Details of the Drug Combination

General Information of Drug Combination (ID: DCSVZKV)

• Drug Combination Name: Nevirapine + Atazanavir
• Indication: HIV Infections; Status: Phase 4 [1]
• Component Drugs:
  Nevirapine (DM6HX9B): Small molecular drug
  Atazanavir (DMSYRBX): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Nevirapine

Disease Entry	ICD 11	Status	REF
Human immunodeficiency virus infection	1C62	Approved	[2]

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	[6]

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	[7]

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	[8]
Cytochrome P450 2A6 (CYP2A6)	DEJVYAZ	CP2A6_HUMAN	Metabolism	[9]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[8]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[9]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[10]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[11]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[12]

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	[13]
Sterol carrier protein 2 (SCP2)	OTPAFCPQ	SCP2_HUMAN	Increases Expression	[14]
MHC class II transactivator (CIITA)	OTRJNZFO	C2TA_HUMAN	Increases Expression	[14]
Protein NLRC5 (NLRC5)	OTY8X6MC	NLRC5_HUMAN	Increases Expression	[14]
Proepiregulin (EREG)	OTRM4NQY	EREG_HUMAN	Increases Expression	[15]
Epidermal growth factor receptor (EGFR)	OTAPLO1S	EGFR_HUMAN	Decreases Expression	[4]
Pro-epidermal growth factor (EGF)	OTANRJ0L	EGF_HUMAN	Decreases Expression	[4]
Thyroglobulin (TG)	OT3ELHIJ	THYG_HUMAN	Increases Expression	[16]
Interferon gamma (IFNG)	OTXG9JM7	IFNG_HUMAN	Increases Expression	[17]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Increases Expression	[15]
Apolipoprotein A-I (APOA1)	OT5THARI	APOA1_HUMAN	Increases Expression	[18]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[19]
Phosphatidylcholine-sterol acyltransferase (LCAT)	OTRLMLK0	LCAT_HUMAN	Increases Expression	[18]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Decreases Secretion	[20]
Keratin, type I cytoskeletal 18 (KRT18)	OTVLQFIP	K1C18_HUMAN	Increases Expression	[4]
Lipoprotein lipase (LPL)	OTTW0267	LIPL_HUMAN	Increases Expression	[20]
Thyroid peroxidase (TPO)	OTJJLL20	PERT_HUMAN	Increases Expression	[16]
Prostate-specific antigen (KLK3)	OTFGSBFJ	KLK3_HUMAN	Increases Expression	[4]
Hepatocyte growth factor receptor (MET)	OT7K55MU	MET_HUMAN	Increases Expression	[15]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[15]
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Increases Expression	[4]
Cholesteryl ester transfer protein (CETP)	OTAGPPOE	CETP_HUMAN	Increases Expression	[18]
Hepatocyte growth factor (HGF)	OTGHUA23	HGF_HUMAN	Decreases Secretion	[20]
Thyrotropin receptor (TSHR)	OT0BC8LB	TSHR_HUMAN	Increases Expression	[16]
Bone morphogenetic protein 6 (BMP6)	OT9WN536	BMP6_HUMAN	Increases Expression	[15]
Sterol regulatory element-binding protein 1 (SREBF1)	OTWBRPAI	SRBP1_HUMAN	Increases Expression	[20]
Peroxisome proliferator-activated receptor gamma (PPARG)	OTHMARHO	PPARG_HUMAN	Increases Expression	[20]
Leptin (LEP)	OT5Q7ODW	LEP_HUMAN	Increases Expression	[20]
CCAAT/enhancer-binding protein alpha (CEBPA)	OTOM9OE4	CEBPA_HUMAN	Increases Expression	[20]
Tumor necrosis factor-inducible gene 6 protein (TNFAIP6)	OT1SLUZH	TSG6_HUMAN	Increases Expression	[15]
Interleukin-24 (IL24)	OT4VUWH1	IL24_HUMAN	Increases Expression	[15]
Adiponectin (ADIPOQ)	OTNX23LE	ADIPO_HUMAN	Increases Expression	[20]
PTB-containing, cubilin and LRP1-interacting protein (PID1)	OT5YJ7FI	PCLI1_HUMAN	Increases Expression	[15]
Cystine/glutamate transporter (SLC7A11)	OTKJ6PXW	XCT_HUMAN	Increases Expression	[15]
Glutathione S-transferase A1 (GSTA1)	OTA7K5XA	GSTA1_HUMAN	Increases Glutathionylation	[21]
Glutathione S-transferase A3 (GSTA3)	OTJ3REE3	GSTA3_HUMAN	Increases Glutathionylation	[21]
Glutathione S-transferase P (GSTP1)	OTLP0A0Y	GSTP1_HUMAN	Increases Glutathionylation	[21]
Glutathione S-transferase Mu 1 (GSTM1)	OTSBF2MO	GSTM1_HUMAN	Increases Glutathionylation	[21]

Indication(s) of Atazanavir

Disease Entry	ICD 11	Status	REF
Human immunodeficiency virus infection	1C62	Approved	[3]

Atazanavir Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human immunodeficiency virus Protease (HIV PR)	TT5FNQT	POL_HV1B1	Modulator	[24]

Atazanavir Interacts with 5 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[25]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[26]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[25]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[25]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[27]

