Details of the Drug Combination

General Information of Drug Combination (ID: DCZO5AK)

• Drug Combination Name: Levonorgestrel + Nevirapine
• Indication: HIV; Status: Phase 1 [1]
• Component Drugs:
  Levonorgestrel (DM1DP7T): Small molecular drug
  Nevirapine (DM6HX9B): 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	[6]

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	[7]
Aldo-keto reductase family 1 member C3 (AKR1C3)	OTU2SXBA	AK1C3_HUMAN	Decreases Activity	[8]
Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B)	OTQ4W7MT	TR11B_HUMAN	Increases Expression	[9]
Tumor necrosis factor ligand superfamily member 11 (TNFSF11)	OTJEPKEQ	TNF11_HUMAN	Decreases Expression	[9]
Low-density lipoprotein receptor (LDLR)	OTH559LU	LDLR_HUMAN	Affects Expression	[10]
Lutropin subunit beta (LHB)	OT5GBOVJ	LSHB_HUMAN	Decreases Secretion	[11]
Sex hormone-binding globulin (SHBG)	OTPWU5IW	SHBG_HUMAN	Affects Binding	[12]
Prostate-specific antigen (KLK3)	OTFGSBFJ	KLK3_HUMAN	Increases Expression	[13]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[14]
Proliferation marker protein Ki-67 (MKI67)	OTA8N1QI	KI67_HUMAN	Decreases Expression	[14]

Indication(s) of Nevirapine

Disease Entry	ICD 11	Status	REF
Human immunodeficiency virus infection	1C62	Approved	[4]

Nevirapine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human immunodeficiency virus Reverse transcriptase (HIV RT)	TT84ETX	POL_HV1B1	Modulator	[17]

Nevirapine Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[18]

Nevirapine Interacts with 7 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[19]
Cytochrome P450 2A6 (CYP2A6)	DEJVYAZ	CP2A6_HUMAN	Metabolism	[20]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[19]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[20]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[21]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[22]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[23]

Nevirapine Interacts with 38 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Affects Binding	[24]
Sterol carrier protein 2 (SCP2)	OTPAFCPQ	SCP2_HUMAN	Increases Expression	[25]
MHC class II transactivator (CIITA)	OTRJNZFO	C2TA_HUMAN	Increases Expression	[25]
Protein NLRC5 (NLRC5)	OTY8X6MC	NLRC5_HUMAN	Increases Expression	[25]
Proepiregulin (EREG)	OTRM4NQY	EREG_HUMAN	Increases Expression	[26]
Epidermal growth factor receptor (EGFR)	OTAPLO1S	EGFR_HUMAN	Decreases Expression	[15]
Pro-epidermal growth factor (EGF)	OTANRJ0L	EGF_HUMAN	Decreases Expression	[15]
Thyroglobulin (TG)	OT3ELHIJ	THYG_HUMAN	Increases Expression	[27]
Interferon gamma (IFNG)	OTXG9JM7	IFNG_HUMAN	Increases Expression	[28]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Increases Expression	[26]
Apolipoprotein A-I (APOA1)	OT5THARI	APOA1_HUMAN	Increases Expression	[29]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[30]
Phosphatidylcholine-sterol acyltransferase (LCAT)	OTRLMLK0	LCAT_HUMAN	Increases Expression	[29]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Decreases Secretion	[31]
Keratin, type I cytoskeletal 18 (KRT18)	OTVLQFIP	K1C18_HUMAN	Increases Expression	[15]
Lipoprotein lipase (LPL)	OTTW0267	LIPL_HUMAN	Increases Expression	[31]
Thyroid peroxidase (TPO)	OTJJLL20	PERT_HUMAN	Increases Expression	[27]
Prostate-specific antigen (KLK3)	OTFGSBFJ	KLK3_HUMAN	Increases Expression	[15]
Hepatocyte growth factor receptor (MET)	OT7K55MU	MET_HUMAN	Increases Expression	[26]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[26]
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Increases Expression	[15]
Cholesteryl ester transfer protein (CETP)	OTAGPPOE	CETP_HUMAN	Increases Expression	[29]
Hepatocyte growth factor (HGF)	OTGHUA23	HGF_HUMAN	Decreases Secretion	[31]
Thyrotropin receptor (TSHR)	OT0BC8LB	TSHR_HUMAN	Increases Expression	[27]
Bone morphogenetic protein 6 (BMP6)	OT9WN536	BMP6_HUMAN	Increases Expression	[26]
Sterol regulatory element-binding protein 1 (SREBF1)	OTWBRPAI	SRBP1_HUMAN	Increases Expression	[31]
Peroxisome proliferator-activated receptor gamma (PPARG)	OTHMARHO	PPARG_HUMAN	Increases Expression	[31]
Leptin (LEP)	OT5Q7ODW	LEP_HUMAN	Increases Expression	[31]
CCAAT/enhancer-binding protein alpha (CEBPA)	OTOM9OE4	CEBPA_HUMAN	Increases Expression	[31]
Tumor necrosis factor-inducible gene 6 protein (TNFAIP6)	OT1SLUZH	TSG6_HUMAN	Increases Expression	[26]
Interleukin-24 (IL24)	OT4VUWH1	IL24_HUMAN	Increases Expression	[26]
Adiponectin (ADIPOQ)	OTNX23LE	ADIPO_HUMAN	Increases Expression	[31]
PTB-containing, cubilin and LRP1-interacting protein (PID1)	OT5YJ7FI	PCLI1_HUMAN	Increases Expression	[26]
Cystine/glutamate transporter (SLC7A11)	OTKJ6PXW	XCT_HUMAN	Increases Expression	[26]
Glutathione S-transferase A1 (GSTA1)	OTA7K5XA	GSTA1_HUMAN	Increases Glutathionylation	[32]
Glutathione S-transferase A3 (GSTA3)	OTJ3REE3	GSTA3_HUMAN	Increases Glutathionylation	[32]
Glutathione S-transferase P (GSTP1)	OTLP0A0Y	GSTP1_HUMAN	Increases Glutathionylation	[32]
Glutathione S-transferase Mu 1 (GSTM1)	OTSBF2MO	GSTM1_HUMAN	Increases Glutathionylation	[32]

References

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• [2] Levonorgestrel FDA Label
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• [21] Helices F-G are important for the substrate specificities of CYP3A7. Drug Metab Dispos. 2007 Mar;35(3):484-92.
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• [32] Different Reactive Metabolites of Nevirapine Require Distinct Glutathione S-Transferase Isoforms for Bioinactivation. Chem Res Toxicol. 2016 Dec 19;29(12):2136-2144. doi: 10.1021/acs.chemrestox.6b00250. Epub 2016 Nov 28.