Identification

Name
Regorafenib
Accession Number
DB08896
Type
Small Molecule
Groups
Approved
Description

Regorafenib is an orally-administered inhibitor of multiple kinases. It is used for the treatment of metastatic colorectal cancer and advanced gastrointestinal stromal tumours. FDA approved on September 27, 2012. Approved use of Regorafenib was expanded to treat Hepatocellular Carcinoma in April, 2017.

Structure
Thumb
Synonyms
  • Regorafenib
  • Régorafénib
  • Regorafenibum
External IDs
BAY 73-4506 / BAY-73-4506 / BAY-734506
Product Ingredients
IngredientUNIICASInChI Key
Regorafenib monohydrateMGN125FS9D1019206-88-2ZOPOQLDXFHBOIH-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
StivargaTablet, film coated40 mg/1OralBayer2012-09-27Not applicableUs
StivargaTablet40 mgOralBayer2013-04-02Not applicableCanada
StivargaTablet, film coated40 mgOralBayer Pharma Ag2013-08-26Not applicableEu
StivargaTablet, film coated40 mgOralBayer Pharma Ag2013-08-26Not applicableEu
Categories
UNII
24T2A1DOYB
CAS number
755037-03-7
Weight
Average: 482.815
Monoisotopic: 482.076880893
Chemical Formula
C21H15ClF4N4O3
InChI Key
FNHKPVJBJVTLMP-UHFFFAOYSA-N
InChI
InChI=1S/C21H15ClF4N4O3/c1-27-19(31)18-10-13(6-7-28-18)33-12-3-5-17(16(23)9-12)30-20(32)29-11-2-4-15(22)14(8-11)21(24,25)26/h2-10H,1H3,(H,27,31)(H2,29,30,32)
IUPAC Name
4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide
SMILES
CNC(=O)C1=CC(OC2=CC(F)=C(NC(=O)NC3=CC=C(Cl)C(=C3)C(F)(F)F)C=C2)=CC=N1

Pharmacology

Indication

Regorafenib is indicated for the treatment of patients with metastatic colorectal cancer (CRC) who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if KRAS wild type, an anti-EGFR therapy. Regorafenib is also indicated for the treatment of patients with locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST) who have been previously treated with imatinib mesylate and sunitinib malate.

Associated Conditions
Pharmacodynamics
Not Available
Mechanism of action

Regorafenib is a small molecule inhibitor of multiple membrane-bound and intracellular kinases involved in normal cellular functions and in pathologic processes such as oncogenesis, tumor angiogenesis, and maintenance of the tumor microenvironment. In in vitro biochemical or cellular assays, regorafenib or its major human active metabolites M-2 and M-5 inhibited the activity of RET, VEGFR1, VEGFR2, VEGFR3, KIT, PDGFR-alpha, PDGFR-beta, FGFR1, FGFR2, TIE2, DDR2, TrkA, Eph2A, RAF-1, BRAF, BRAFV600E , SAPK2, PTK5, and Abl at concentrations of regorafenib that have been achieved clinically. In in vivo models, regorafenib demonstrated anti-angiogenic activity in a rat tumor model, and inhibition of tumor growth as well as anti-metastatic activity in several mouse xenograft models including some for human colorectal carcinoma.

TargetActionsOrganism
AVascular endothelial growth factor receptor 1
inhibitor
Human
AVascular endothelial growth factor receptor 2
inhibitor
Human
AVascular endothelial growth factor receptor 3
inhibitor
Human
AMast/stem cell growth factor receptor Kit
inhibitor
Human
APlatelet-derived growth factor receptor alpha
inhibitor
Human
APlatelet-derived growth factor receptor beta
inhibitor
Human
AFibroblast growth factor receptor 1
inhibitor
Human
AFibroblast growth factor receptor 2
inhibitor
Human
AAngiopoietin-1 receptor
inhibitor
Human
ADiscoidin domain-containing receptor 2
inhibitor
Human
AHigh affinity nerve growth factor receptor
inhibitor
Human
AEphrin type-A receptor 2
inhibitor
Human
ARAF proto-oncogene serine/threonine-protein kinase
inhibitor
Human
ASerine/threonine-protein kinase B-raf
inhibitor
Human
AMitogen-activated protein kinase 11
inhibitor
Human
ATyrosine-protein kinase FRK
inhibitor
Human
ATyrosine-protein kinase ABL1
inhibitor
Human
AProto-oncogene tyrosine-protein kinase receptor Ret
inhibitor
Human
Absorption

