U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C21H15ClF4N4O3
Molecular Weight 482.815
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of REGORAFENIB

SMILES

CNC(=O)C1=CC(OC2=CC=C(NC(=O)NC3=CC=C(Cl)C(=C3)C(F)(F)F)C(F)=C2)=CC=N1

InChI

InChIKey=FNHKPVJBJVTLMP-UHFFFAOYSA-N
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)

HIDE SMILES / InChI

Molecular Formula C21H15ClF4N4O3
Molecular Weight 482.815
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Regorafenib (trade name Stivarga) is an orally bioavailable small molecule with potential antiangiogenic and antineoplastic activities. Regorafenib binds to and inhibits vascular endothelial growth factor receptors (VEGFRs) 2 and 3, and Ret, Kit, PDGFR and Raf kinases, which may result in the inhibition of tumor angiogenesis and tumor cell proliferation. VEGFRs are receptor tyrosine kinases that play important roles in tumor angiogenesis; the receptor tyrosine kinases RET, KIT, and PDGFR, and the serine/threonine-specific Raf kinase are involved in tumor cell signaling. 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. Since 2009 it was studied as a potential treatment option in multiple tumor types. Stivarga is approved by FDA to treat two different tumor types: metastatic colorectal cancer in patients 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 (approved in 2012) and to treat patients with locally advanced, unresectable or metastatic gastrointestinal stromal tumor who have been previously treated with imatinib mesylate and sunitinib malate (approved in 2013).

CNS Activity

Originator

Approval Year

PubMed

PubMed

TitleDatePubMed
Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity.
2011 Jul 1
Small molecule inhibitors of BRAF in clinical trials.
2012 Jan 15
Regorafenib impairs mitochondrial functions, activates AMP-activated protein kinase, induces autophagy, and causes rat hepatocyte necrosis.
2015 Jan 2
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis.
2015 May 18
Patents

