Details of the Drug Combination

General Information of Drug Combination (ID: DCJG7WO)

Drug Combination Name
Regorafenib BAY 86-9766
Indication
Disease Entry Status REF
Neoplasms Phase 1 [1]
Component Drugs Regorafenib   DMHSY1I BAY 86-9766   DMPW5SB
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Regorafenib
Disease Entry ICD 11 Status REF
Gastrointestinal stromal tumour 2B5B Approved [2]
Metastasis from malignant tumor of colon N.A. Approved [2]
Metastatic colorectal cancer 2B91 Approved [3]
Regorafenib Interacts with 3 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Tyrosine-protein kinase Kit (KIT) TTX41N9 KIT_HUMAN Modulator [6]
Proto-oncogene c-Ret (RET) TT4DXQT RET_HUMAN Modulator [6]
Vascular endothelial growth factor receptor 2 (KDR) TTUTJGQ VGFR2_HUMAN Modulator [6]
------------------------------------------------------------------------------------
Regorafenib Interacts with 4 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [7]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [8]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [9]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [7]
------------------------------------------------------------------------------------
Regorafenib Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [10]
UDP-glucuronosyltransferase 1A9 (UGT1A9) DE85D2P UD19_HUMAN Metabolism [10]
------------------------------------------------------------------------------------
Regorafenib Interacts with 11 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [5]
Matrix metalloproteinase-9 (MMP9) OTB2QDAV MMP9_HUMAN Decreases Expression [5]
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Increases Secretion [11]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [5]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Increases Activity [5]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [5]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [5]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [5]
Tumor necrosis factor ligand superfamily member 6 (FASLG) OTZARCHH TNFL6_HUMAN Increases Activity [5]
Transcription factor p65 (RELA) OTUJP9CN TF65_HUMAN Decreases Expression [5]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Activity [5]
------------------------------------------------------------------------------------
⏷ Show the Full List of 11 DOT(s)
Indication(s) of BAY 86-9766
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Phase 3 [4]
BAY 86-9766 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
MAPK/ERK kinase kinase (MAP3K) TTROQ37 NOUNIPROTAC Modulator [12]
------------------------------------------------------------------------------------
BAY 86-9766 Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [13]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [13]
------------------------------------------------------------------------------------

References

1 ClinicalTrials.gov (NCT02168777) Refametinib (BAY86-9766) in Combination With Regorafenib (Stivarga, BAY73-4506) in Patients With Advanced or Metastatic Cancer
2 Regorafenib FDA Label
3 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: 5891).
4 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: 7942).
5 Regorefenib induces extrinsic/intrinsic apoptosis and inhibits MAPK/NF-B-modulated tumor progression in bladder cancer in vitro and in vivo. Environ Toxicol. 2019 Jun;34(6):679-688. doi: 10.1002/tox.22734. Epub 2019 Feb 25.
6 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
7 Regorafenib is transported by the organic anion transporter 1B1 and the multidrug resistance protein 2. Biol Pharm Bull. 2015;38(4):582-6.
8 Brain and Testis Accumulation of Regorafenib is Restricted by Breast Cancer Resistance Protein (BCRP/ABCG2) and P-glycoprotein (P-GP/ABCB1). Pharm Res. 2015 Jul;32(7):2205-16.
9 KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (dg:DG01913)
10 FDA Label of Regorafenib. The 2020 official website of the U.S. Food and Drug Administration.
11 Cytotoxicity of 34 FDA approved small-molecule kinase inhibitors in primary rat and human hepatocytes. Toxicol Lett. 2018 Jul;291:138-148. doi: 10.1016/j.toxlet.2018.04.010. Epub 2018 Apr 12.
12 RDEA119/BAY 869766: a potent, selective, allosteric inhibitor of MEK1/2 for the treatment of cancer.Cancer Res.2009 Sep 1;69(17):6839-47.
13 Multicenter phase I trial of the mitogen-activated protein kinase 1/2 inhibitor BAY 86-9766 in patients with advanced cancer. Clin Cancer Res. 2013 Mar 1;19(5):1232-43.