Cmax = 2.5 μg/mL; Tmax = 4 hours; AUC = 70.4 μgh/mL; Cmax, steady-state = 3.9 μg/mL; AUC, steady-state = 58.3 μgh/mL; The mean relative bioavailability of tablets compared to an oral solution is 69% to 83%.

Volume of distribution

Regorafenib undergoes enterohepatic circulation with multiple plasma concentration peaks observed across the 24-hour dosing interval.

Protein binding

Regorafenib is highly bound (99.5%) to human plasma proteins.

Metabolism

Regorafenib is metabolized by CYP3A4 and UGT1A9. The main circulating metabolites of regorafenib measured at steady-state in human plasma are M-2 (N-oxide) and M-5 (N-oxide and N-desmethyl), both of them having similar in vitro pharmacological activity and steady-state concentrations as regorafenib. M-2 and M-5 are highly protein bound (99.8% and 99.95%, respectively). Regorafenib is an inhibitor of P-glycoprotein [Label], while its active metabolites M-2 (N-oxide) and M-5 (N-oxide and N-desmethyl) are substrates of P-glycoprotein [1].

Route of elimination

Approximately 71% of a radiolabeled dose was excreted in feces (47% as parent compound, 24% as metabolites) and 19% of the dose was excreted in urine (17% as glucuronides) within 12 days after administration of a radiolabeled oral solution at a dose of 120 mg.

Half life

Regorafenib, 160 mg oral dose = 28 hours (14 - 58 hours); M2 metabolite, 160 mg oral dose = 25 hours (14-32 hours); M5 metabolite, 160 mg oral dose = 51 hours (32-72 hours);

Clearance
Not Available
Toxicity

The most common adverse reactions (≥20%) are asthenia/fatigue, HFSR, diarrhea, decreased appetite/food intake, hypertension, mucositis, dysphonia, and infection, pain (not otherwise specified), decreased weight, gastrointestinal and abdominal pain, rash, fever, and nausea

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AcebutololRegorafenib may increase the bradycardic activities of Acebutolol.
AcetaminophenThe serum concentration of Regorafenib can be increased when it is combined with Acetaminophen.
Acetyl sulfisoxazoleThe metabolism of Regorafenib can be decreased when combined with Acetyl sulfisoxazole.
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Regorafenib.
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Regorafenib.
Acetylsalicylic acidThe serum concentration of Acetylsalicylic acid can be increased when it is combined with Regorafenib.
AfatinibThe serum concentration of Afatinib can be increased when it is combined with Regorafenib.
AlclometasoneThe metabolism of Alclometasone can be decreased when combined with Regorafenib.
AlfuzosinThe metabolism of Alfuzosin can be decreased when combined with Regorafenib.
AlprenololRegorafenib may increase the bradycardic activities of Alprenolol.
Food Interactions
  • When taken with a high-fat meal, AUC increased by 48% and decreased mean AUC of M2 and M5 metabolites by 20% and 51% respectively.

