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Compound Detail

CHEMBL1946170

REGORAFENIB
💊 Approved Drug
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💊 Approved Drug
CNC(=O)c1cc(Oc2ccc(NC(=O)Nc3ccc(Cl)c(C(F)(F)F)c3)c(F)c2)ccn1

Basic Information

ChEMBL ID CHEMBL1946170
Name REGORAFENIB
Phase Approved
Structure Type MOL
InChI Key FNHKPVJBJVTLMP-UHFFFAOYSA-N
Therapeutic ✓ Yes

Known Names

BAY 73-4506 BAY 73-4506 monohydrate BAY-73-4506 BAY-73-4506 MONOHYDRATE BAY-734506 BAY-734506 MONOHYDRATE Regorafenib Regorafenib anhydrous Regorafenib hydrate Regorafenib monohydrate Stivarga
54
Targets
137
Activities
4
Assay Types
8
PK Parameters
20
Publications
11
Known Names
20
Indications
10
Mechanisms

Molecular Properties

482.8
MW (Da)
5.69
ALogP
4
HBA
3
HBD
92.3
PSA (Ų)
0.41
QED
1
Ro5 Violations
5
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2012
Availability Prescription
Chirality Achiral

Routes of Administration

Oral

Flags

Black Box Warning
USAN Stem -rafenib
USAN Year 2011

Extended Properties

Molecular Formula C21H15ClF4N4O3
MW 482.82
Aromatic Rings 3
Heavy Atoms 33
NP-Likeness -1.82

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Tyrosine-protein kinase ABL inhibitor INHIBITOR Tyrosine-protein kinase ABL1
Serine/threonine-protein kinase RAF inhibitor INHIBITOR RAF proto-oncogene serine/threonine-protein kinase
Stem cell growth factor receptor inhibitor INHIBITOR Mast/stem cell growth factor receptor Kit
Fibroblast growth factor receptor 1 inhibitor INHIBITOR Fibroblast growth factor receptor 1
MAP kinase p38 beta inhibitor INHIBITOR Mitogen-activated protein kinase 11
Fibroblast growth factor receptor 2 inhibitor INHIBITOR Fibroblast growth factor receptor 2
Tyrosine-protein kinase FRK inhibitor INHIBITOR Tyrosine-protein kinase FRK
Discoidin domain-containing receptor 2 inhibitor INHIBITOR Discoidin domain-containing receptor 2
Serine/threonine-protein kinase B-raf inhibitor INHIBITOR Serine/threonine-protein kinase B-raf
Tyrosine-protein kinase TIE-2 inhibitor INHIBITOR Angiopoietin-1 receptor

Indications

Colorectal Neoplasms Colorectal Neoplasms Colorectal Neoplasms Colorectal Neoplasms Neoplasms Neoplasms Carcinoma, Hepatocellular Colonic Neoplasms Esophageal Neoplasms Gastrointestinal Stromal Tumors Bile Duct Neoplasms Biliary Tract Neoplasms Carcinoma, Adenoid Cystic Carcinoma, Renal Cell Cholangiocarcinoma Cholangiocarcinoma Digestive System Neoplasms Fallopian Tube Neoplasms Glioblastoma Hemangiosarcoma

ATC Classification

L01EX05
regorafenib
Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Level 2: ANTINEOPLASTIC AGENTS

Drug Warnings

Black Box Warning
hepatotoxicity
Country: United States

Activity Summary

IC50 111 meas. best 9.3
Kd 23 meas. best 8.15
EC50 2 meas. best 6.05
Ki 1 meas. best 8.38

