Details of the Drug Combination

General Information of Drug Combination (ID: DC1SVVF)

• Drug Combination Name: Duloxetine + Naproxen
• Indication: Back Pain, Low; Status: Phase 4 [1]
• Component Drugs:
  Duloxetine (DM9BI7M): Small molecular drug
  Naproxen (DMZ5RGV): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Duloxetine

Disease Entry	ICD 11	Status	REF
Depression	6A70-6A7Z	Approved	[2]
Major depressive disorder	6A70.3	Approved	[3]
Stress urinary incontinence	MF50.20	Approved	[3]
Traumatic brain injury	NA07.Z	Approved	[3]

Duloxetine Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Norepinephrine transporter (NET)	TTAWNKZ	SC6A2_HUMAN	Inhibitor	[8]
Serotonin transporter (SERT)	TT3ROYC	SC6A4_HUMAN	Inhibitor	[8]

Duloxetine Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[9]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[9]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[9]

Indication(s) of Naproxen

Disease Entry	ICD 11	Status	REF
Bursitis	N.A.	Approved	[4]
Dysmenorrhea	GA34.3	Approved	[4]
Fever	MG26	Approved	[4]
Gout	FA25	Approved	[4]
Headache	8A80-8A84	Approved	[4]
Migraine disorder	N.A.	Approved	[4]
Osteoarthritis	FA00-FA05	Approved	[5]
Pain	MG30-MG3Z	Phase 2	[6]
Endometriosis	GA10	Investigative	[7]

Naproxen Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Prostaglandin G/H synthase 1 (COX-1)	TT8NGED	PGH1_HUMAN	Inhibitor	[14]
Prostaglandin G/H synthase 2 (COX-2)	TTVKILB	PGH2_HUMAN	Inhibitor	[14]

Naproxen Interacts with 9 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[15]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[16]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[15]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[17]
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Metabolism	[18]
UDP-glucuronosyltransferase 1A3 (UGT1A3)	DEF2WXN	UD13_HUMAN	Metabolism	[19]
UDP-glucuronosyltransferase 1A9 (UGT1A9)	DE85D2P	UD19_HUMAN	Metabolism	[19]
UDP-glucuronosyltransferase 1A6 (UGT1A6)	DESD26P	UD16_HUMAN	Metabolism	[19]
UDP-glucuronosyltransferase 1A10 (UGT1A10)	DEL5N6Y	UD110_HUMAN	Metabolism	[19]

Naproxen Interacts with 16 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Solute carrier family 22 member 2 (SLC22A2)	OTGFK1AL	S22A2_HUMAN	Decreases Activity	[20]
Solute carrier family 22 member 6 (SLC22A6)	OTKRCBVM	S22A6_HUMAN	Decreases Activity	[20]
Organic anion transporter 7 (SLC22A9)	OTO4BJCC	S22A9_HUMAN	Decreases Activity	[20]
Solute carrier family 22 member 11 (SLC22A11)	OTAJLNJZ	S22AB_HUMAN	Decreases Activity	[20]
Solute carrier family 22 member 7 (SLC22A7)	OTKTNH1W	S22A7_HUMAN	Decreases Activity	[20]
Tumor necrosis factor receptor superfamily member 16 (NGFR)	OTPKSM49	TNR16_HUMAN	Increases Expression	[21]
Aldo-keto reductase family 1 member C3 (AKR1C3)	OTU2SXBA	AK1C3_HUMAN	Decreases Activity	[22]
Aldo-keto reductase family 1 member C2 (AKR1C2)	OTQ2XMO3	AK1C2_HUMAN	Decreases Activity	[22]
Aldo-keto reductase family 1 member C1 (AKR1C1)	OTQKR4CM	AK1C1_HUMAN	Decreases Activity	[22]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[23]
Renin (REN)	OT52GZR2	RENI_HUMAN	Decreases Activity	[24]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[25]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Affects Expression	[26]
HLA class II histocompatibility antigen, DM beta chain (HLA-DMB)	OT17HGXJ	DMB_HUMAN	Affects Expression	[27]
Cytochrome P450 4A11 (CYP4A11)	OTPU5J0S	CP4AB_HUMAN	Affects Activity	[28]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Affects Activity	[26]

References

• [1] ClinicalTrials.gov (NCT05851976) Duloxetine for LBP
• [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: 202).
• [3] Duloxetine FDA Label
• [4] Naproxen FDA Label
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [6] 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: 5230).
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• [21] The aryl propionic acid R-flurbiprofen selectively induces p75NTR-dependent decreased survival of prostate tumor cells. Cancer Res. 2007 Apr 1;67(7):3254-62.
• [22] Type 5 17beta-hydroxysteroid dehydrogenase/prostaglandin F synthase (AKR1C3): role in breast cancer and inhibition by non-steroidal anti-inflammatory drug analogs. Chem Biol Interact. 2009 Mar 16;178(1-3):221-7.
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• [24] Effects of sulindac and naproxen on prostaglandin excretion in patients with impaired renal function and rheumatoid arthritis. Am J Med. 1990 Sep;89(3):313-21. doi: 10.1016/0002-9343(90)90344-d.
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