References

General References
  1. Hotta K, Ueyama J, Tatsumi Y, Tsukiyama I, Sugiura Y, Saito H, Matsuura K, Hasegawa T: Lack of Contribution of Multidrug Resistance-associated Protein and Organic Anion-transporting Polypeptide to Pharmacokinetics of Regorafenib, a Novel Multi-Kinase Inhibitor, in Rats. Anticancer Res. 2015 Sep;35(9):4681-9. [PubMed:26254357]
External Links
KEGG Drug
D10138
PubChem Compound
11167602
PubChem Substance
175427139
ChemSpider
9342697
BindingDB
50363397
ChEBI
68647
ChEMBL
CHEMBL1946170
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Regorafenib
ATC Codes
L01XE21 — Regorafenib
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
FDA label
Download (457 KB)
MSDS
Download (479 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentAdvanced Cancers1
1Active Not RecruitingTreatmentGastrointestinal Stromal Tumors1
1Active Not RecruitingTreatmentMetastatic Colorectal Cancers1
1Active Not RecruitingTreatmentNeoplasms1
1CompletedNot AvailableNeoplasms2
1CompletedScreeningDietary Fats / Pharmacokinetics1
1CompletedTreatmentColorectal Cancers1
1CompletedTreatmentNeoplasms5
1CompletedTreatmentNeoplasms, Colorectal1
1CompletedTreatmentOncology1
1CompletedTreatmentTumors1
1Not Yet RecruitingTreatmentLocally Advanced Solid Malignancies / Metastatic Solid Malignancies1
1RecruitingOtherPediatric Oncology1
1RecruitingTreatmentHepatocellular,Carcinoma1
1RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)1
1RecruitingTreatmentPretreated Metastatic Colorectal Cancer1
1RecruitingTreatmentRectal Carcinoma1
1RecruitingTreatmentTumors, Solid1
1TerminatedTreatmentKRAS and NRAS Wild-type Colorectal Cancer1
1TerminatedTreatmentNeoplasms1
1, 2Active Not RecruitingTreatmentAdvanced Gastrointestinal Cancers1
1, 2Not Yet RecruitingTreatmentStage III Colorectal Cancer AJCC v8 / Stage IIIA Colorectal Cancer AJCC v8 / Stage IIIB Colorectal Cancer AJCC v8 / Stage IIIC Colorectal Cancer AJCC v8 / Stage IV Colorectal Cancer AJCC v8 / Stage IVA Colorectal Cancer AJCC v8 / Stage IVB Colorectal Cancer AJCC v8 / Stage IVC Colorectal Cancer AJCC v81
1, 2RecruitingTreatmentAdvanced and Metastatic Solid Tumor1
1, 2RecruitingTreatmentColorectal Cancers2
1, 2RecruitingTreatmentDigestive Cancers1
1, 2RecruitingTreatmentMCRC / Metastatic Colorectal Cancers1
1, 2RecruitingTreatmentNeoplasms Metastasis / Neoplasms, Esophageal / Stomach Neoplasms1
2Active Not RecruitingSupportive CareMalignant Neoplasms of Independent (Primary) Multiple Sites / Metastatic Colorectal Cancers1
2Active Not RecruitingTreatmentAdenocarcinoma of the Colon / Adenocarcinoma of the Rectum / Neoplasms, Colorectal1
2Active Not RecruitingTreatmentAdvanced Chemorefractory Colorectal Adenocarcinoma1
2Active Not RecruitingTreatmentCancer of the Bile Duct1
2Active Not RecruitingTreatmentCarcinoma, Adenoid Cystic1
