Details of the Drug Combination

General Information of Drug Combination (ID: DCOV22X)

• Drug Combination Name: Fenofibrate + Rosuvastatin
• Indication: Dyslipidemia, Renal Insufficiency; Status: Phase 1 [1]
• Component Drugs:
  Fenofibrate (DMFKXDY): Small molecular drug
  Rosuvastatin (DMMIQ7G): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Fenofibrate

Disease Entry	ICD 11	Status	REF
Coronary atherosclerosis	N.A.	Approved	[2]
High cholesterol level	5C80.0	Approved	[3]
Hypercholesterolaemia	5C80.0	Approved	[2]
Hyperlipidemia	5C80.Z	Approved	[2]
Hyperlipidemia, familial combined, LPL related	N.A.	Approved	[2]
Hypertriglyceridemia	5C80.1	Approved	[2]
Obesity	5B81	Approved	[2]

Fenofibrate Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Peroxisome proliferator-activated receptor alpha (PPARA)	TTJ584C	PPARA_HUMAN	Agonist	[10]

Fenofibrate Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[11]
UDP-glucuronosyltransferase 1A9 (UGT1A9)	DE85D2P	UD19_HUMAN	Metabolism	[12]

Fenofibrate Interacts with 240 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
C-reactive protein (CRP)	OT0RFT8F	CRP_HUMAN	Decreases Expression	[13]
Serum paraoxonase/arylesterase 1 (PON1)	OTD0Z2XO	PON1_HUMAN	Increases Expression	[13]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[14]
S-adenosylmethionine synthase isoform type-2 (MAT2A)	OTFJMIQR	METK2_HUMAN	Decreases Expression	[14]
Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2)	OTJ8LX4N	PCKGM_HUMAN	Increases Expression	[14]
Acyl-CoA (FADS1)	OTUYOYHX	FADS1_HUMAN	Increases Expression	[15]
Aldo-keto reductase family 1 member B10 (AKR1B10)	OTOA4HTH	AK1BA_HUMAN	Decreases Activity	[16]
Phosphatidylcholine translocator ABCB4 (ABCB4)	OTE6PY83	MDR3_HUMAN	Increases Expression	[17]
Cytochrome P450 3A7 (CYP3A7)	OTTCDHHM	CP3A7_HUMAN	Increases Expression	[17]
Nitric oxide synthase 3 (NOS3)	OTLDT7NR	NOS3_HUMAN	Increases Activity	[18]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[19]
Isocitrate dehydrogenase subunit beta, mitochondrial (IDH3B)	OTR89YF5	IDH3B_HUMAN	Increases Expression	[7]
Apolipoprotein C-III (APOC3)	OTW3520C	APOC3_HUMAN	Decreases Expression	[7]
Lipoprotein lipase (LPL)	OTTW0267	LIPL_HUMAN	Increases Expression	[7]
Fatty acid-binding protein, liver (FABP1)	OTR34ETM	FABPL_HUMAN	Increases Expression	[7]
3-ketoacyl-CoA thiolase, peroxisomal (ACAA1)	OTVKRET0	THIK_HUMAN	Increases Expression	[7]
Medium-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADM)	OTA4P0FC	ACADM_HUMAN	Increases Expression	[7]
Succinate dehydrogenase iron-sulfur subunit, mitochondrial (SDHB)	OTRE1M1T	SDHB_HUMAN	Increases Expression	[7]
Acetyl-CoA acetyltransferase, mitochondrial (ACAT1)	OTJC60Q7	THIL_HUMAN	Increases Expression	[7]
Enoyl-CoA hydratase, mitochondrial (ECHS1)	OTS0593S	ECHM_HUMAN	Increases Expression	[7]
Long-chain-fatty-acid--CoA ligase 1 (ACSL1)	OTB06ESI	ACSL1_HUMAN	Increases Expression	[7]
Phosphoglucomutase-1 (PGM1)	OT3VM4JX	PGM1_HUMAN	Increases Expression	[7]