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Bifunctional epoxide hydrolase 2
CHEMBL2409
IC50 9.3 9.3 0.5 1
Vascular endothelial growth factor receptor 2
CHEMBL3337
IC50 8.82 8.5267 1.5 3
Vascular endothelial growth factor receptor 3
CHEMBL4758
IC50 8.82 7.8333 1.5 3
Angiopoietin-1 receptor
CHEMBL4128
IC50 8.82 7.665 1.5 2
Serine/threonine-protein kinase B-raf
CHEMBL5145
IC50 8.82 7.7933 1.5 6
Fibroblast growth factor receptor 1
CHEMBL3650
IC50 8.82 7.76 1.5 2
Proto-oncogene tyrosine-protein kinase receptor Ret
CHEMBL2041
IC50 8.82 7.9447 1.5 19
RAF proto-oncogene serine/threonine-protein kinase
CHEMBL1906
IC50 8.82 8.655 1.5 4
Platelet-derived growth factor receptor beta
CHEMBL1913
IC50 8.82 8.24 1.5 2
Vascular endothelial growth factor receptor 1
CHEMBL1868
IC50 8.82 8.045 1.5 6
BaF3
CHEMBL614524
IC50 8.41 8.41 3.9 1
Vascular endothelial growth factor receptor 2
CHEMBL279
IC50 8.4 8.3675 4.0 8
Vascular endothelial growth factor receptor 2
CHEMBL279
Ki 8.38 8.38 4.2 1
HUVEC
CHEMBL613979
IC50 8.38 8.38 4.2 1
Mast/stem cell growth factor receptor Kit
CHEMBL1936
IC50 8.21 7.114 6.1 10
Ephrin type-A receptor 1
CHEMBL5810
Kd 8.15 8.15 7.0 1
Unchecked
CHEMBL612545
IC50 7.66 5.4179 22.0 14
Receptor-interacting serine/threonine-protein kinase 2
CHEMBL5014
IC50 7.39 7.39 41.0 1
Vascular endothelial growth factor receptor 3
CHEMBL1955
IC50 7.38 7.36 42.0 2
Receptor-type tyrosine-protein kinase FLT3
CHEMBL1974
IC50 7.09 7.09 82.0 1
Proto-oncogene tyrosine-protein kinase receptor Ret
CHEMBL2041
Kd 6.9 6.9 126.0 1
HCT-116
CHEMBL394
IC50 6.8 6.0433 160.0 3
Mitogen-activated protein kinase kinase kinase 20
CHEMBL3886
Kd 6.56 6.56 274.0 1
Epithelial discoidin domain-containing receptor 1
CHEMBL5319
Kd 6.45 6.45 358.0 1
Receptor-interacting serine/threonine-protein kinase 3
CHEMBL1795199
Kd 6.43 6.43 368.0 1
Discoidin domain-containing receptor 2
CHEMBL5122
Kd 6.38 6.38 421.0 1
Mitogen-activated protein kinase kinase kinase 1
CHEMBL3956
Kd 6.33 6.33 465.0 1
Receptor-type tyrosine-protein kinase FLT3
CHEMBL1974
Kd 6.25 6.25 562.0 1
LIM domain kinase 1
CHEMBL3836
Kd 6.21 6.21 616.0 1
MAP kinase-activated protein kinase 2
CHEMBL2208
Kd 6.17 6.17 682.0 1
Mitogen-activated protein kinase 14
CHEMBL260
Kd 6.15 6.15 705.0 1
Cyclin-dependent kinase 17
CHEMBL5790
Kd 6.14 6.14 719.0 1
Unchecked
CHEMBL612545
Kd 6.14 6.14 730.0 2
Breakpoint cluster region protein
CHEMBL5146
Kd 6.13 6.13 739.0 1
Tyrosine-protein kinase ABL1
CHEMBL1862
Kd 6.12 6.12 753.0 1
Receptor-interacting serine/threonine-protein kinase 2
CHEMBL5014
Kd 6.12 6.12 767.0 1
Platelet-derived growth factor receptor alpha
CHEMBL2007
IC50 6.09 6.09 810.0 1
Ephrin type-A receptor 2
CHEMBL2068
Kd 6.08 6.08 832.0 1
Influenza A virus
CHEMBL613740
EC50 6.05 6.05 890.0 1
Ephrin type-A receptor 5
CHEMBL3987
Kd 5.95 5.95 1123.0 1
SW-620
CHEMBL612262
IC50 5.93 5.93 1170.0 1
MDA-MB-231
CHEMBL400
IC50 5.92 5.92 1210.0 1
SARS-CoV-2
CHEMBL4303835
IC50 5.78 4.9933 1670.0 3
Glycine receptor subunit alpha-1
CHEMBL5845
EC50 5.75 5.75 1800.0 1
Mitogen-activated protein kinase 11
CHEMBL3961
Kd 5.72 5.72 1911.0 1
A549
CHEMBL392
IC50 5.69 5.69 2050.0 1
Dual specificity protein kinase CLK1
CHEMBL4224
Kd 5.68 5.68 2107.0 1
ADMET
CHEMBL612558
IC50 5.67 5.67 2160.0 1
HeLa
CHEMBL399
IC50 5.58 5.58 2660.0 1
MCF7
CHEMBL387
IC50 5.57 5.57 2710.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 50696.0 ng.hr.mL-1 Rattus norvegicus
CL 18.0 mL.min-1.g-1 Mus musculus
CL 59.18 ml/hr Rattus norvegicus
Cmax 6430.97 nM Rattus norvegicus
Ka 0.138 /hr Rattus norvegicus
MRT 7.29 hr Rattus norvegicus
T1/2 5.06 hr Rattus norvegicus
Tmax 8.07 hr Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Bifunctional epoxide hydrolase 2 IC50 = 0.5 nM 9.3 Inhibition of human recombinant soluble epoxide hydrolase assessed as cyano(6-me... 23726028
Serine/threonine-protein kinase B-raf IC50 = 1.5 nM 8.82 Inhibition of BRAF (unknown origin) 31284081
Angiopoietin-1 receptor IC50 = 1.5 nM 8.82 Inhibition of GST-tagged TIE2 (unknown origin) using biotin-Ahx-EPKDDAYPLYSDFG p... 31284081
Vascular endothelial growth factor receptor 3 IC50 = 1.5 nM 8.82 Inhibition of mouse VEGFR-3 (818 to 1363 residues) 31284081
Vascular endothelial growth factor receptor 2 IC50 = 1.5 nM 8.82 Inhibition of mouse VEGFR-2 (785 to 1376 residues) 31284081
Vascular endothelial growth factor receptor 1 IC50 = 1.5 nM 8.82 Inhibition of VEGFR1 (unknown origin) 31284081
Platelet-derived growth factor receptor beta IC50 = 1.5 nM 8.82 Inhibition of PDGFR beta (561 to 1106 residues) (unknown origin) 31284081
RAF proto-oncogene serine/threonine-protein kinase IC50 = 1.5 nM 8.82 Inhibition of RAF1 (unknown origin) 31284081
Fibroblast growth factor receptor 1 IC50 = 1.5 nM 8.82 Inhibition of FGFR1 (unknown origin) 31284081
Proto-oncogene tyrosine-protein kinase receptor Ret IC50 = 1.5 nM 8.82 Inhibition of RET (unknown origin) by HTRF assay 34402300
Proto-oncogene tyrosine-protein kinase receptor Ret IC50 = 1.5 nM 8.82 Inhibition of human RET kinase using IGF1Rtide as substrate incubated for 40 min... 35305461
Proto-oncogene tyrosine-protein kinase receptor Ret IC50 = 1.5 nM 8.82 Inhibition of RET (unknown origin) 37944387
Proto-oncogene tyrosine-protein kinase receptor Ret IC50 = 1.5 nM 8.82 Inhibition of recombinant RET (unknown origin) 37285684
RAF proto-oncogene serine/threonine-protein kinase IC50 = 2.5 nM 8.6 Inhibition of RAF1 (305 to 648 residues) (unknown origin) by HTRF assay 34402300
RAF proto-oncogene serine/threonine-protein kinase IC50 = 2.5 nM 8.6 Inhibition of human recombinant RAF-1 (305 to 648 residues) by HTRF assay 37944387
RAF proto-oncogene serine/threonine-protein kinase IC50 = 2.5 nM 8.6 Inhibition of recombinant Raf-1 (305 to 648 residues) (unknown origin) 37285684
BaF3 IC50 = 3.89 nM 8.41 Antiproliferative activity against VEGFR2-transformed mouse BaF3 cells assessed ... 37429211
Vascular endothelial growth factor receptor 2 IC50 = 4.0 nM 8.4 Inhibition of VEGFR 2 (unknown origin) 33539089
Vascular endothelial growth factor receptor 2 IC50 = 4.2 nM 8.38 Inhibition of VEGFR2 (unknown origin) 37857324
Vascular endothelial growth factor receptor 2 IC50 = 4.2 nM 8.38 Inhibition of mouse recombinant VEGFR2 (785 to 1367 residues) in presence of ATP... 37944387