2Active Not RecruitingTreatmentColon Adenocarcinoma / Rectal Adenocarcinoma / Stage III Colorectal Cancer / Stage III Colorectal Cancer AJCC v7 / Stage IIIA Colorectal Cancer / Stage IIIA Colorectal Cancer AJCC v7 / Stage IIIB Colorectal Cancer / Stage IIIB Colorectal Cancer AJCC v7 / Stage IIIC Colorectal Cancer / Stage IIIC Colorectal Cancer AJCC v7 / Stage IV Colorectal Cancer / Stage IV Colorectal Cancer AJCC v7 / Stage IVA Colorectal Cancer / Stage IVA Colorectal Cancer AJCC v7 / Stage IVB Colorectal Cancer / Stage IVB Colorectal Cancer AJCC v71
2Active Not RecruitingTreatmentEsophageal Cancers / Malignant Neoplasm of Stomach1
2Active Not RecruitingTreatmentGastrointestinal Stromal Tumors1
2Active Not RecruitingTreatmentGlioblastoma Multiforme (GBM)1
2Active Not RecruitingTreatmentMetastatic Biliary Tract Carcinoma1
2Active Not RecruitingTreatmentMetastatic Colorectal Adenocarcinoma1
2Active Not RecruitingTreatmentMetastatic Colorectal Cancers4
2Active Not RecruitingTreatmentNeoplasms, Colorectal1
2Active Not RecruitingTreatmentPancreatic Adenocarcinoma Metastatic1
2Active Not RecruitingTreatmentRenal Cell Adenocarcinoma1
2Active Not RecruitingTreatmentSarcomas1
2CompletedTreatmentAdenocarcinomas of the Gastroesophageal Junction / Node Positive Esophogeal Cancer / Stage IIB Esophageal Adenocarcinoma / Stage IIIA Esophageal Adenocarcinoma / Stage IIIB Esophageal Adenocarcinoma / Stage IIIC Esophageal Adenocarcinoma1
2CompletedTreatmentGastrointestinal Stromal Tumors (GISTs)1
2CompletedTreatmentMalignant Neoplasm of Pancreas1
2CompletedTreatmentMetastatic Disease / Neoplasms, Colorectal1
2CompletedTreatmentNeoplasms, Colorectal3
2Enrolling by InvitationTreatmentBreastcancer / Cancer, Breast / Colorectal Cancer (CRC) / Colorectal Cancers / CRC (Colorectal Cancer) / Lung Cancer Non-Small Cell Cancer (NSCLC) / Lung Cancers / Malignant Neoplasm of Pancreas / NSCLC (Non-small Cell Lung Carcinoma)1
2RecruitingNot AvailableMetastatic Colorectal Cancers1
2RecruitingTreatmentALK Fusion Protein Expression / BRAF wt Allele / Invasive Skin Melanoma / Melanoma / MET Fusion Gene Positive / NRAS wt Allele / NTRK1 Fusion Positive / NTRK2 Fusion Positive / NTRK3 Fusion Positive / RET Fusion Positive / ROS1 Fusion Positive / Stage III Cutaneous Melanoma AJCC v7 / Stage IIIA Cutaneous Melanoma AJCC v7 / Stage IIIB Cutaneous Melanoma AJCC v7 / Stage IIIC Cutaneous Melanoma AJCC v7 / Stage IV Cutaneous Melanoma AJCC v6 and v71
2RecruitingTreatmentAdult Angiosarcoma / Recurrent Adult Soft Tissue Sarcoma / Stage III Adult Soft Tissue Sarcoma / Stage IV Adult Soft Tissue Sarcoma1
2RecruitingTreatmentAdvanced Colorectal Cancer1
2RecruitingTreatmentAdvanced Solid Tumors / Multiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL)1
2RecruitingTreatmentCancer of the Ovary / Malignant Neoplasm of Pancreas / Melanoma / Sarcomas1
