Details of the Drug Combination

General Information of Drug Combination (ID: DCF4Q9G)

• Drug Combination Name: Levonorgestrel + Mefenamic acid
• Indication: Uterine Hemorrhage; Status: Phase 1 [1]
• Component Drugs:
  Levonorgestrel (DM1DP7T): Small molecular drug
  Mefenamic acid (DMK7HFI): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Levonorgestrel

Disease Entry	ICD 11	Status	REF
Atypical endometrial hyperplasia	N.A.	Approved	[2]
Contraception	QA21	Approved	[3]
Hot flushes	GA30	Approved	[2]
Menorrhagia	GA20.50	Approved	[2]

Levonorgestrel Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Progesterone receptor (PGR)	TTUV8G9	PRGR_HUMAN	Binder	[7]

Levonorgestrel Interacts with 10 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[8]
Aldo-keto reductase family 1 member C3 (AKR1C3)	OTU2SXBA	AK1C3_HUMAN	Decreases Activity	[9]
Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B)	OTQ4W7MT	TR11B_HUMAN	Increases Expression	[10]
Tumor necrosis factor ligand superfamily member 11 (TNFSF11)	OTJEPKEQ	TNF11_HUMAN	Decreases Expression	[10]
Low-density lipoprotein receptor (LDLR)	OTH559LU	LDLR_HUMAN	Affects Expression	[11]
Lutropin subunit beta (LHB)	OT5GBOVJ	LSHB_HUMAN	Decreases Secretion	[12]
Sex hormone-binding globulin (SHBG)	OTPWU5IW	SHBG_HUMAN	Affects Binding	[13]
Prostate-specific antigen (KLK3)	OTFGSBFJ	KLK3_HUMAN	Increases Expression	[14]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[15]
Proliferation marker protein Ki-67 (MKI67)	OTA8N1QI	KI67_HUMAN	Decreases Expression	[15]

Indication(s) of Mefenamic acid

Disease Entry	ICD 11	Status	REF
Dysmenorrhea	GA34.3	Approved	[4]
Pain	MG30-MG3Z	Approved	[5]

Mefenamic acid Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Prostaglandin G/H synthase 2 (COX-2)	TTVKILB	PGH2_HUMAN	Inhibitor	[17]

Mefenamic acid Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[18]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[19]
Cytochrome P450 102A1 (cyp102)	DE4OGUF	CPXB_BACMB	Metabolism	[20]

Mefenamic acid Interacts with 28 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2C9 (CYP2C9)	OTGLBN29	CP2C9_HUMAN	Increases Glutathionylation	[19]
Solute carrier family 22 member 1 (SLC22A1)	OT7817I4	S22A1_HUMAN	Decreases Activity	[21]
Solute carrier family 22 member 6 (SLC22A6)	OTKRCBVM	S22A6_HUMAN	Decreases Activity	[21]
Organic anion transporter 7 (SLC22A9)	OTO4BJCC	S22A9_HUMAN	Decreases Activity	[21]
Solute carrier family 22 member 11 (SLC22A11)	OTAJLNJZ	S22AB_HUMAN	Decreases Activity	[21]
Solute carrier family 22 member 7 (SLC22A7)	OTKTNH1W	S22A7_HUMAN	Decreases Activity	[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]
Sulfotransferase 1A1 (SULT1A1)	OT0K7JIE	ST1A1_HUMAN	Decreases Activity	[23]
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Increases Activity	[24]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Decreases Secretion	[25]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[26]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Decreases Secretion	[25]
L-selectin (SELL)	OT6RAJZR	LYAM1_HUMAN	Decreases Expression	[27]
15-hydroxyprostaglandin dehydrogenase (HPGD)	OTYZI6JB	PGDH_HUMAN	Increases Expression	[28]
Cytochrome P450 4A11 (CYP4A11)	OTPU5J0S	CP4AB_HUMAN	Affects Activity	[29]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Decreases Activity	[30]
Major histocompatibility complex class I-related gene protein (MR1)	OTZU3XX7	HMR1_HUMAN	Affects Expression	[31]
Glutathione S-transferase A1 (GSTA1)	OTA7K5XA	GSTA1_HUMAN	Increases Glutathionylation	[19]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Increases Glutathionylation	[19]
Cytochrome P450 2C19 (CYP2C19)	OTFMJYYE	CP2CJ_HUMAN	Increases Hydroxylation	[19]
Glutathione S-transferase Mu 3 (GSTM3)	OTLA2WJT	GSTM3_HUMAN	Increases Glutathionylation	[19]
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Increases Glutathionylation	[19]
Glutathione S-transferase P (GSTP1)	OTLP0A0Y	GSTP1_HUMAN	Increases Glutathionylation	[19]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Glutathionylation	[19]
Glutathione S-transferase Mu 1 (GSTM1)	OTSBF2MO	GSTM1_HUMAN	Increases Glutathionylation	[19]
Glutathione S-transferase A2 (GSTA2)	OTW7UB1H	GSTA2_HUMAN	Increases Glutathionylation	[19]

References

• [1] ClinicalTrials.gov (NCT01295294) Management of Initial Bleeding/Spotting Associated With the Levonorgestrel-releasing Intrauterine System (MIRENA)
• [2] Levonorgestrel FDA Label
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• [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: 2593).
• [5] Mefenamic acid FDA Label
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