Very long-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADVL)	OT50L4XB	ACADV_HUMAN	Increases Expression	[7]
Succinate--CoA ligase subunit alpha, mitochondrial (SUCLG1)	OTDCSPXH	SUCA_HUMAN	Increases Expression	[7]
Trifunctional enzyme subunit beta, mitochondrial (HADHB)	OT4Y1I62	ECHB_HUMAN	Increases Expression	[7]
Methylmalonate-semialdehyde/malonate-semialdehyde dehydrogenase , mitochondrial (ALDH6A1)	OT8LCZCT	MMSA_HUMAN	Increases Expression	[7]
Acetyl-CoA carboxylase 1 (ACACA)	OT5CQPZY	ACACA_HUMAN	Decreases Expression	[7]
Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1)	OTM0A0DY	ACOX1_HUMAN	Increases Expression	[7]
Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (HADH)	OTJDOL20	HCDH_HUMAN	Increases Expression	[7]
Long-chain fatty acid transport protein 4 (SLC27A4)	OTWT4HAF	S27A4_HUMAN	Increases Expression	[7]
Aconitate hydratase, mitochondrial (ACO2)	OTF2UVNV	ACON_HUMAN	Increases Expression	[7]
Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B)	OTQ4W7MT	TR11B_HUMAN	Decreases Expression	[8]
CCN family member 1 (CCN1)	OTKJBEMD	CCN1_HUMAN	Decreases Expression	[8]
Krueppel-like factor 11 (KLF11)	OTKVQDJD	KLF11_HUMAN	Increases Expression	[8]
Long-chain fatty acid transport protein 2 (SLC27A2)	OT7JEG5F	S27A2_HUMAN	Increases Expression	[8]
Transcription intermediary factor 1-alpha (TRIM24)	OTA45FTS	TIF1A_HUMAN	Increases Expression	[8]
Insulin-induced gene 1 protein (INSIG1)	OTZF5X1D	INSI1_HUMAN	Decreases Expression	[8]
Interleukin-1 receptor-associated kinase-like 2 (IRAK2)	OT6Y1QZN	IRAK2_HUMAN	Increases Expression	[8]
Proline dehydrogenase 1, mitochondrial (PRODH)	OT7SQ1C7	PROD_HUMAN	Decreases Expression	[8]
Aquaporin-9 (AQP9)	OTLGH5ZY	AQP9_HUMAN	Decreases Expression	[8]
LYR motif-containing protein 1 (LYRM1)	OTV3AJDJ	LYRM1_HUMAN	Increases Expression	[8]
Mitochondrial carnitine/acylcarnitine carrier protein (SLC25A20)	OT6CLFXB	MCAT_HUMAN	Increases Expression	[8]
Perilipin-1 (PLIN1)	OT3OAAZ4	PLIN1_HUMAN	Increases Expression	[8]
Peroxisomal membrane protein 11A (PEX11A)	OT8MJ9CJ	PX11A_HUMAN	Increases Expression	[8]
Tumor necrosis factor receptor superfamily member 21 (TNFRSF21)	OT3EDGXO	TNR21_HUMAN	Increases Expression	[8]
2-amino-3-ketobutyrate coenzyme A ligase, mitochondrial (GCAT)	OT6WZPWV	KBL_HUMAN	Decreases Expression	[8]
Alcohol dehydrogenase 1C (ADH1C)	OTO1DV7F	ADH1G_HUMAN	Decreases Expression	[8]
Alkaline phosphatase, tissue-nonspecific isozyme (ALPL)	OTG7J4BP	PPBT_HUMAN	Decreases Expression	[8]
L-lactate dehydrogenase B chain (LDHB)	OT9B1CT3	LDHB_HUMAN	Increases Expression	[8]
Galactose-1-phosphate uridylyltransferase (GALT)	OTCATU66	GALT_HUMAN	Increases Expression	[8]
All-trans-retinol dehydrogenase ADH4 (ADH4)	OTKDKKNG	ADH4_HUMAN	Decreases Expression	[8]
Monocyte differentiation antigen CD14 (CD14)	OT83GJ47	CD14_HUMAN	Increases Expression	[8]
Cytochrome P450 2C8 (CYP2C8)	OTHCWT42	CP2C8_HUMAN	Increases Expression	[8]
Electron transfer flavoprotein subunit alpha, mitochondrial (ETFA)	OTXX61VZ	ETFA_HUMAN	Increases Expression	[8]
