22 8.725 0.6 2
Fibroblast growth factor receptor 3
CHEMBL2742
IC50 9.22 8.4285 0.6 13
RT-112
CHEMBL614145
IC50 9.22 7.9133 0.6 3
SNU-16
CHEMBL613529
IC50 8.92 8.2533 1.2 9
Fibroblast growth factor receptor 3
CHEMBL2742
Kd 8.74 8.74 1.8 1
KG-1
CHEMBL612264
IC50 8.72 8.4675 1.9 4
Fibroblast growth factor receptor 2
CHEMBL4142
Kd 8.6 8.6 2.5 1
NCI-H1581
CHEMBL1075516
IC50 8.4 7.5829 4.0 7
NON-PROTEIN TARGET
CHEMBL3879801
IC50 8.19 7.45 6.4 5
Receptor-interacting serine/threonine-protein kinase 1
CHEMBL5464
IC50 7.92 7.92 12.0 1
DMS-114
CHEMBL614642
IC50 7.85 7.85 14.0 1
HT-29
CHEMBL384
EC50 7.72 7.72 19.0 2
Vascular endothelial growth factor receptor 2
CHEMBL279
IC50 7.62 7.4583 24.0 6
U-937
CHEMBL612794
EC50 7.51 7.51 31.0 1
Fibroblast growth factor receptor 4
CHEMBL3973
IC50 7.34 6.8081 45.7 16
TOV21G
CHEMBL4630716
EC50 7.28 7.28 52.0 1
A549
CHEMBL392
IC50 7.21 7.21 62.0 1
OPM-2
CHEMBL2366353
IC50 7.08 7.08 83.6 2
BaF3
CHEMBL614524
IC50 6.65 6.46 222.0 3
Receptor-interacting serine/threonine-protein kinase 2
CHEMBL5014
IC50 6.59 6.59 259.2 1
Huh-7
CHEMBL614039
IC50 6.55 6.55 284.3 1
Fibroblast growth factor receptor 4
CHEMBL3839
IC50 6.46 6.375 348.0 2
Aurora kinase A
CHEMBL4722
Kd 6.42 6.42 381.1 1
SK-HEP1
CHEMBL614912
IC50 5.56 5.56 2780.0 1
SGC-7901
CHEMBL614909
IC50 5.55 5.55 2800.0 1
HepG2
CHEMBL395
IC50 5.5 5.5 3130.0 1
MGC-803
CHEMBL3706566
IC50 5.21 5.21 6200.0 1
MDA-MB-231
CHEMBL400
IC50 5.14 5.14 7190.0 1
BGC-823
CHEMBL614526
IC50 5.1 5.1 7900.0 1
KYSE-150 cell line
CHEMBL613998
IC50 5.05 5.05 8920.0 1
Receptor-interacting serine/threonine-protein kinase 3
CHEMBL1795199
IC50 5.0 5.0 10000.0 1
ADMET
CHEMBL612558
IC50 4.74 4.74 18210.0 1
MDA-MB-435
CHEMBL614697
IC50 4.67 4.67 21580.0 1
U-87 MG
CHEMBL614247
IC50 4.59 4.59 25410.0 1
HUVEC
CHEMBL613979
IC50 4.42 4.42 37950.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 2076.72 ng.hr.mL-1 Mus musculus
AUC 9127.04 ng.hr.mL-1 Mus musculus
CL 16.05 mL.min-1.kg-1 Mus musculus
Cmax 4061.87 nM Mus musculus
Cmax 2912.12 nM Mus musculus
F 74.66 % Mus musculus
T1/2 2.29 hr Mus musculus
T1/2 2.55 hr Mus musculus
Vd 3.175 L.kg-1 Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Fibroblast growth factor receptor 1 Kd = 0.2 nM 9.7 Binding affinity to FGFR1 (unknown origin) assessed as dissociation constant 36096343
Fibroblast growth factor receptor 1 IC50 = 0.2 nM 9.7 Inhibition of recombinant human FGFR1 in presence of ATP 27914362
Fibroblast growth factor receptor 1 IC50 = 0.2 nM 9.7 Inhibition of human FGFR1 27326339
Fibroblast growth factor receptor 1 IC50 = 0.2 nM 9.7 Inhibition of recombinant human FGFR1 in presence of ATP at Km concentration 33940465
Fibroblast growth factor receptor 1 IC50 = 0.2 nM 9.7 Inhibition of recombinant human FGFR1 in the presence of ATP at Km concentration 33199155
Fibroblast growth factor receptor 2 IC50 = 0.4 nM 9.4 Inhibition of human FGFR2 using poly (Glu, Tyr)4:1 as substrate measured after 6... 31335138
Fibroblast growth factor receptor 2 IC50 = 0.4 nM 9.4 Inhibition of human FGFR2 using poly (Glu,Tyr)4:1 as substrate incubated for 60 ... 27326339
Unchecked IC50 = 0.5 nM 9.3 Antiproliferative activity against mouse BaF3/TEL-FGFR1 cells measured after 72 ... 31335138
Fibroblast growth factor receptor 3 IC50 = 0.6 nM 9.22 Inhibition of FGFR3 in human RT112 cells assessed as suppression of cell prolife... 27117427
Fibroblast growth factor receptor 1 IC50 = 0.6 nM 9.22 Inhibition of recombinant human FGFR1 using poly (Glu, Tyr) 4:1 as substrate aft... 27348537
Fibroblast growth factor receptor 2 IC50 = 0.6 nM 9.22 Inhibition of recombinant FGFR2 (unknown origin) using poly (Glu,Tyr)4:1 as subs... 28687204
Fibroblast growth factor receptor 1 IC50 = 0.6 nM 9.22 Inhibition of human FGFR1 using poly (Glu, Tyr)4:1 as substrate measured after 6... 31335138
RT-112 IC50 = 0.6 nM 9.22 Antiproliferative activity against human RT112 cells after 72 hrs by CCK-8 assay 27326339
NCI-H716 IC50 = 0.6 nM 9.22 Antiproliferative activity against human NCI-H716 cells expressing FGFR2 assesse... 36802596
Fibroblast growth factor receptor 1 IC50 = 0.7 nM 9.15 Inhibition of recombinant human FGFR1 using poly (Glu,Tyr) 4:1 as substrate afte... 28714692
Fibroblast growth factor receptor 1 IC50 = 0.8 nM 9.1 Inhibition of FGFR1 (unknown origin) using Poly (Glu,Tyr) 4:1 as substrate incub... 36802596
Fibroblast growth factor receptor 1 IC50 = 0.8 nM 9.1 Inhibition of phosphorylated FGFR1 (407 to 822 residues) (unknown origin) using ... 30108871
Fibroblast growth factor receptor 1 IC50 = 0.8 nM 9.1 Inhibition of recombinant FGFR1 (unknown origin) using (Glu,Tyr)4:1 as substrate... 27117427
Fibroblast growth factor receptor 1 IC50 = 0.9 nM 9.05 Inhibition of recombinant FGFR1 (unknown origin) using poly (Glu, Tyr) 4:1 as su... 29775937
Fibroblast growth factor receptor 1 IC50 = 0.95 nM 9.02 Inhibition of FGFR1 (unknown origin) by ELISA 38643670