Sample Use Guides

In Vivo Use Guide
160 mg Stivarga orally, once daily for the first 21 days of each 28-day cycle. Take with a low-fat meal.
Route of Administration: Oral
In Vitro Use Guide
For the migration inhibition assay, human lymphatic endothelial cells (LECs) were grown overnight on a gelatin-coated six-well plate, serum starved for 6 hr in EBM-2 media containing 0.1% BSA and treated with 100 nmol/L regorafenib for 1 hr. Regorafenib inhibited the proliferation of 19 cell lines derived from human colon cancers, with IC50 values ranging from 2.6 to 10 umol/L.
Substance Class Chemical
Created
by admin
on Mon Oct 21 21:28:09 UTC 2019
Edited
by admin
on Mon Oct 21 21:28:09 UTC 2019
Record UNII
24T2A1DOYB
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
REGORAFENIB
DASH   INN   ORANGE BOOK   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
BAY 73-4506 MONOHYDRATE
Code English
4-(4-(((4-CHLORO-3-(TRIFLUOROMETHYL)PHENYL)CARBAMOYL)AMINO)-3-FLUOROPHENOXY)-N-METHYLPYRIDINE-2-CARBOXAMIDE
Systematic Name English
REGORAFENIB [WHO-DD]
Common Name English
BAY 73-4506
Code English
BAY-734506
Code English
REGORAFENIB [VANDF]
Common Name English
REGORAFENIB [INN]
Common Name English
STIVARGA
Brand Name English
REGORAFENIB [USAN]
Common Name English
REGORAFENIB [MI]
Common Name English
REGORAFENIB [ORANGE BOOK]
Common Name English
BAY-73-4506
Code English
Classification Tree Code System Code
NCI_THESAURUS C1742
Created by admin on Mon Oct 21 21:28:09 UTC 2019 , Edited by admin on Mon Oct 21 21:28:09 UTC 2019
WHO-ATC L01XE21
Created by admin on Mon Oct 21 21:28:09 UTC 2019 , Edited by admin on Mon Oct 21 21:28:09 UTC 2019
FDA ORPHAN DRUG 329410
Created by admin on Mon Oct 21 21:28:09 UTC 2019 , Edited by admin on Mon Oct 21 21:28:09 UTC 2019
NCI_THESAURUS C1404
Created by admin on Mon Oct 21 21:28:09 UTC 2019 , Edited by admin on Mon Oct 21 21:28:09 UTC 2019
NCI_THESAURUS C129825
Created by admin on Mon Oct 21 21:28:09 UTC 2019 , Edited by admin on Mon Oct 21 21:28:09 UTC 2019
LIVERTOX 839
Created by admin on Mon Oct 21 21:28:09 UTC 2019 , Edited by admin on Mon Oct 21 21:28:09 UTC 2019
EMA ASSESSMENT REPORTS STIVARGA (AUTHORIZED: COLORECTAL NEOPLASMS)
Created by admin on Mon Oct 21 21:28:09 UTC 2019 , Edited by admin on Mon Oct 21 21:28:09 UTC 2019
NDF-RT N0000175605
Created by admin on Mon Oct 21 21:28:09 UTC 2019 , Edited by admin on Mon Oct 21 21:28:09 UTC 2019
WHO-VATC QL01XE21
Created by admin on Mon Oct 21 21:28:09 UTC 2019 , Edited by admin on Mon Oct 21 21:28:09 UTC 2019
FDA ORPHAN DRUG 478015
Created by admin on Mon Oct 21 21:28:09 UTC 2019 , Edited by admin on Mon Oct 21 21:28:09 UTC 2019
Code System Code Type Description
WIKIPEDIA
Regorafenib
Created by admin on Mon Oct 21 21:28:09 UTC 2019 , Edited by admin on Mon Oct 21 21:28:09 UTC 2019
PRIMARY
CAS
755037-03-7
Created by admin on Mon Oct 21 21:28:09 UTC 2019 , Edited by admin on Mon Oct 21 21:28:09 UTC 2019
PRIMARY
IUPHAR
5891
Created by admin on Mon Oct 21 21:28:09 UTC 2019 , Edited by admin on Mon Oct 21 21:28:09 UTC 2019
PRIMARY
DRUG BANK
DB08896
Created by admin on Mon Oct 21 21:28:09 UTC 2019 , Edited by admin on Mon Oct 21 21:28:09 UTC 2019
PRIMARY
EVMPD
SUB73090
Created by admin on Mon Oct 21 21:28:09 UTC 2019 , Edited by admin on Mon Oct 21 21:28:09 UTC 2019
PRIMARY
NCI_THESAURUS
C78204
Created by admin on Mon Oct 21 21:28:09 UTC 2019 , Edited by admin on Mon Oct 21 21:28:09 UTC 2019
PRIMARY
PUBCHEM
11167602
Created by admin on Mon Oct 21 21:28:09 UTC 2019 , Edited by admin on Mon Oct 21 21:28:09 UTC 2019
PRIMARY
RXCUI
1312397
Created by admin on Mon Oct 21 21:28:09 UTC 2019 , Edited by admin on Mon Oct 21 21:28:09 UTC 2019
PRIMARY RxNorm
ChEMBL
CHEMBL1946170
Created by admin on Mon Oct 21 21:28:09 UTC 2019 , Edited by admin on Mon Oct 21 21:28:09 UTC 2019
PRIMARY
MERCK INDEX
M11701
Created by admin on Mon Oct 21 21:28:09 UTC 2019 , Edited by admin on Mon Oct 21 21:28:09 UTC 2019
PRIMARY
EPA CompTox
755037-03-7
Created by admin on Mon Oct 21 21:28:09 UTC 2019 , Edited by admin on Mon Oct 21 21:28:09 UTC 2019
PRIMARY
LactMed
755037-03-7
Created by admin on Mon Oct 21 21:28:09 UTC 2019 , Edited by admin on Mon Oct 21 21:28:09 UTC 2019
PRIMARY
MESH
C559147
Created by admin on Mon Oct 21 21:28:09 UTC 2019 , Edited by admin on Mon Oct 21 21:28:09 UTC 2019
PRIMARY
NDF-RT
N0000185504
Created by admin on Mon Oct 21 21:28:09 UTC 2019 , Edited by admin on Mon Oct 21 21:28:09 UTC 2019
PRIMARY Cytochrome P450 2C9 Inhibitors [MoA]
INN
9026
Created by admin on Mon Oct 21 21:28:09 UTC 2019 , Edited by admin on Mon Oct 21 21:28:09 UTC 2019
PRIMARY
Related Record Type Details
TRANSPORTER -> INHIBITOR
Regorafenib inhibits Pgp and BCRP in vitro.
TRANSPORTER -> INHIBITOR
Regorafenib inhibits Pgp and BCRP in vitro.
TARGET -> INHIBITOR
BINDER->LIGAND
BINDING
TARGET -> INHIBITOR
METABOLIC ENZYME -> SUBSTRATE
SALT/SOLVATE -> PARENT
Related Record Type Details
METABOLITE INACTIVE -> PARENT
METABOLITE ACTIVE -> PARENT
MAJOR
PLASMA
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC SINGLE DOSE

Tmax PHARMACOKINETIC SINGLE DOSE