NADPH--cytochrome P450 reductase (POR)	OTVIDOCH	NCPR_HUMAN	Increases Expression	[8]
Platelet glycoprotein 4 (CD36)	OT5CZWKY	CD36_HUMAN	Increases Expression	[8]
Fumarylacetoacetase (FAH)	OTGZA1YR	FAAA_HUMAN	Increases Expression	[8]
Arylacetamide deacetylase (AADAC)	OT8VACT2	AAAD_HUMAN	Increases Expression	[8]
Plasma membrane calcium-transporting ATPase 4 (ATP2B4)	OTMWFDAC	AT2B4_HUMAN	Increases Expression	[8]
Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2)	OTIN6G20	CPT2_HUMAN	Increases Expression	[8]
11-beta-hydroxysteroid dehydrogenase 1 (HSD11B1)	OTO7FJA9	DHI1_HUMAN	Increases Expression	[8]
Pyruvate kinase PKLR (PKLR)	OTTTM1QI	KPYR_HUMAN	Decreases Expression	[8]
Glycerol kinase (GK)	OTK2YRA0	GLPK_HUMAN	Increases Expression	[8]
Cytochrome P450 2C19 (CYP2C19)	OTFMJYYE	CP2CJ_HUMAN	Increases Expression	[8]
Phosphoenolpyruvate carboxykinase, cytosolic (PCK1)	OTNWEJ5Y	PCKGC_HUMAN	Increases Expression	[8]
Glucose-6-phosphatase catalytic subunit 1 (G6PC1)	OTJ6FM9F	G6PC1_HUMAN	Decreases Expression	[8]
Trifunctional enzyme subunit alpha, mitochondrial (HADHA)	OTO557N2	ECHA_HUMAN	Increases Expression	[8]
3-ketoacyl-CoA thiolase, mitochondrial (ACAA2)	OTGLVWOP	THIM_HUMAN	Increases Expression	[8]
Tryptophan 2,3-dioxygenase (TDO2)	OTV5HKJ4	T23O_HUMAN	Increases Expression	[8]
Flavin-containing monooxygenase 5 (FMO5)	OTTILF8T	FMO5_HUMAN	Decreases Expression	[8]
Peroxisomal multifunctional enzyme type 2 (HSD17B4)	OT8733D7	DHB4_HUMAN	Increases Expression	[8]
Hydroxymethylglutaryl-CoA synthase, mitochondrial (HMGCS2)	OTC3RUN9	HMCS2_HUMAN	Increases Expression	[8]
Cytochrome P450 4A11 (CYP4A11)	OTPU5J0S	CP4AB_HUMAN	Increases Expression	[8]
Tyrosine-protein kinase Mer (MERTK)	OTWBRAJ6	MERTK_HUMAN	Increases Expression	[8]
Krueppel-like factor 10 (KLF10)	OT4F4UGS	KLF10_HUMAN	Increases Expression	[8]
Ectonucleotide pyrophosphatase/phosphodiesterase family member 2 (ENPP2)	OTTUU92F	ENPP2_HUMAN	Decreases Expression	[8]
Glycine N-methyltransferase (GNMT)	OT0O2OQO	GNMT_HUMAN	Decreases Expression	[8]
Metabotropic glutamate receptor 3 (GRM3)	OTJFGE9S	GRM3_HUMAN	Increases Expression	[8]
Hepatic sodium/bile acid cotransporter (SLC10A1)	OTUJVMCL	NTCP_HUMAN	Decreases Expression	[8]
Monocyte to macrophage differentiation factor (MMD)	OTB5I4OC	PAQRB_HUMAN	Increases Expression	[8]
2'-5'-oligoadenylate synthase-like protein (OASL)	OTZ05YRP	OASL_HUMAN	Increases Expression	[8]
Myosin light chain kinase, smooth muscle (MYLK)	OT78QB4A	MYLK_HUMAN	Decreases Expression	[8]
Electron transfer flavoprotein-ubiquinone oxidoreductase, mitochondrial (ETFDH)	OTOSKSFH	ETFD_HUMAN	Increases Expression	[8]
Laminin subunit alpha-4 (LAMA4)	OTHI7TA0	LAMA4_HUMAN	Increases Expression	[8]
kinase isozyme 4, mitochondrial (PDK4)	OTCMHMBZ	PDK4_HUMAN	Increases Expression	[8]
Phospholipase A1 member A (PLA1A)	OT2IXYNX	PLA1A_HUMAN	Increases Expression	[8]
Protein LBH (LBH)	OT87AT1X	LBH_HUMAN	Increases Expression	[8]
