Details of the Drug Combination

General Information of Drug Combination (ID: DCSKBNL)

• Drug Combination Name: Oxaliplatin + Aflibercept
• Indication: Colorectal Cancer Metastatic; Status: Phase 1 [1]
• Component Drugs:
  Oxaliplatin (DMQNWRD): Small molecular drug
  Aflibercept (DMT3D5I): N.A.

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Oxaliplatin

Disease Entry	ICD 11	Status	REF
Adenocarcinoma	2D40	Approved	[2]
Appendiceal neoplasm	N.A.	Approved	[2]
Cholangiocarcinoma	2C12.10	Approved	[2]
Colon adenocarcinoma	N.A.	Approved	[2]
Colorectal cancer	2B91.Z	Approved	[3]
Colorectal carcinoma	N.A.	Approved	[2]
Endocrine gland neoplasm	N.A.	Approved	[2]
Gallbladder carcinoma	N.A.	Approved	[2]
Metastasis from malignant tumor of colon	N.A.	Approved	[2]
Nasopharyngeal carcinoma	2B6B	Approved	[2]
Peritoneal neoplasm	N.A.	Approved	[2]
Rectal adenocarcinoma	2B92	Approved	[2]
Rectal neoplasm	N.A.	Approved	[2]
Rectum mucinous adenocarcinoma	N.A.	Approved	[2]
Colon cancer	2B90.Z	Investigative	[2]
Gastric cancer	2B72	Investigative	[2]

Oxaliplatin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Modulator	[9]

Oxaliplatin Interacts with 5 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[10]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[11]
Organic cation transporter 2 (SLC22A2)	DT9IDPW	S22A2_HUMAN	Substrate	[12]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[13]
High affinity copper uptake protein 1 (SLC31A1)	DTP8L4F	COPT1_HUMAN	Substrate	[14]

Oxaliplatin Interacts with 12 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[15]
Cytochrome P450 1A1 (CYP1A1)	DE6OQ3W	CP1A1_HUMAN	Metabolism	[15]
Cytochrome P450 2E1 (CYP2E1)	DEVDYN7	CP2E1_HUMAN	Metabolism	[15]
Cytochrome P450 1B1 (CYP1B1)	DE9QHP6	CP1B1_HUMAN	Metabolism	[15]
Glutathione S-transferase pi (GSTP1)	DEK6079	GSTP1_HUMAN	Metabolism	[16]
Glutathione S-transferase theta-1 (GSTT1)	DE3PKUG	GSTT1_HUMAN	Metabolism	[16]
Metallothionein-1A (MT1A)	DE5ME8A	MT1A_HUMAN	Metabolism	[16]
Metallothionein-2A (MT2A)	DEFKGT7	MT2_HUMAN	Metabolism	[16]
Myeloperoxidase (MPO)	DEA3U9Y	PERM_HUMAN	Metabolism	[16]
Quinone reductase 1 (NQO1)	DENP5RY	NQO1_HUMAN	Metabolism	[16]
Superoxide dismutase 1 (SOD1)	DEUTDON	SODC_HUMAN	Metabolism	[16]
Glutathione S-transferase mu-1 (GSTM1)	DEYZEJA	GSTM1_HUMAN	Metabolism	[16]

Oxaliplatin Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Protachykinin-1 (TAC1)	OTM842YW	TKN1_HUMAN	Increases ADR	[17]

Indication(s) of Aflibercept

Disease Entry	ICD 11	Status	REF
Central retinal vein occlusion with macular edema	N.A.	Approved	[4]
Diabetic macular edema	9B71.02	Approved	[5]
Exudative age-related macular degeneration	9B78.3Z	Approved	[6]
Metastasis from malignant tumor of colon	N.A.	Approved	[7]
Metastatic colorectal cancer	2B91	Approved	[8]

Aflibercept Interacts with 3 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Vascular endothelial growth factor A (VEGFA)	TTOHSBA	VEGFA_HUMAN	Modulator	[8]
Vascular endothelial growth factor B (VEGFB)	TTPJQHE	VEGFB_HUMAN	Modulator	[8]
Placenta growth factor (PlGF)	TT48I1Y	PLGF_HUMAN	Modulator	[8]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Rectal Cancer	DCUA8H4	N. A.	Phase 1	[18]

References

• [1] ClinicalTrials.gov (NCT01955629) Study of Aflibercept as Maintenance Therapy Following Induction With Aflibercept in Combination With XELOX, as First-Line Treatment for Metastatic Colorectal Cancer Patient
• [2] Oxaliplatin 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: 7433).
• [4] A review of neovascular glaucoma. Etiopathogenesis and treatment. Rom J Ophthalmol. 2021 Oct-Dec;65(4):315-329.
• [5] Aflibercept versus Faricimab in the Treatment of Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema: A Review. Int J Mol Sci. 2022 Aug 20;23(16):9424.
• [6] Efficacy and Safety of Intravitreal Aflibercept Treat-and-Extend Regimens in Exudative Age-Related Macular Degeneration: 52- and 96-Week Findings from ALTAIR : A Randomized Controlled Trial. Adv Ther. 2020 Mar;37(3):1173-1187.
• [7] A Comparison of Folinic Acid, Fluorouracil and Irinotecan (FOLFIRI) plus Bevacizumab and FOLFIRI plus Aflibercept as Second-line Treatment for Metastatic Colorectal Cancer. Clin Oncol (R Coll Radiol). 2022 Aug;34(8):e323-e328.
• [8] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [9] Structures of oxaliplatin-oligonucleotide adducts from DNA.J Mass Spectrom.2012 Oct;47(10):1282-93.
• [10] Multidrug Resistance-Associated Protein 2 (MRP2) Mediated Transport of Oxaliplatin-Derived Platinum in Membrane Vesicles. PLoS One. 2015 Jul 1;10(7):e0130727.
• [11] Effect of ABCG2 on cytotoxicity of platinum drugs: interference of EGFP. Toxicol In Vitro. 2008 Dec;22(8):1846-52.
• [12] Relevance of copper transporter 1 and organic cation transporters 1-3 for oxaliplatin uptake and drug resistance in colorectal cancer cells. Metallomics. 2018 Mar 1;10(3):414-425.
• [13] Organic cation transporters are determinants of oxaliplatin cytotoxicity. Cancer Res. 2006 Sep 1;66(17):8847-57.
• [14] Copper transporters regulate the cellular pharmacology and sensitivity to Pt drugs. Crit Rev Oncol Hematol. 2005 Jan;53(1):13-23.
• [15] The influence of metabolic gene polymorphisms on urinary 1-hydroxypyrene concentrations in Chinese coke oven workers. Sci Total Environ. 2007 Aug 1;381(1-3):38-46.
• [16] PharmGKB: A worldwide resource for pharmacogenomic information. Wiley Interdiscip Rev Syst Biol Med. 2018 Jul;10(4):e1417. (ID: PA150642262)
• [17] Polymorphic markers associated with severe oxaliplatin-induced, chronic peripheral neuropathy in colon cancer patients. Cancer. 2012 Jun 1;118(11):2828-36. doi: 10.1002/cncr.26614. Epub 2011 Oct 21.
• [18] ClinicalTrials.gov (NCT01749956) 5-FU, Aflibercept, and Radiation (RT) for Preoperative and Postoperative Patients With Stage II/III Rectal Cancer