Atazanavir Interacts with 47 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Decreases Expression	[23]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[28]
ATP-binding cassette sub-family C member 3 (ABCC3)	OTC3IJV4	MRP3_HUMAN	Decreases Expression	[23]
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Decreases Expression	[23]
Phosphatidylinositol 3-kinase C2 domain-containing subunit gamma (PIK3C2G)	OTW3LY1C	P3C2G_HUMAN	Decreases Expression	[23]
Aflatoxin B1 aldehyde reductase member 3 (AKR7A3)	OTW3GO4Y	ARK73_HUMAN	Decreases Expression	[23]
Ubiquitin-like modifier-activating enzyme ATG7 (ATG7)	OTVT4YA1	ATG7_HUMAN	Increases Expression	[23]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[19]
Catalase (CAT)	OTHEBX9R	CATA_HUMAN	Decreases Expression	[23]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Increases Expression	[23]
Plasminogen activator inhibitor 1 (SERPINE1)	OTT0MPQ3	PAI1_HUMAN	Increases Expression	[23]
Intercellular adhesion molecule 1 (ICAM1)	OTTOIX77	ICAM1_HUMAN	Increases Expression	[29]
Epoxide hydrolase 1 (EPHX1)	OTBKWQER	HYEP_HUMAN	Decreases Expression	[23]
Glutathione S-transferase A1 (GSTA1)	OTA7K5XA	GSTA1_HUMAN	Decreases Expression	[23]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Increases Expression	[29]
Macrophage colony-stimulating factor 1 (CSF1)	OT68M7RD	CSF1_HUMAN	Increases Expression	[23]
C-C motif chemokine 3 (CCL3)	OTW2H3ND	CCL3_HUMAN	Increases Expression	[30]
Endoplasmic reticulum chaperone BiP (HSPA5)	OTFUIRAO	BIP_HUMAN	Decreases Expression	[23]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Expression	[30]
Fos-related antigen 1 (FOSL1)	OT9YTYMB	FOSL1_HUMAN	Increases Expression	[23]
Glutathione peroxidase 2 (GPX2)	OTXI2NTI	GPX2_HUMAN	Decreases Expression	[23]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4)	OTRFV19J	ATF4_HUMAN	Increases Expression	[23]
Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6)	OTAFHAVI	ATF6A_HUMAN	Increases Expression	[23]
Cytochrome P450 2B6 (CYP2B6)	OTOYO4S7	CP2B6_HUMAN	Decreases Expression	[23]
Cytochrome P450 7A1 (CYP7A1)	OT8Z5KLD	CP7A1_HUMAN	Decreases Expression	[23]
Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1)	OT5BZ1J9	P85A_HUMAN	Decreases Expression	[23]
DNA damage-inducible transcript 3 protein (DDIT3)	OTI8YKKE	DDIT3_HUMAN	Increases Expression	[23]
Dual specificity mitogen-activated protein kinase kinase 6 (MAP2K6)	OTK13JKC	MP2K6_HUMAN	Decreases Expression	[23]
Flavin-containing monooxygenase 1 (FMO1)	OTTHSQKP	FMO1_HUMAN	Decreases Expression	[23]
Sulfotransferase 2A1 (SULT2A1)	OT0ISKQ4	ST2A1_HUMAN	Decreases Expression	[23]
Peptidyl-prolyl cis-trans isomerase FKBP5 (FKBP5)	OT404F9K	FKBP5_HUMAN	Decreases Expression	[23]
Sequestosome-1 (SQSTM1)	OTGY5D5J	SQSTM_HUMAN	Increases Expression	[23]
Hepatic sodium/bile acid cotransporter (SLC10A1)	OTUJVMCL	NTCP_HUMAN	Decreases Expression	[23]
Nuclear receptor subfamily 1 group I member 3 (NR1I3)	OTS3SGH7	NR1I3_HUMAN	Decreases Expression	[23]
MAP kinase-activated protein kinase 3 (MAPKAPK3)	OT7IWJNI	MAPK3_HUMAN	Increases Expression	[23]
Glutathione S-transferase A3 (GSTA3)	OTJ3REE3	GSTA3_HUMAN	Decreases Expression	[23]
DnaJ homolog subfamily C member 10 (DNAJC10)	OTD2EG0R	DJC10_HUMAN	Increases Expression	[23]
Mixed lineage kinase domain-like protein (MLKL)	OTDSLC81	MLKL_HUMAN	Increases Expression	[23]
DnaJ homolog subfamily C member 9 (DNAJC9)	OTDBQBNZ	DNJC9_HUMAN	Increases Expression	[23]
ATP-binding cassette sub-family C member 2 (ABCC2)	OTJSIGV5	MRP2_HUMAN	Decreases Expression	[23]
Bile acid receptor (NR1H4)	OTWZLPTB	NR1H4_HUMAN	Decreases Expression	[23]
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B)	OTUYHB84	MLP3B_HUMAN	Increases Expression	[23]
Ubiquitin carboxyl-terminal hydrolase CYLD (CYLD)	OT37FKH0	CYLD_HUMAN	Increases Expression	[23]
Transcription factor MafF (MAFF)	OT9B7MX0	MAFF_HUMAN	Increases Expression	[23]
Endophilin-B1 (SH3GLB1)	OTAZ5OP8	SHLB1_HUMAN	Increases Expression	[23]
Solute carrier organic anion transporter family member 1B1 (SLCO1B1)	OTNEN8QK	SO1B1_HUMAN	Decreases Expression	[23]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Transport	[31]

References

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• [21] 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.
• [22] Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for UGT1A1 and Atazanavir Prescribing. Clin Pharmacol Ther. 2016 Apr;99(4):363-9. doi: 10.1002/cpt.269. Epub 2015 Nov 9.
• [23] Robustness testing and optimization of an adverse outcome pathway on cholestatic liver injury. Arch Toxicol. 2020 Apr;94(4):1151-1172. doi: 10.1007/s00204-020-02691-9. Epub 2020 Mar 10.
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