NEDD4-binding protein 2-like 1 (N4BP2L1)	OTEGV3GO	N42L1_HUMAN	Increases Expression	[8]
Cytochrome P450 4A22 (CYP4A22)	OTHO7KC4	CP4AM_HUMAN	Increases Expression	[8]
Protein FAM222A (FAM222A)	OTRD9AUH	F222A_HUMAN	Increases Expression	[8]
PI-PLC X domain-containing protein 3 (PLCXD3)	OTJNSWMU	PLCX3_HUMAN	Decreases Expression	[8]
Cyclic AMP-responsive element-binding protein 3-like protein 3 (CREB3L3)	OTDMU3GP	CR3L3_HUMAN	Increases Expression	[8]
Lysophospholipid acyltransferase 5 (LPCAT3)	OTWI96P4	MBOA5_HUMAN	Increases Expression	[8]
Solute carrier family 25 member 34 (SLC25A34)	OTY1YFLG	S2534_HUMAN	Increases Expression	[8]
Leucine-rich repeat-containing protein 31 (LRRC31)	OT7VCU13	LRC31_HUMAN	Increases Expression	[8]
Lysophosphatidylcholine acyltransferase 2 (LPCAT2)	OT6NTBAA	PCAT2_HUMAN	Increases Expression	[8]
Monocarboxylate transporter 13 (SLC16A13)	OTAJ5CPB	MOT13_HUMAN	Increases Expression	[8]
Target of Nesh-SH3 (ABI3BP)	OTW8DN50	TARSH_HUMAN	Decreases Expression	[8]
Alpha-protein kinase 2 (ALPK2)	OTWZZDQ9	ALPK2_HUMAN	Increases Expression	[8]
4-hydroxy-2-oxoglutarate aldolase, mitochondrial (HOGA1)	OT7XETW4	HOGA1_HUMAN	Decreases Expression	[8]
Sphingosine-1-phosphate transporter SPNS2 (SPNS2)	OTPODAPU	SPNS2_HUMAN	Increases Expression	[8]
Cyclin-dependent kinase 20 (CDK20)	OTOLNN68	CDK20_HUMAN	Increases Expression	[8]
Cytochrome P450 4X1 (CYP4X1)	OTMTEUNE	CP4X1_HUMAN	Increases Expression	[8]
Uncharacterized protein FAM241A (FAM241A)	OTC12ETA	F241A_HUMAN	Increases Expression	[8]
Sodium-dependent lysophosphatidylcholine symporter 1 (MFSD2A)	OTVG1VG0	NLS1_HUMAN	Decreases Expression	[8]
Pantothenate kinase 1 (PANK1)	OT2CZVRT	PANK1_HUMAN	Increases Expression	[8]
Thyroid hormone-inducible hepatic protein (THRSP)	OTKYE01L	THRSP_HUMAN	Decreases Expression	[8]
Interferon regulatory factor 7 (IRF7)	OTC1A2PQ	IRF7_HUMAN	Increases Expression	[8]
Bcl-2-modifying factor (BMF)	OT90NSLI	BMF_HUMAN	Increases Expression	[8]
Membrane-spanning 4-domains subfamily A member 10 (MS4A10)	OTH3LAUX	M4A10_HUMAN	Decreases Expression	[8]
Perilipin-2 (PLIN2)	OTRXJ9UN	PLIN2_HUMAN	Increases Expression	[8]
C-C motif chemokine 13 (CCL13)	OTNX0JD0	CCL13_HUMAN	Increases Expression	[8]
Ion channel TACAN (TMEM120A)	OTBS3YWY	TACAN_HUMAN	Decreases Expression	[8]
Angiopoietin-related protein 4 (ANGPTL4)	OTQL5SPX	ANGL4_HUMAN	Increases Expression	[8]
Alanine--glyoxylate aminotransferase 2, mitochondrial (AGXT2)	OTO6QUTM	AGT2_HUMAN	Decreases Expression	[8]
cAMP-dependent protein kinase inhibitor beta (PKIB)	OT7C8GFN	IPKB_HUMAN	Increases Expression	[8]
Potassium channel subfamily K member 13 (KCNK13)	OTMOT2KX	KCNKD_HUMAN	Increases Expression	[8]
Serine/threonine-protein kinase Sgk2 (SGK2)	OTCTVSHF	SGK2_HUMAN	Increases Expression	[8]
Acetyl-coenzyme A synthetase, cytoplasmic (ACSS2)	OTB1FZJU	ACSA_HUMAN	Decreases Expression	[8]
Protein C19orf12 (C19ORF12)	OTVSJ1AR	CS012_HUMAN	Increases Expression	[8]
Ethanolamine kinase 2 (ETNK2)	OT5S1Z75	EKI2_HUMAN	Decreases Expression	[8]
