Details of the Drug Combination

General Information of Drug Combination (ID: DCR72MH)

Drug Combination Name
Regorafenib Perindopril
Indication
Disease Entry Status REF
Metastatic Colorectal Cancer Phase 2 [1]
Component Drugs Regorafenib   DMHSY1I Perindopril   DMOPZDT
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 6 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [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]
Tumor necrosis factor ligand superfamily member 6 (FASLG) OTZARCHH TNFL6_HUMAN Increases Activity [5]
Transcription factor p65 (RELA) OTUJP9CN TF65_HUMAN Decreases Expression [5]
------------------------------------------------------------------------------------
⏷ Show the Full List of 6 DOT(s)
Indication(s) of Perindopril
Disease Entry ICD 11 Status REF
Hypertension BA00-BA04 Approved [4]
Perindopril Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Angiotensin-converting enzyme (ACE) TTL69WB ACE_HUMAN Inhibitor [12]
------------------------------------------------------------------------------------
Perindopril Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Peptide transporter 1 (SLC15A1) DT9G7XN S15A1_HUMAN Substrate [13]
Peptide transporter 2 (SLC15A2) DT8QKNP S15A2_HUMAN Substrate [13]
------------------------------------------------------------------------------------
Perindopril Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Renin (REN) OT52GZR2 RENI_HUMAN Increases Activity [14]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Decreases Expression [15]
------------------------------------------------------------------------------------

References

1 ClinicalTrials.gov (NCT02651415) Phase II Study of Perindopril and Regorafenib in mCRC
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: 6367).
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 Angiotensin-converting enzyme activity is involved in the mechanism of increased endogenous nitric oxide synthase inhibitor in patients with type 2 diabetes mellitus. Circ J. 2002 Sep;66(9):811-5. doi: 10.1253/circj.66.811.
12 Fixed combination perindopril-amlodipine (Coveram) in the treatment of hypertension and coronary heart disease. Rev Med Liege. 2009 Apr;64(4):223-7.
13 Transport of angiotensin-converting enzyme inhibitors by H+/peptide transporters revisited. J Pharmacol Exp Ther. 2008 Nov;327(2):432-41.
14 Experience with perindopril in normal volunteers. Arch Mal Coeur Vaiss. 1989 May;82 Spec No 1:35-41.
15 The effects of 1 month antihypertensive treatment with perindopril, bisoprolol or both on the ex vivo ability of monocytes to secrete inflammatory cytokines. Int J Clin Pharmacol Ther. 2009 Nov;47(11):686-94. doi: 10.5414/cpp47686.