Literature References

PubMed DOI Target Context # Activities
31721578 10.1021/acs.jmedchem.9b01229 Mast/stem cell growth factor receptor Kit 27
26254279 10.18632/oncotarget.4214 Unchecked 18
30204441 10.1021/acs.jmedchem.8b00938 Mast/stem cell growth factor receptor Kit 16
35434624 10.1039/d1md00306b Unchecked 9
31158755 10.1016/j.ejmech.2019.05.056 HCT-116 9
32731184 10.1016/j.ejmech.2020.112643 HT-29 9
35434624 10.1039/d1md00306b ADMET 8
- 10.6019/CHEMBL4495565 SARS-CoV-2 8
31364850 10.1021/acs.jmedchem.9b00855 RAF proto-oncogene serine/threonine-protein kinase 6
31364850 10.1021/acs.jmedchem.9b00855 Tyrosine-protein kinase ABL1 6
28991465 10.1021/acs.jmedchem.7b00841 Mast/stem cell growth factor receptor Kit 5
29191878 10.1126/science.aan4368 Unchecked 4
37468498 10.1038/s41467-023-40064-9 Bile acid receptor 4
30774864 10.1039/C8MD00463C UDP-glucuronosyltransferase 1A1 4
- 10.6019/CHEMBL4495565 ADMET 4
- 10.6019/CHEMBL4495565 Vero C1008 4
31364850 10.1021/acs.jmedchem.9b00855 Vascular endothelial growth factor receptor 2 3
31364850 10.1021/acs.jmedchem.9b00855 Vascular endothelial growth factor receptor 3 3
32731184 10.1016/j.ejmech.2020.112643 FHC 3
31364850 10.1021/acs.jmedchem.9b00855 Mitogen-activated protein kinase 14 3

Data from ChEMBL 36 via Core Engine