2RecruitingTreatmentCancers / Neoplasia / Neoplasms / Tumors1
2RecruitingTreatmentChondroma / Chondrosarcomas / Ewing Sarcomas / Sarcoma, Osteogenic1
2RecruitingTreatmentColorectal Adenocarcinoma1
2RecruitingTreatmentColorectal Cancers2
2RecruitingTreatmentEwing/Ewing-like Sarcoma / Liposarcoma / Rhabdomyosarcomas / Sarcoma, Osteogenic1
2RecruitingTreatmentGastrinoma / Glucagonoma / Insulinoma / Metastatic Gastrointestinal Carcinoid Tumor / Pancreatic Polypeptide Tumor / Pulmonary Carcinoid Tumor / Recurrent Gastrointestinal Carcinoid Tumor / Recurrent Islet Cell Carcinoma / Somatostatinoma1
2RecruitingTreatmentGastrointestinal Carcinoma, Non-colon / Non-Small Cell Lung Carcinoma (NSCLC) / Transitional Cell Carcinoma / Upper Aerodigestive Tract Carcinoma1
2RecruitingTreatmentGastrointestinal Stromal Tumors1
2RecruitingTreatmentGastrointestinal Stromal Tumour (GIST)1
2RecruitingTreatmentGastrointestinal Stromal Tumours1
2RecruitingTreatmentKRAS Gene Mutation / Metastatic Malignant Neoplasm in the Brain / Recurrent Non-Small Cell Lung Carcinoma / Stage IV Non-Small Cell Lung Cancer AJCC v71
2RecruitingTreatmentMalignant Neoplasm of Stomach1
2RecruitingTreatmentMelanoma1
2RecruitingTreatmentMetastatic Colorectal Cancers2
2RecruitingTreatmentNeoplasms, Ovarian1
2RecruitingTreatmentOvarian Carcinoma1
2RecruitingTreatmentPreviously Treated Metastatic Colorectal Cancer1
2RecruitingTreatmentThyroid Cancers1
2RecruitingTreatmentUrothelial Cancer (Urinary Bladder, Ureters, or Renal Pelvis Cancer)1
2TerminatedBasic ScienceMalignant Neoplasm of Colon1
2TerminatedTreatmentCRC (Colorectal Cancer) / Metastatic Colorectal Cancers1
2TerminatedTreatmentCancer of the Ovary / Fallopian Tube Cancer / Primary Peritoneal Cancer1
2TerminatedTreatmentColorectal Cancers / Palliative Care / Palliative Medicine / Supportive Care1
2TerminatedTreatmentMacular Degeneration1
2TerminatedTreatmentMetastatic Disease / Neoplasms, Colorectal1
2TerminatedTreatmentUpper GI Cancer1
2Unknown StatusTreatmentCholangiocarcinomas1
2Unknown StatusTreatmentRectal Carcinoma1
2WithdrawnTreatmentRectal Adenocarcinoma / Stage IIA Rectal Cancer / Stage IIB Rectal Cancer / Stage IIC Rectal Cancer / Stage IIIA Rectal Cancer / Stage IIIB Rectal Cancer1
2, 3Unknown StatusTreatmentAsian Colorectal Cancer Patients1
3Active Not RecruitingTreatmentColorectal Cancers1
3Active Not RecruitingTreatmentGastrointestinal Stromal Tumors1
3Active Not RecruitingTreatmentHepatocellular,Carcinoma1
3Active Not RecruitingTreatmentStage III (IIIB or IIIC) Colon Cancer1
3CompletedTreatmentMetastatic Colorectal Cancers1
3CompletedTreatmentNeoplasms, Colorectal2
3No Longer AvailableNot AvailableGastrointestinal Stromal Tumors1
3Not Yet RecruitingTreatmentGastro-oesophageal Cancer1
3RecruitingTreatmentGIST1
