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Compound Detail

CHEMBL2105717

CABOZANTINIB
💊 Approved Drug
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💊 Approved Drug
COc1cc2nccc(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3)c2cc1OC

Basic Information

ChEMBL ID CHEMBL2105717
Name CABOZANTINIB
Phase Approved
Structure Type MOL
InChI Key ONIQOQHATWINJY-UHFFFAOYSA-N
Therapeutic ✓ Yes

Known Names

BMS-907351 FREE BASE Cabozantinib XL-184 FREE BASE
75
Targets
297
Activities
3
Assay Types
6
PK Parameters
20
Publications
3
Known Names
20
Indications

Molecular Properties

501.5
MW (Da)
5.54
ALogP
6
HBA
2
HBD
98.8
PSA (Ų)
0.31
QED
2
Ro5 Violations
8
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2012
Availability Prescription
Chirality Achiral

Routes of Administration

Oral

Flags

Black Box Warning First in Class
USAN Stem -tinib
USAN Year 2010

Extended Properties

Molecular Formula C28H24FN3O5
MW 501.51
Aromatic Rings 4
Heavy Atoms 37
NP-Likeness -0.76

Indications

Neoplasms Neoplasms Carcinoma, Hepatocellular Carcinoma, Medullary Carcinoma, Non-Small-Cell Lung Carcinoma, Renal Cell Carcinoma, Renal Cell Carcinoma, Renal Cell Carcinoma, Renal Cell Carcinoma, Renal Cell Carcinoma, Renal Cell Carcinoma, Renal Cell Thyroid Neoplasms Thyroid Neoplasms Thyroid Neoplasms Adenocarcinoma, Follicular Adrenal Cortex Neoplasms Astrocytoma Bile Duct Neoplasms Breast Neoplasms

ATC Classification

L01EX07
cabozantinib
Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Level 2: ANTINEOPLASTIC AGENTS