Literature References

PubMed DOI Target Context # Activities
38643670 10.1016/j.ejmech.2024.116415 MDA-MB-231 12
27326339 10.1021/acsmedchemlett.6b00066 ADMET 10
32930584 10.1021/acs.jmedchem.0c01019 Fibroblast growth factor receptor 4 5
30108871 10.1039/C7MD00213K Fibroblast growth factor receptor 4 4
- 10.6019/CHEMBL3885741 Aurora kinase A 3
27348537 10.1021/acs.jmedchem.6b00056 NON-PROTEIN TARGET 3
28714692 10.1021/acs.jmedchem.7b00076 Fibroblast growth factor receptor 2 3
31335138 10.1021/acs.jmedchem.9b00510 Unchecked 3
28714692 10.1021/acs.jmedchem.7b00076 Fibroblast growth factor receptor 1 3
27117427 10.1016/j.bmcl.2016.04.028 Fibroblast growth factor receptor 1 3
27117427 10.1016/j.bmcl.2016.04.028 Fibroblast growth factor receptor 2 3
36096343 10.1016/j.bmcl.2022.128982 Fibroblast growth factor receptor 3
27326339 10.1021/acsmedchemlett.6b00066 Fibroblast growth factor receptor 2 2
27326339 10.1021/acsmedchemlett.6b00066 Vascular endothelial growth factor receptor 2 2
27117427 10.1016/j.bmcl.2016.04.028 Fibroblast growth factor receptor 3 2
25736993 10.1016/j.bmcl.2015.02.010 ADMET 2
27348537 10.1021/acs.jmedchem.6b00056 NCI-H1581 2
31335138 10.1021/acs.jmedchem.9b00510 Fibroblast growth factor receptor 1 2
27326339 10.1021/acsmedchemlett.6b00066 NCI-H1581 2
27326339 10.1021/acsmedchemlett.6b00066 Fibroblast growth factor receptor 1 2

Data from ChEMBL 36 via Core Engine