Details of the Drug-Related molecule(s) Expression Atlas

General Information of Drug (ID: DMS8IFC)

Drug Name
Sorafenib Drug Info
Synonyms
Nexavar; Sorafenibum; Sorafenib [INN]; Nexavar (TN); Sorafenib (INN); N-[4-Chloro-3-(trifluoromethyl)phenyl]-N'-[4-[2-(N-methylcarbamoyl)-4-pyridyloxy]phenyl]urea; N-(4-Chloro-3-(trifluoromethyl)phenyl)-N'-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl)urea; N-(4-chloro-3-(trifluoromethyl)phenyl)-N'-(4-(2-(N-methylcar bamoyl)-4-pyridyloxy)phenyl)urea; 4(4-{3-[4-Chloro-3-(trifluoromethyl)phenyl]ureido}phenoxy)-N(sup 2)-methylpyridine-2-carboxamide; 4-(4-((((4-Chloro-3-(trifluoromethyl)phenyl)amino)carbonyl)amino)phenoxy)-N-methyl-2-pyridinecarboxamide; 4-(4-(3-(4-chloro-3-trifluoromethylphenyl)ureido)phenoxy)pyridine-2-carboxyllic acid methyamide-4-methylbenzenesulfonate; 4-(4-{3-(4-Chloro-3-(trifluoromethyl)phenyl)ureido}phenoxy)-N(sup 2)-methylpyridine-2-carboxamide; 4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-N-methylpyridine-2-carboxamide; 4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]-N-methyl-pyridine-2-carboxamide; 4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]-N-methylpyridine-2-carboxamide; 4-[4-[[[[4-chloro-3-(trifluoromethyl)phenyl]amino]carbonyl]amino]phenoxy]-N-methyl-2-pyridinecarboxamide; 4-{4-[({[4-CHLORO-3-(TRIFLUOROMETHYL)PHENYL]AMINO}CARBONYL)AMINO]PHENOXY}-N-METHYLPYRIDINE-2-CARBOXAMIDE; Sorafenib (Pan-TK inhibitor)
Indication
Disease Entry ICD 11 Status REF
Adenocarcinoma 2D40 Approved [1]
Carcinoma 2A00-2F9Z Approved [1]
Clear cell renal carcinoma Approved [1]
Lung cancer 2C25.0 Approved [1]
Medullary thyroid gland carcinoma Approved [1]
Non-small-cell lung cancer 2C25.Y Approved [1]
Renal cell carcinoma 2C90 Approved [2]
Thyroid cancer 2D10 Approved [1]
Hepatocellular carcinoma 2C12.02 Phase 3 [2]
Myelodysplastic syndrome 2A37 Phase 2 [2]
Therapeutic Class
Anticancer Agents
Cross-matching ID
PubChem CID
216239
ChEBI ID
CHEBI:50924
CAS Number
CAS 284461-73-0
TTD Drug ID
DMS8IFC
VARIDT Drug ID
DR00304
INTEDE Drug ID
DR1500
ACDINA Drug ID
D00635

Molecule(s) Related to This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Epidermal growth factor receptor (EGFR) TTGKNB4 EGFR_HUMAN Inhibitor [3]
Platelet-derived growth factor receptor beta (PDGFRB) TTI7421 PGFRB_HUMAN Modulator [4]
Tyrosine-protein kinase Kit (KIT) TTX41N9 KIT_HUMAN Modulator [4]
Vascular endothelial growth factor receptor 2 (KDR) TTUTJGQ VGFR2_HUMAN Modulator [4]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID Highest Status REF
RalBP1-associated Eps domain-containing protein 2 (RALBP1) DTYEM9B REPS2_HUMAN Approved [5]
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Approved [6]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Approved [7]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Approved [8]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Approved [9]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Approved [9]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Approved [10]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID Highest Status REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Approved [11]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Approved [12]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Approved [13]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Approved [11]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Approved [13]
UDP-glucuronosyltransferase 1A9 (UGT1A9) DE85D2P UD19_HUMAN Approved [14]

The Expression Level of Molecule(s) in Normal Tissue of Major ADME-Related Organs