Activity Summary

IC50 276 meas. best 10.46
Kd 20 meas. best 7.28
Ki 1 meas. best 10.46

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Vascular endothelial growth factor receptor 2
CHEMBL279
Ki 10.46 10.46 0.0 1
Vascular endothelial growth factor receptor 2
CHEMBL279
IC50 10.46 8.5921 0.0 33
Receptor-type tyrosine-protein kinase FLT3
CHEMBL1974
IC50 9.22 7.6233 0.6 9
BaF3
CHEMBL614524
IC50 8.89 8.276 1.3 5
SAFB-like transcription modulator
CHEMBL4523469
IC50 8.89 8.89 1.3 1
Hepatocyte growth factor receptor
CHEMBL3717
IC50 8.89 7.8785 1.3 40
Unchecked
CHEMBL612545
IC50 8.85 6.9557 1.4 7
H-2 class II histocompatibility antigen gamma chain/Proto-oncogene tyrosine-protein kinase ROS
CHEMBL6066844
IC50 8.82 8.82 1.5 1
Proto-oncogene tyrosine-protein kinase receptor Ret
CHEMBL2041
IC50 8.62 7.483 2.4 47
MHCC97H
CHEMBL4296470
IC50 8.58 8.58 2.6 1
Aurora kinase B/Receptor-type tyrosine-protein kinase
CHEMBL3430908
IC50 8.54 8.54 2.9 1
Tyrosine-protein kinase receptor UFO
CHEMBL4895
IC50 8.47 7.9283 3.4 12
Mast/stem cell growth factor receptor Kit
CHEMBL1936
IC50 8.4 7.828 4.0 10
EBC-1
CHEMBL4296411
IC50 8.32 7.5525 4.8 4
Vascular endothelial growth factor receptor 3
CHEMBL1955
IC50 8.22 8.22 6.0 1
MKN-45
CHEMBL614354
IC50 8.16 6.5033 6.9 3
Hs746T
CHEMBL614579
IC50 8.0 8.0 9.9 1
Fibroblast growth factor receptor 1
CHEMBL3650
IC50 7.95 7.95 11.3 2
HepG2
CHEMBL395
IC50 7.92 5.63 12.0 5
SNU-5
CHEMBL614934
IC50 7.92 7.63 12.1 3
Vascular endothelial growth factor receptor 1
CHEMBL1868
IC50 7.92 7.92 12.0 2
Angiopoietin-1 receptor
CHEMBL4128
IC50 7.84 7.84 14.3 5
Epidermal growth factor receptor
CHEMBL203
IC50 7.72 6.6267 19.0 3
NON-PROTEIN TARGET
CHEMBL3879801
IC50 7.66 6.83 21.9 2
HEK293
CHEMBL614818
IC50 7.57 6.5433 27.0 3
Coiled-coil domain-containing protein 6/Tyrosine-protein kinase receptor RET
CHEMBL3430904
IC50 7.47 6.76 34.0 2
NCI-H460
CHEMBL396
IC50 7.4 6.03 40.1 3
HUVEC
CHEMBL613979
IC50 7.35 6.235 45.0 2
Receptor-type tyrosine-protein kinase FLT3
CHEMBL1974
Kd 7.28 7.28 53.0 1
Macrophage-stimulating protein receptor
CHEMBL2689
IC50 7.16 7.035 69.0 2
High affinity nerve growth factor receptor
CHEMBL2815
IC50 7.14 7.12 72.3 2
Proto-oncogene tyrosine-protein kinase receptor Ret
CHEMBL2041
Kd 7.07 7.07 86.0 1
NCI-H1993
CHEMBL1075527
IC50 6.96 6.96 110.0 1
Proto-oncogene tyrosine-protein kinase Src
CHEMBL267
IC50 6.75 6.75 178.0 1
Kinesin-1 heavy chain/ Tyrosine-protein kinase receptor RET
CHEMBL3430888
IC50 6.72 6.72 190.0 1
Epithelial discoidin domain-containing receptor 1
CHEMBL5319
Kd 6.68 6.68 209.0 1
HeLa
CHEMBL399
IC50 6.5 5.51 320.0 3
A549
CHEMBL392
IC50 6.48 5.4155 330.0 11
Breakpoint cluster region protein
CHEMBL5146
Kd 6.47 6.47 342.0 1
MCF7
CHEMBL387
IC50 6.35 5.3644 450.0 9
Discoidin domain-containing receptor 2
CHEMBL5122
Kd 6.3 6.3 501.0 1
Tyrosine-protein kinase FRK
CHEMBL4223
Kd 6.25 6.25 560.0 1
Ephrin type-A receptor 2
CHEMBL2068
Kd 6.13 6.13 746.0 1
Receptor-interacting serine/threonine-protein kinase 2
CHEMBL5014
Kd 6.12 6.12 767.0 1
Tyrosine-protein kinase ABL2
CHEMBL4014
Kd 6.04 6.04 918.0 1
Tyrosine-protein kinase Lck
CHEMBL258
Kd 5.98 5.98 1045.0 1
Tyrosine-protein kinase ABL1
CHEMBL1862
Kd 5.96 5.96 1098.0 1
Tyrosine-protein kinase HCK
CHEMBL3234
Kd 5.96 5.96 1098.0 1
Tyrosine-protein kinase Lyn
CHEMBL3905
Kd 5.88 5.88 1333.0 1
CAKI-1
CHEMBL614067
IC50 5.78 5.78 1660.0 1