Phosphatidylethanolamine N-methyltransferase (PEMT)	OTKXRUL9	PEMT_HUMAN	Increases Expression	[8]
SH3 domain-binding glutamic acid-rich-like protein 2 (SH3BGRL2)	OTOX4XT7	SH3L2_HUMAN	Increases Expression	[8]
Excitatory amino acid transporter 5 (SLC1A7)	OTVN5C6W	EAA5_HUMAN	Increases Expression	[9]
Podocalyxin (PODXL)	OTPNQXF3	PODXL_HUMAN	Decreases Expression	[9]
Class E basic helix-loop-helix protein 40 (BHLHE40)	OTITX14U	BHE40_HUMAN	Decreases Expression	[9]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Increases Expression	[9]
Branched-chain-amino-acid aminotransferase, mitochondrial (BCAT2)	OT8L6EGI	BCAT2_HUMAN	Increases Expression	[9]
Transcription factor MafG (MAFG)	OTBQFUZH	MAFG_HUMAN	Increases Expression	[9]
D-3-phosphoglycerate dehydrogenase (PHGDH)	OT1LMRTG	SERA_HUMAN	Increases Expression	[9]
TP53-regulated inhibitor of apoptosis 1 (TRIAP1)	OTEAUJXN	TRIA1_HUMAN	Decreases Expression	[9]
NUAK family SNF1-like kinase 1 (NUAK1)	OTLLHJJQ	NUAK1_HUMAN	Decreases Expression	[9]
Protein phosphatase 1 regulatory subunit 15A (PPP1R15A)	OTYG179K	PR15A_HUMAN	Increases Expression	[9]
Solute carrier organic anion transporter family member 2B1 (SLCO2B1)	OTERJ4VQ	SO2B1_HUMAN	Decreases Expression	[9]
Beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-N-acetylglucosaminyltransferase 3 (GCNT3)	OTQ9ALTR	GCNT3_HUMAN	Increases Expression	[9]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Affects Activity	[9]
Alpha-enolase (ENO1)	OTB1KWJS	ENOA_HUMAN	Increases Expression	[9]
Bifunctional glutamate/proline--tRNA ligase (EPRS1)	OTXK0FLB	SYEP_HUMAN	Increases Expression	[9]
Amino acid transporter heavy chain SLC3A2 (SLC3A2)	OTBR33M9	4F2_HUMAN	Increases Expression	[9]
Asparagine synthetase (ASNS)	OT8R922G	ASNS_HUMAN	Increases Expression	[9]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Increases Expression	[9]
RNA-binding protein RO60 (RO60)	OTLGM5A8	RO60_HUMAN	Decreases Expression	[9]
Retinoic acid receptor alpha (RARA)	OT192V9V	RARA_HUMAN	Decreases Expression	[9]
Histone H1.2 (H1-2)	OT0AVI4M	H12_HUMAN	Decreases Expression	[9]
Cyclic AMP-dependent transcription factor ATF-3 (ATF3)	OTC1UOHP	ATF3_HUMAN	Increases Expression	[9]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4)	OTRFV19J	ATF4_HUMAN	Affects Activity	[9]
Transcription factor E3 (TFE3)	OTM99ZWH	TFE3_HUMAN	Increases Expression	[9]
Retinoic acid receptor RXR-alpha (RXRA)	OTP1TBDM	RXRA_HUMAN	Decreases Expression	[9]
B-cell lymphoma 3 protein (BCL3)	OT1M5B95	BCL3_HUMAN	Decreases Expression	[9]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Decreases Expression	[9]
ETS domain-containing protein Elk-4 (ELK4)	OTVSSEOE	ELK4_HUMAN	Increases Expression	[9]
High affinity cationic amino acid transporter 1 (SLC7A1)	OTR2ZVA8	CTR1_HUMAN	Increases Expression	[9]
Cystathionine gamma-lyase (CTH)	OTC90LA0	CGL_HUMAN	Increases Expression	[9]
DNA damage-inducible transcript 3 protein (DDIT3)	OTI8YKKE	DDIT3_HUMAN	Increases Expression	[9]