Molecule Molecule Type Gene Name Liver Colon Kidney Small Intestine
Tyrosine-protein kinase Kit (KIT) DTT KIT 3.766 7.517 7.379 6.916
Platelet-derived growth factor receptor beta (PDGFRB) DTT PDGFRB 6.43 6.333 6.671 5.97
Epidermal growth factor receptor (EGFR) DTT EGFR 6.045 4.991 5.317 5.252
P-glycoprotein 1 (ABCB1) DTP P-GP 7.009 6.988 7.442 8.135
Organic cation transporter 1 (SLC22A1) DTP `OCT1 10.261 4.162 4.07 3.797
Breast cancer resistance protein (ABCG2) DTP BCRP 6.732 7.513 6.326 9.277
Multidrug resistance-associated protein 2 (ABCC2) DTP MRP2 7.751 4.17 6.425 6.282
Organic anion transporting polypeptide 1B3 (SLCO1B3) DTP OATP1B3 8.873 2.17 2.485 3.322
Organic anion transporting polypeptide 1B1 (SLCO1B1) DTP OATP1B1 9.79 0.485 3.511 2.07
Cytochrome P450 2C8 (CYP2C8) DME CYP2C8 9.791 3.744 3.413 1.609
Cytochrome P450 1A2 (CYP1A2) DME CYP1A2 10.036 5.779 6.508 6.481
Cytochrome P450 3A5 (CYP3A5) DME CYP3A5 10.08 7.207 5.403 9.211
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 11.692 6.58 4.984 9.089
Molecule Expression Atlas in Normal Tissue of Major ADME-related organs

The Expression Level of Molecule(s) between Disease Section and Healthy Individual Tissue

The Studied Disease Adenocarcinoma
ICD Disease Classification 2D40
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Tyrosine-protein kinase Kit (KIT) DTT KIT 1.26E-09 -0.44 -0.75
Vascular endothelial growth factor receptor 2 (KDR) DTT KDR 7.27E-04 0.26 0.31
Platelet-derived growth factor receptor beta (PDGFRB) DTT PDGFRB 1.95E-31 1.69 1.65
Epidermal growth factor receptor (EGFR) DTT EGFR 5.84E-05 0.32 0.55
P-glycoprotein 1 (ABCB1) DTP P-GP 1.42E-02 -2.10E-01 -5.11E-01
Organic cation transporter 1 (SLC22A1) DTP SLC22A1 1.94E-08 1.59E-01 6.93E-01
Breast cancer resistance protein (ABCG2) DTP BCRP 1.07E-06 -3.94E-01 -6.94E-01
Multidrug resistance-associated protein 2 (ABCC2) DTP MRP2 5.32E-02 -1.36E-01 -2.97E-01
Organic anion transporting polypeptide 1B3 (SLCO1B3) DTP OATP1B3 1.86E-13 4.08E-01 7.55E-01
Organic anion transporting polypeptide 1B1 (SLCO1B1) DTP OATP1B1 8.73E-01 1.50E-03 9.14E-03
Cytochrome P450 2C8 (CYP2C8) DME CYP2C8 2.90E-11 -1.06E-01 -1.42E-01
Cytochrome P450 1A2 (CYP1A2) DME CYP1A2 7.26E-01 -3.16E-02 -1.31E-01
Cytochrome P450 3A5 (CYP3A5) DME CYP3A5 2.45E-13 -2.29E+00 -1.44E+00
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 5.04E-04 -9.90E-02 -3.91E-01
Molecular Expression Atlas between Disease Section and Healthy Individual Tissue

References

1 Sorafenib FDA Label
2 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5711).
3 Nasopharyngeal carcinoma: Current treatment options and future directions. J Nasopharyng Carcinoma, 2014, 1(16): e16.
4 Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling.Mol Cancer Ther.2008 Oct;7(10):3129-40.
5 Rlip76 transports sunitinib and sorafenib and mediates drug resistance in kidney cancer. Int J Cancer. 2010 Mar 15;126(6):1327-38.
6 Multidrug resistance protein 2 implicates anticancer drug-resistance to sorafenib. Biol Pharm Bull. 2011;34(3):433-5.
7 Upregulation of histone acetylation reverses organic anion transporter 2 repression and enhances 5-fluorouracil sensitivity in hepatocellular carcinoma
8 Double-transduced MDCKII cells to study human P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) interplay in drug transport across the blood-brain barrier. Mol Pharm. 2011 Apr 4;8(2):571-82.
9 Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Clin Cancer Res. 2013 Mar 15;19(6):1458-66.
10 Breast cancer resistance protein and P-glycoprotein limit sorafenib brain accumulation. Mol Cancer Ther. 2010 Feb;9(2):319-26.
11 Interaction of sorafenib and cytochrome P450 isoenzymes in patients with advanced melanoma: a phase I/II pharmacokinetic interaction study. Cancer Chemother Pharmacol. 2011 Nov;68(5):1111-8.
12 Ontogeny and sorafenib metabolism. Clin Cancer Res. 2012 Oct 15;18(20):5788-95.
13 Drug Interactions Flockhart Table
14 Pharmacokinetic interaction involving sorafenib and the calcium-channel blocker felodipine in a patient with hepatocellular carcinoma. Invest New Drugs. 2011 Dec;29(6):1511-4.