Pharmacokinetic Data

Parameter Value Units Species
CL 3.16 uL.min-1.(10^6cells)-1 Rattus norvegicus
CL 6.76 uL.min-1.(10^6cells)-1 Homo sapiens
Cmax 1104.66 nM Homo sapiens
t1/2 - - Homo sapiens
T1/2 112.0 hr Homo sapiens
Tmax 4.0 hr Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Vascular endothelial growth factor receptor 2 IC50 = 0.035 nM 10.46 Inhibition of full length recombinant human GST or His-tagged VEGFR2 using poly ... 27068889
Vascular endothelial growth factor receptor 2 Ki = 0.035 nM 10.46 In-Vitro Kinase Inhibition Assay: Compounds 2-4 and cabozantinib were each teste... -
Vascular endothelial growth factor receptor 2 IC50 = 0.035 nM 10.46 Inhibition of VEGFR-2 (unknown origin) 37285684
Vascular endothelial growth factor receptor 2 IC50 = 0.035 nM 10.46 Inhibition of VEGFR2 (unknown origin) 37683364
Vascular endothelial growth factor receptor 2 IC50 = 0.035 nM 10.46 Inhibition of recombinant VEGFR2 (unknown origin) incubated for 120 mins by Perk... 34402300
Vascular endothelial growth factor receptor 2 IC50 = 0.035 nM 10.46 Inhibition of human recombinant full length VEGFR2 in presence of ATP by alphasc... 34402300
Vascular endothelial growth factor receptor 2 IC50 = 0.035 nM 10.46 Inhibition of recombinant human full length KDR using poly(Glu, Tyr) as substrat... 36358010
Vascular endothelial growth factor receptor 2 IC50 = 0.035 nM 10.46 Inhibition of VEGFR2 (unknown origin) 33429247
Vascular endothelial growth factor receptor 2 IC50 = 0.035 nM 10.46 Inhibition of VEGFR2 (unknown origin) 30248654
Vascular endothelial growth factor receptor 2 IC50 = 0.035 nM 10.46 Inhibition of human VEGFR-2 using poly(Glu, Tyr) as substrate by AlphaScreen ass... 26717201
Vascular endothelial growth factor receptor 2 IC50 = 0.035 nM 10.46 Inhibition of VEGFR2 (unknown origin) 27299736
Vascular endothelial growth factor receptor 2 IC50 = 0.035 nM 10.46 Inhibition of VEGFR-2 (unknown origin) 28412159
Vascular endothelial growth factor receptor 2 IC50 = 0.035 nM 10.46 Inhibition of recombinant human full length VEGFR2 using poly (Glu, Tyr) as subs... 28755635
Vascular endothelial growth factor receptor 2 IC50 = 0.035 nM 10.46 Inhibition of VEGFR2 (unknown origin) 31306818
Vascular endothelial growth factor receptor 2 IC50 = 0.035 nM 10.46 Inhibition of VEGFR2 phosphorylation (unknown origin) 28651979
Vascular endothelial growth factor receptor 2 IC50 = 0.086 nM 10.07 Inhibition of VEGFR-2 (unknown origin) by HTRF method 28412159
Vascular endothelial growth factor receptor 2 IC50 = 0.48 nM 9.32 Inhibition of KDR (unknown origin) using poly (Glu,Tyr) 4:1 as substrate after 1... 29407963
Receptor-type tyrosine-protein kinase FLT3 IC50 = 0.6 nM 9.22 Inhibition of FLT3 (unknown origin) phosphorylation 33719439
Hepatocyte growth factor receptor IC50 = 1.3 nM 8.89 Inhibition of c-Met (unknown origin) 38477575
Hepatocyte growth factor receptor IC50 = 1.3 nM 8.89 Inhibition of MET (unknown origin) 37262349

Literature References

PubMed DOI Target Context # Activities
26652860 10.1021/acs.jmedchem.5b01522 Proto-oncogene tyrosine-protein kinase receptor Ret 22
29133048 10.1016/j.ejmech.2017.09.018 Proto-oncogene tyrosine-protein kinase receptor Ret 15
29133048 10.1016/j.ejmech.2017.09.018 Unchecked 10
26254279 10.18632/oncotarget.4214 Vascular endothelial growth factor receptor 2 9
31382120 10.1016/j.ejmech.2019.07.044 SiHa 9
37229832 10.1016/j.ejmech.2023.115499 A549 8
35227978 10.1016/j.ejmech.2022.114215 A549 8
26254279 10.18632/oncotarget.4214 Hepatocyte growth factor receptor 8
39026631 10.1039/d4md00280f Unchecked 7
30503936 10.1016/j.ejmech.2018.11.057 HT-29 7
31382120 10.1016/j.ejmech.2019.07.044 MDA-MB-231 6
31382120 10.1016/j.ejmech.2019.07.044 Vascular endothelial growth factor receptor 2 6
- 10.6019/CHEMBL4495565 SARS-CoV-2 6
31382120 10.1016/j.ejmech.2019.07.044 T47D 6
31382120 10.1016/j.ejmech.2019.07.044 HeLa 6
29191878 10.1126/science.aan4368 Unchecked 5
30940564 10.1016/j.bmc.2019.03.049 HT-29 5
33601310 10.1016/j.ejmech.2021.113273 A549 5
29133048 10.1016/j.ejmech.2017.09.018 BaF3 5
31307762 10.1016/j.bmc.2019.07.016 SW-620 5

Data from ChEMBL 36 via Core Engine