Aryl hydrocarbon receptor (AHR)	OTFE4EYE	AHR_HUMAN	Affects Activity	[9]
Glycine--tRNA ligase (GARS1)	OT5B6R9Y	GARS_HUMAN	Increases Expression	[9]
Isoleucine--tRNA ligase, cytoplasmic (IARS1)	OT9WXH5N	SYIC_HUMAN	Increases Expression	[9]
Eukaryotic translation initiation factor 1 (EIF1)	OTB4GZ0V	EIF1_HUMAN	Increases Expression	[9]
Sodium- and chloride-dependent glycine transporter 1 (SLC6A9)	OTHRUON2	SC6A9_HUMAN	Increases Expression	[9]
Glutamate--cysteine ligase regulatory subunit (GCLM)	OT6CP234	GSH0_HUMAN	Increases Expression	[9]
Aldo-keto reductase family 1 member C2 (AKR1C2)	OTQ2XMO3	AK1C2_HUMAN	Increases Expression	[9]
Branched-chain-amino-acid aminotransferase, cytosolic (BCAT1)	OTYHXLWZ	BCAT1_HUMAN	Decreases Expression	[9]
Serine/threonine-protein kinase SIK1 (SIK1)	OT6FCHME	SIK1_HUMAN	Increases Expression	[9]
Large neutral amino acids transporter small subunit 1 (SLC7A5)	OT2WPVXD	LAT1_HUMAN	Increases Expression	[9]
1,4-alpha-glucan-branching enzyme (GBE1)	OTK2N05B	GLGB_HUMAN	Increases Expression	[9]
Adenylate cyclase type 1 (ADCY1)	OTSLLFZO	ADCY1_HUMAN	Decreases Expression	[9]
Ras-related protein Rab-31 (RAB31)	OTMLXQZ0	RAB31_HUMAN	Decreases Expression	[9]
Enhancer of filamentation 1 (NEDD9)	OTGCFN4M	CASL_HUMAN	Decreases Expression	[9]
Probable E3 ubiquitin-protein ligase HERC3 (HERC3)	OTWMKYD9	HERC3_HUMAN	Increases Expression	[9]
Nuclear factor erythroid 2-related factor 2 (NFE2L2)	OT0HENJ5	NF2L2_HUMAN	Affects Activity	[9]
Cyclin-G2 (CCNG2)	OTII38K2	CCNG2_HUMAN	Decreases Expression	[9]
Neuronal regeneration-related protein (NREP)	OT2AZPKK	NREP_HUMAN	Decreases Expression	[9]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Affects Activity	[9]
Dual specificity protein phosphatase 5 (DUSP5)	OTH96RA7	DUS5_HUMAN	Increases Expression	[9]
Glycerol-3-phosphate acyltransferase 3 (GPAT3)	OTJUGPK0	GPAT3_HUMAN	Increases Expression	[9]
Quinone oxidoreductase PIG3 (TP53I3)	OTSCM68G	QORX_HUMAN	Decreases Expression	[9]
Extracellular sulfatase Sulf-2 (SULF2)	OTIXMUVL	SULF2_HUMAN	Decreases Expression	[9]
Probable ATP-dependent RNA helicase DHX37 (DHX37)	OTM1A5KP	DHX37_HUMAN	Increases Expression	[9]
SH3 domain and tetratricopeptide repeat-containing protein 1 (SH3TC1)	OT0HYZIU	S3TC1_HUMAN	Increases Expression	[9]
Sortilin-related receptor (SORL1)	OTQ8FFNS	SORL_HUMAN	Decreases Expression	[9]
KICSTOR complex protein ITFG2 (ITFG2)	OT0NLZ8I	ITFG2_HUMAN	Increases Expression	[9]
Tumor protein p53-inducible nuclear protein 1 (TP53INP1)	OT2363Z9	T53I1_HUMAN	Decreases Expression	[9]
Protein FAM89A (FAM89A)	OTNASAXT	FA89A_HUMAN	Increases Expression	[9]
Spermatid perinuclear RNA-binding protein (STRBP)	OTU7XLZL	STRBP_HUMAN	Increases Expression	[9]
Growth/differentiation factor 15 (GDF15)	OTWQN50N	GDF15_HUMAN	Increases Expression	[9]
Protein orai-3 (ORAI3)	OTUP3OH3	ORAI3_HUMAN	Decreases Expression	[9]
Ferroptosis suppressor protein 1 (AIFM2)	OT57XWXO	FSP1_HUMAN	Increases Expression	[9]
