Details of the Drug Combination

General Information of Drug Combination (ID: DC7YVGZ)

• Drug Combination Name: Pirfenidone + Nintedanib
• Indication: Idiopathic Pulmonary Fibrosis; Status: Phase 4 [1]
• Component Drugs:
  Pirfenidone (DM6VZFQ): Small molecular drug
  Nintedanib (DMMQ2OW): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Pirfenidone

Disease Entry	ICD 11	Status	REF
Idiopathic pulmonary fibrosis	CB03.4	Approved	[2]

Pirfenidone Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Transforming growth factor beta 1 (TGFB1)	TTR9XHZ	TGFB1_HUMAN	Modulator	[6]

Pirfenidone Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[7]

Pirfenidone Interacts with 4 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[8]
Collagen alpha-1(I) chain (COL1A1)	OTI31178	CO1A1_HUMAN	Decreases Expression	[9]
Actin, aortic smooth muscle (ACTA2)	OTEDLG8E	ACTA_HUMAN	Decreases Expression	[10]
Histone deacetylase 9 (HDAC9)	OTO8O0LF	HDAC9_HUMAN	Decreases Expression	[8]

Indication(s) of Nintedanib

Disease Entry	ICD 11	Status	REF
Idiopathic pulmonary fibrosis	CB03.4	Approved	[3]
Non-small-cell lung cancer	2C25.Y	Approved	[4]
Ovarian neoplasm	N.A.	Approved	[4]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[5]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Pulmonary Fibrosis	DCTN4WO	N. A.	Phase 1	[11]

References

• [1] ClinicalTrials.gov (NCT02606877) A Study to Compare the Amount of Nintedanib and Pirfenidone in the Blood When Nintedanib and Pirfenidone Are Given Separately or in Combination
• [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: 7532).
• [3] FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (NDA) 205832
• [4] Nintedanib FDA Label
• [5] ClinicalTrials.gov (NCT04338802) Efficacy and Safety of Nintedanib in the Treatment of Pulmonary Fibrosis in Patients With Moderate to Severe COVID -19. U.S. National Institutes of Health.
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [7] Risk of clinically relevant pharmacokinetic-based drug-drug interactions with drugs approved by the U.S. Food and Drug Administration between 2013 and 2016. Drug Metab Dispos. 2018 Jun;46(6):835-845.
• [8] Comparison of the antifibrotic effects of the pan-histone deacetylase-inhibitor panobinostat versus the IPF-drug pirfenidone in fibroblasts from patients with idiopathic pulmonary fibrosis. PLoS One. 2018 Nov 27;13(11):e0207915. doi: 10.1371/journal.pone.0207915. eCollection 2018.
• [9] Human precision-cut liver slices as a model to test antifibrotic drugs in the early onset of liver fibrosis. Toxicol In Vitro. 2016 Sep;35:77-85. doi: 10.1016/j.tiv.2016.05.012. Epub 2016 May 26.
• [10] Targeting the myofibroblast genetic switch: inhibitors of myocardin-related transcription factor/serum response factor-regulated gene transcription prevent fibrosis in a murine model of skin injury. J Pharmacol Exp Ther. 2014 Jun;349(3):480-6. doi: 10.1124/jpet.114.213520. Epub 2014 Apr 4.
• [11] ClinicalTrials.gov (NCT01417156) Safety and PK Study of BIBF 1120 in Japanese Patients With IPF: Follow up Study From 1199.31(NCT01136174)