Details of the Drug

General Information of Drug (ID: DMHSY1I)

Drug Name
Regorafenib
Synonyms
Regorafenib; 755037-03-7; BAY 73-4506; Regorafenibum; Stivarga; 4-(4-(3-(4-Chloro-3-(trifluoromethyl)phenyl)ureido)-3-fluorophenoxy)-N-methylpicolinamide; BAY73-4506; Regorafenib (BAY 73-4506); UNII-24T2A1DOYB; 4-[4-({[4-Chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide; BAY-73-4506; 24T2A1DOYB; CHEMBL1946170; CHEBI:68647; Stivarga (TN); BAY73-4506 hydrochloride; Regorafenib [USAN:INN]
Indication
Disease Entry ICD 11 Status REF
Metastatic colorectal cancer 2B91 Approved [1], [2]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 482.8
Topological Polar Surface Area (xlogp) 4.2
Rotatable Bond Count (rotbonds) 5
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 8
ADMET Property
Absorption AUC
The area under the plot of plasma concentration (AUC) of drug is 70.4 mgh/L [3]
Absorption Cmax
The maximum plasma concentration (Cmax) of drug is 2.5 mg/L [3]
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 4 h [3]
Half-life
The concentration or amount of drug in body reduced by one-half in 28 hours [4]
Metabolism
The drug is metabolized via the CYP3A4 and UGT1A9 [5]
Chemical Identifiers
Formula
C21H15ClF4N4O3
IUPAC Name
4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]-3-fluorophenoxy]-N-methylpyridine-2-carboxamide
Canonical SMILES
CNC(=O)C1=NC=CC(=C1)OC2=CC(=C(C=C2)NC(=O)NC3=CC(=C(C=C3)Cl)C(F)(F)F)F
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)
InChIKey
FNHKPVJBJVTLMP-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
11167602
ChEBI ID
CHEBI:68647
CAS Number
755037-03-7
DrugBank ID
DB08896
TTD ID
D09GDD
VARIDT ID
DR00136
INTEDE ID
DR1401
ACDINA ID
D00586