Sulfiredoxin-1 (SRXN1)	OTYDBO4L	SRXN1_HUMAN	Increases Expression	[9]
Ankyrin repeat family A protein 2 (ANKRA2)	OTLSLV5A	ANRA2_HUMAN	Increases Expression	[9]
Gephyrin (GPHN)	OTAKK1SV	GEPH_HUMAN	Increases Expression	[9]
Ectonucleoside triphosphate diphosphohydrolase 7 (ENTPD7)	OT3QER33	ENTP7_HUMAN	Decreases Expression	[9]
DNA damage-inducible transcript 4 protein (DDIT4)	OTHY8SY4	DDIT4_HUMAN	Decreases Expression	[9]
Leucine--tRNA ligase, cytoplasmic (LARS1)	OT4557NF	SYLC_HUMAN	Increases Expression	[9]
Brefeldin A-inhibited guanine nucleotide-exchange protein 2 (ARFGEF2)	OTM3CQZT	BIG2_HUMAN	Increases Expression	[9]
Bifunctional epoxide hydrolase 2 (EPHX2)	OTPTRCNW	HYES_HUMAN	Affects Expression	[20]
Cytochrome P450 2J2 (CYP2J2)	OTJBTEH8	CP2J2_HUMAN	Affects Expression	[20]
Phospholipid-transporting ATPase ABCA1 (ABCA1)	OT94G6BQ	ABCA1_HUMAN	Increases Expression	[21]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Decreases Expression	[22]
Apolipoprotein A-I (APOA1)	OT5THARI	APOA1_HUMAN	Decreases Expression	[23]
Interstitial collagenase (MMP1)	OTI4I2V1	MMP1_HUMAN	Decreases Expression	[24]
Apolipoprotein B-100 (APOB)	OTH0UOCZ	APOB_HUMAN	Decreases Expression	[25]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Decreases Activity	[26]
72 kDa type IV collagenase (MMP2)	OT5NIWA2	MMP2_HUMAN	Decreases Expression	[24]
Matrilysin (MMP7)	OTVT3SEJ	MMP7_HUMAN	Decreases Expression	[24]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[27]
Proliferating cell nuclear antigen (PCNA)	OTHZ1RIA	PCNA_HUMAN	Increases Expression	[28]
Matrix metalloproteinase-9 (MMP9)	OTB2QDAV	MMP9_HUMAN	Decreases Expression	[24]
Fatty acid-binding protein, adipocyte (FABP4)	OT3DKFOU	FABP4_HUMAN	Increases Expression	[29]
Polyunsaturated fatty acid lipoxygenase ALOX12 (ALOX12)	OTFL5KR5	LOX12_HUMAN	Increases Expression	[29]
Nuclear factor NF-kappa-B p105 subunit (NFKB1)	OTNRRD8I	NFKB1_HUMAN	Affects Localization	[24]
Cytochrome P450 7A1 (CYP7A1)	OT8Z5KLD	CP7A1_HUMAN	Decreases Expression	[30]
Tumor necrosis factor receptor superfamily member 5 (CD40)	OT5YU2XB	TNR5_HUMAN	Decreases Expression	[22]
NF-kappa-B inhibitor alpha (NFKBIA)	OTFT924M	IKBA_HUMAN	Decreases Expression	[24]
CD40 ligand (CD40LG)	OT75Z6A6	CD40L_HUMAN	Decreases Expression	[31]
Peroxisome proliferator-activated receptor gamma (PPARG)	OTHMARHO	PPARG_HUMAN	Increases Expression	[21]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Decreases Expression	[28]
Cyclin-dependent kinase inhibitor 1B (CDKN1B)	OTNY5LLZ	CDN1B_HUMAN	Decreases Expression	[28]
Carnitine O-palmitoyltransferase 1, liver isoform (CPT1A)	OTI862QH	CPT1A_HUMAN	Increases Expression	[32]
5'-AMP-activated protein kinase subunit gamma-1 (PRKAG1)	OTW00PRY	AAKG1_HUMAN	Increases Expression	[24]
Oxysterols receptor LXR-beta (NR1H2)	OT4APA60	NR1H2_HUMAN	Increases Expression	[21]
Caveolin-1 (CAV1)	OTEZUR1L	CAV1_HUMAN	Increases Expression	[33]
Peroxisome proliferator-activated receptor delta (PPARD)	OTI4WTOP	PPARD_HUMAN	Increases Expression	[21]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[22]