3RecruitingTreatmentMetastatic Colorectal Cancers1
3TerminatedTreatmentNeoplasms, Colorectal1
3WithdrawnTreatmentMetastatic Colorectal Cancers1
4RecruitingTreatmentNeoplasms, Colorectal1
4TerminatedSupportive CarePhysician Education1
Not AvailableActive Not RecruitingDiagnosticColorectal Cancers1
Not AvailableActive Not RecruitingScreeningMetastatic Colorectal Cancers1
Not AvailableCompletedNot AvailableMetastatic Colorectal Cancers1
Not AvailableCompletedNot AvailableNeoplasms1
Not AvailableCompletedNot AvailableNeoplasms, Colorectal5
Not AvailableNo Longer AvailableNot AvailableGastrointestinal Stromal Tumors1
Not AvailableNo Longer AvailableNot AvailableNeoplasms, Colorectal1
Not AvailableNot Yet RecruitingNot AvailableHepatocellular,Carcinoma1
Not AvailableRecruitingNot AvailableGastrointestinal Stromal Tumors1
Not AvailableRecruitingNot AvailableNeoplasms, Colorectal1
Not AvailableRecruitingNot AvailableNeoplasms, Hepatic1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral40 mg
Tablet, film coatedOral40 mg
Tablet, film coatedOral40 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2315715No2010-06-222018-12-22Canada
CA2526636No2012-10-022024-05-19Canada
CA2549558No2010-08-312020-01-12Canada
US7351834No2000-01-122020-01-12Us
US8680124No2010-06-022030-06-02Us
US8637553No2011-02-162031-02-16Us
US9458107No2011-04-082031-04-08Us
US9957232No2012-07-092032-07-09Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityInsoluble FDA label
Predicted Properties
PropertyValueSource
Water Solubility0.00102 mg/mLALOGPS
logP4.53ALOGPS
logP4.49ChemAxon
logS-5.7ALOGPS
pKa (Strongest Acidic)10.52ChemAxon
pKa (Strongest Basic)2.02ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area92.35 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity114.73 m3·mol-1ChemAxon
Polarizability41.23 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9649
Blood Brain Barrier+0.851
Caco-2 permeable-0.5138
P-glycoprotein substrateNon-substrate0.5086
P-glycoprotein inhibitor INon-inhibitor0.7141
P-glycoprotein inhibitor IINon-inhibitor0.9359
Renal organic cation transporterNon-inhibitor0.8938
CYP450 2C9 substrateNon-substrate0.6569
CYP450 2D6 substrateNon-substrate0.8212
CYP450 3A4 substrateNon-substrate0.5341
CYP450 1A2 substrateInhibitor0.6168
CYP450 2C9 inhibitorNon-inhibitor0.6171
CYP450 2D6 inhibitorNon-inhibitor0.9145
CYP450 2C19 inhibitorInhibitor0.637
CYP450 3A4 inhibitorNon-inhibitor0.7339
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6629
Ames testNon AMES toxic0.8143
CarcinogenicityNon-carcinogens0.8684
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.7885 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9488
hERG inhibition (predictor II)Non-inhibitor0.6415
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-001i-0130900000-7cfbbe70d59d3990bb46