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Proto-oncogene c-Ret (RET) TT4DXQT RET_HUMAN Modulator [6]
Tyrosine-protein kinase Kit (KIT) TTX41N9 KIT_HUMAN Modulator [6]
Vascular endothelial growth factor receptor 2 (KDR) TTUTJGQ VGFR2_HUMAN Modulator [6]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [7]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [8]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [7]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [9]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4)
Main DME 		DE4LYSA CP3A4_HUMAN Substrate [10]
UDP-glucuronosyltransferase 1A9 (UGT1A9)
Main DME 		DE85D2P UD19_HUMAN Substrate [10]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Metastatic colorectal cancer
ICD Disease Classification 2B91
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Tyrosine-protein kinase Kit (KIT) DTT KIT 2.06E-01 -0.1 -0.14
Vascular endothelial growth factor receptor 2 (KDR) DTT KDR 1.98E-01 0.11 0.2
P-glycoprotein 1 (ABCB1) DTP P-GP 9.39E-02 1.07E-01 2.80E-01
Breast cancer resistance protein (ABCG2) DTP BCRP 9.45E-01 -5.34E-02 -9.01E-02
Multidrug resistance-associated protein 2 (ABCC2) DTP MRP2 7.16E-01 -1.28E-02 -6.06E-02
Organic anion transporting polypeptide 1B1 (SLCO1B1) DTP OATP1B1 8.15E-01 6.20E-03 5.61E-02
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 1.04E-02 6.29E-02 3.54E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Regorafenib (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Remdesivir DMBFZ6L Moderate Increased risk of hepatotoxicity by the combination of Regorafenib and Remdesivir. 1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019] [82]
Arn-509 DMT81LZ Moderate Increased metabolism of Regorafenib caused by Arn-509 mediated induction of CYP450 enzyme. Acute myeloid leukaemia [2A60] [83]
Bedaquiline DM3906J Moderate Increased risk of hepatotoxicity by the combination of Regorafenib and Bedaquiline. Antimicrobial drug resistance [MG50-MG52] [84]
Troleandomycin DMUZNIG Moderate Decreased metabolism of Regorafenib caused by Troleandomycin mediated inhibition of CYP450 enzyme. Bacterial infection [1A00-1C4Z] [82]
Pexidartinib DMS2J0Z Major Decreased metabolism of Regorafenib caused by Pexidartinib mediated inhibition of CYP450 enzyme. Bone/articular cartilage neoplasm [2F7B] [85]
Talazoparib DM1KS78 Moderate Decreased clearance of Regorafenib due to the transporter inhibition by Talazoparib. Breast cancer [2C60-2C6Y] [86]
Tucatinib DMBESUA Moderate Decreased metabolism of Regorafenib caused by Tucatinib mediated inhibition of CYP450 enzyme. Breast cancer [2C60-2C6Y] [82]
Levomilnacipran DMV26S8 Moderate Increased risk of bleeding by the combination of Regorafenib and Levomilnacipran. Chronic pain [MG30] [87]
Lumacaftor DMCLWDJ Moderate Increased metabolism of Regorafenib caused by Lumacaftor mediated induction of CYP450 enzyme. Cystic fibrosis [CA25] [88]
Vortioxetine DM6F1PU Moderate Increased risk of bleeding by the combination of Regorafenib and Vortioxetine. Depression [6A70-6A7Z] [87]
Cannabidiol DM0659E Moderate Increased risk of hepatotoxicity by the combination of Regorafenib and Cannabidiol. Epileptic encephalopathy [8A62] [89]
Tazemetostat DMWP1BH Major Increased risk of bleeding by the combination of Regorafenib and Tazemetostat. Follicular lymphoma [2A80] [89]
Avapritinib DMK2GZX Major Increased risk of bleeding by the combination of Regorafenib and Avapritinib. Gastrointestinal stromal tumour [2B5B] [89]
Cobicistat DM6L4H2 Moderate Decreased metabolism of Regorafenib caused by Cobicistat mediated inhibition of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [82]
Dolutegravir DMCZGRE Minor Decreased metabolism of Regorafenib caused by Dolutegravir mediated inhibition of UGT. Human immunodeficiency virus disease [1C60-1C62] [90]
Berotralstat DMWA2DZ Major Decreased clearance of Regorafenib due to the transporter inhibition by Berotralstat. Innate/adaptive immunodeficiency [4A00] [91]
Naloxegol DML0B41 Minor Decreased clearance of Regorafenib due to the transporter inhibition by Naloxegol. Large intestine motility disorder [DB32] [92]
Ceritinib DMB920Z Moderate Decreased metabolism of Regorafenib caused by Ceritinib mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [82]
PF-06463922 DMKM7EW Moderate Increased metabolism of Regorafenib caused by PF-06463922 mediated induction of CYP450 enzyme. Lung cancer [2C25] [93]
Selpercatinib DMZR15V Moderate Decreased metabolism of Regorafenib caused by Selpercatinib mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [94]
Calaspargase pegol DMQZBXI Moderate Increased risk of hepatotoxicity by the combination of Regorafenib and Calaspargase pegol. Malignant haematopoietic neoplasm [2B33] [95]
Idelalisib DM602WT Moderate Increased risk of hepatotoxicity by the combination of Regorafenib and Idelalisib. Mature B-cell leukaemia [2A82] [96]
GDC-0199 DMH0QKA Major Decreased clearance of Regorafenib due to the transporter inhibition by GDC-0199. Mature B-cell leukaemia [2A82] [82]
IPI-145 DMWA24P Moderate Decreased metabolism of Regorafenib caused by IPI-145 mediated inhibition of CYP450 enzyme. Mature B-cell leukaemia [2A82] [97]
Acalabrutinib DM7GCVW Major Increased risk of bleeding by the combination of Regorafenib and Acalabrutinib. Mature B-cell lymphoma [2A85] [89]
Ibrutinib DMHZCPO Major Increased risk of bleeding by the combination of Regorafenib and Ibrutinib. Mature B-cell lymphoma [2A85] [89]
Ponatinib DMYGJQO Major Increased risk of bleeding by the combination of Regorafenib and Ponatinib. Mature B-cell lymphoma [2A85] [89]
Arry-162 DM1P6FR Major Increased risk of bleeding by the combination of Regorafenib and Arry-162. Melanoma [2C30] [89]
LGX818 DMNQXV8 Major Increased risk of bleeding by the combination of Regorafenib and LGX818. Melanoma [2C30] [89]
Dabrafenib DMX6OE3 Moderate Increased metabolism of Regorafenib caused by Dabrafenib mediated induction of CYP450 enzyme. Melanoma [2C30] [89]
Ubrogepant DM749I3 Moderate Decreased clearance of Regorafenib due to the transporter inhibition by Ubrogepant. Migraine [8A80] [98]
Rimegepant DMHOAUG Moderate Decreased clearance of Regorafenib due to the transporter inhibition by Rimegepant. Migraine [8A80] [99]
Fedratinib DM4ZBK6 Major Increased risk of bleeding by the combination of Regorafenib and Fedratinib. Myeloproliferative neoplasm [2A20] [89]
Vorapaxar DMA16BR Major Increased risk of bleeding by the combination of Regorafenib and Vorapaxar. Myocardial infarction [BA41-BA43] [89]
Abametapir DM2RX0I Moderate Decreased metabolism of Regorafenib caused by Abametapir mediated inhibition of CYP450 enzyme. Pediculosis [1G00] [100]
Lefamulin DME6G97 Moderate Decreased metabolism of Regorafenib caused by Lefamulin mediated inhibition of CYP450 enzyme. Pneumonia [CA40] [101]
Enzalutamide DMGL19D Moderate Increased metabolism of Regorafenib caused by Enzalutamide mediated induction of CYP450 enzyme. Prostate cancer [2C82] [83]
Larotrectinib DM26CQR Moderate Decreased metabolism of Regorafenib caused by Larotrectinib mediated inhibition of CYP450 enzyme. Solid tumour/cancer [2A00-2F9Z] [82]
Fostamatinib DM6AUHV Moderate Decreased clearance of Regorafenib due to the transporter inhibition by Fostamatinib. Thrombocytopenia [3B64] [102]
Lusutrombopag DMH6IKO Moderate Decreased clearance of Regorafenib due to the transporter inhibition by Lusutrombopag. Thrombocytopenia [3B64] [103]
Betrixaban DM2C4RF Major Increased risk of bleeding by the combination of Regorafenib and Betrixaban. Venous thromboembolism [BD72] [89]
⏷ Show the Full List of 41 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
Carmellose sodium E00625 Not Available Disintegrant
Eisenoxyd E00585 56841934 Colorant
Ferric hydroxide oxide yellow E00539 23320441 Colorant
Magnesium stearate E00208 11177 lubricant
Polyethylene glycol 3350 E00652 Not Available Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Silicon dioxide E00670 Not Available Anticaking agent; Opacifying agent; Viscosity-controlling agent
Soybean lecithin E00637 Not Available Other agent
Talc E00520 16211421 Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide E00322 26042 Coating agent; Colorant; Opacifying agent
⏷ Show the Full List of 9 Pharmaceutical Excipients of This Drug
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Regorafenib 40 mg tablet 40 mg Oral Tablet Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

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