Taxonomy

Description
This compound belongs to the class of organic compounds known as diarylethers. These are organic compounds containing the dialkyl ether functional group, with the formula ROR', where R and R' are aryl groups.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Ethers
Direct Parent
Diarylethers
Alternative Parents
Trifluoromethylbenzenes / N-phenylureas / Pyridinecarboxamides / Phenoxy compounds / Phenol ethers / 2-heteroaryl carboxamides / Chlorobenzenes / Fluorobenzenes / Aryl chlorides / Aryl fluorides
show 12 more
Substituents
Diaryl ether / N-phenylurea / Trifluoromethylbenzene / Pyridinecarboxamide / Pyridine carboxylic acid or derivatives / 2-heteroaryl carboxamide / Phenoxy compound / Phenol ether / Halobenzene / Fluorobenzene
show 27 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
aromatic ether, ureas, monochlorobenzenes, monofluorobenzenes, (trifluoromethyl)benzenes, pyridinecarboxamide (CHEBI:68647)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Vegf-b-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell ...
Gene Name
FLT1
Uniprot ID
P17948
Uniprot Name
Vascular endothelial growth factor receptor 1
Molecular Weight
150767.185 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and ...
Gene Name
KDR
Uniprot ID
P35968
Uniprot Name
Vascular endothelial growth factor receptor 2
Molecular Weight
151525.555 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardi...
Gene Name
FLT4
Uniprot ID
P35916
Uniprot Name
Vascular endothelial growth factor receptor 3
Molecular Weight
152755.94 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell main...
Gene Name
KIT
Uniprot ID
P10721
Uniprot Name
Mast/stem cell growth factor receptor Kit
Molecular Weight
109863.655 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chem...
Gene Name
PDGFRA
Uniprot ID
P16234
Uniprot Name
Platelet-derived growth factor receptor alpha
Molecular Weight
122668.46 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Vascular endothelial growth factor binding
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic...
Gene Name
PDGFRB
Uniprot ID
P09619
Uniprot Name
Platelet-derived growth factor receptor beta
Molecular Weight
123966.895 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation ...
Gene Name
FGFR1
Uniprot ID
P11362
Uniprot Name
Fibroblast growth factor receptor 1
Molecular Weight
91866.935 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosi...
Gene Name
FGFR2
Uniprot ID
P21802
Uniprot Name
Fibroblast growth factor receptor 2
Molecular Weight
92024.29 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for ANGPT1, ANGPT2 and ANGPT4 and regulates angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading...
Gene Name
TEK
Uniprot ID
Q02763
Uniprot Name
Angiopoietin-1 receptor
Molecular Weight
125829.005 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Tyrosine kinase that functions as cell surface receptor for fibrillar collagen and regulates cell differentiation, remodeling of the extracellular matrix, cell migration and cell proliferation. Req...
Gene Name
DDR2
Uniprot ID
Q16832
Uniprot Name
Discoidin domain-containing receptor 2
Molecular Weight
96735.44 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympatheti...
Gene Name
NTRK1
Uniprot ID
P04629
Uniprot Name
High affinity nerve growth factor receptor
Molecular Weight
87496.465 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. Th...
Gene Name
EPHA2
Uniprot ID
P29317
Uniprot Name
Ephrin type-A receptor 2
Molecular Weight
108265.585 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein serine/threonine kinase activity
Specific Function
Serine/threonine-protein kinase that acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determin...
Gene Name
RAF1
Uniprot ID
P04049
Uniprot Name
RAF proto-oncogene serine/threonine-protein kinase
Molecular Weight
73051.025 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein serine/threonine kinase activity
Specific Function
Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus. May play a role in the postsynaptic responses of hippocampal neuron. Phosphorylates MAP2K1, a...
Gene Name
BRAF
Uniprot ID
P15056
Uniprot Name
Serine/threonine-protein kinase B-raf
Molecular Weight
84436.135 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein serine/threonine kinase activity
Specific Function
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK11 is one of the four p38 MAPKs which play an important role in the cascades of cellu...
Gene Name
MAPK11
Uniprot ID
Q15759
Uniprot Name
Mitogen-activated protein kinase 11
Molecular Weight
41356.875 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Receptor binding
Specific Function
Non-receptor tyrosine-protein kinase that negatively regulates cell proliferation. Positively regulates PTEN protein stability through phosphorylation of PTEN on 'Tyr-336', which in turn prevents i...
Gene Name
FRK
Uniprot ID
P42685
Uniprot Name
Tyrosine-protein kinase FRK
Molecular Weight
58253.61 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Syntaxin binding
Specific Function
Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility a...
Gene Name
ABL1
Uniprot ID
P00519
Uniprot Name
Tyrosine-protein kinase ABL1
Molecular Weight
122871.435 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell de...
Gene Name
RET
Uniprot ID
P07949
Uniprot Name
Proto-oncogene tyrosine-protein kinase receptor Ret
Molecular Weight
124317.465 Da

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Regorafenib [File]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 2 lacks trans...
Gene Name
UGT1A9
Uniprot ID
O60656
Uniprot Name
UDP-glucuronosyltransferase 1-9
Molecular Weight
59940.495 Da
References
  1. Regorafenib [File]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
References
  1. Regorafenib [File]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Hotta K, Ueyama J, Tatsumi Y, Tsukiyama I, Sugiura Y, Saito H, Matsuura K, Hasegawa T: Lack of Contribution of Multidrug Resistance-associated Protein and Organic Anion-transporting Polypeptide to Pharmacokinetics of Regorafenib, a Novel Multi-Kinase Inhibitor, in Rats. Anticancer Res. 2015 Sep;35(9):4681-9. [PubMed:26254357]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da

Drug created on June 03, 2013 16:30 / Updated on September 21, 2018 00:15