Platelet-activating factor acetylhydrolase (PLA2G7)	OT6H6AMO	PAFA_HUMAN	Decreases Activity	[34]
Oxysterols receptor LXR-alpha (NR1H3)	OT54YZ9I	NR1H3_HUMAN	Increases Expression	[21]
Baculoviral IAP repeat-containing protein 3 (BIRC3)	OT3E95KB	BIRC3_HUMAN	Decreases Expression	[22]
Nuclear receptor subfamily 0 group B member 2 (NR0B2)	OT7UVICX	NR0B2_HUMAN	Increases Expression	[35]
Adiponectin (ADIPOQ)	OTNX23LE	ADIPO_HUMAN	Increases Expression	[31]
Bcl-2-related protein A1 (BCL2A1)	OTWRYSNA	B2LA1_HUMAN	Decreases Expression	[22]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Decreases Activity	[26]
Proprotein convertase subtilisin/kexin type 9 (PCSK9)	OTI0DU9Y	PCSK9_HUMAN	Increases Expression	[25]
Scavenger receptor class B member 1 (SCARB1)	OTAE1UA1	SCRB1_HUMAN	Increases Expression	[36]
NAD-dependent protein deacetylase sirtuin-1 (SIRT1)	OTAYZMOY	SIR1_HUMAN	Increases Expression	[37]
Tribbles homolog 3 (TRIB3)	OTG5OS7X	TRIB3_HUMAN	Decreases Expression	[38]
Semaphorin-6B (SEMA6B)	OT3VVVUO	SEM6B_HUMAN	Decreases Expression	[39]
Fibroblast growth factor 21 (FGF21)	OT3RXVRD	FGF21_HUMAN	Increases Expression	[40]
5'-AMP-activated protein kinase subunit beta-1 (PRKAB1)	OT1OG4QZ	AAKB1_HUMAN	Increases Phosphorylation	[24]
5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1)	OT7TNF0L	AAPK1_HUMAN	Decreases Response To Substance	[24]
HLA class I histocompatibility antigen, A alpha chain (HLA-A)	OTAH14LU	HLAA_HUMAN	Affects Response To Substance	[41]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Affects Response To Substance	[42]

Indication(s) of Rosuvastatin

Disease Entry	ICD 11	Status	REF
Arteriosclerosis	BD40	Approved	[4]
Hypercholesterolaemia	5C80.0	Approved	[5]
Hyperlipidemia, familial combined, LPL related	N.A.	Approved	[4]
Hypertriglyceridemia	5C80.1	Approved	[4]
Elevated C-reactive protein	MA14.15	Phase 3	[5]
Colon cancer	2B90.Z	Investigative	[4]
Precancerous condition	N.A.	Investigative	[4]
Stroke	8B20	Investigative	[4]

Rosuvastatin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
HMG-CoA reductase (HMGCR)	TTPADOQ	HMDH_HUMAN	Inhibitor	[43]

Rosuvastatin Interacts with 9 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[44]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[44]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[44]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[44]
Sodium/taurocholate cotransporting polypeptide (SLC10A1)	DT56EKP	NTCP_HUMAN	Substrate	[45]
Organic anion transporter 3 (SLC22A8)	DTVP67E	S22A8_HUMAN	Substrate	[46]
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTE2B1D	SO1A2_HUMAN	Substrate	[45]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[44]
Organic anion transporting polypeptide 2B1 (SLCO2B1)	DTPFTEQ	SO2B1_HUMAN	Substrate	[44]

Rosuvastatin Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[47]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[47]
Cytochrome P450 1B1 (CYP1B1)	DE9QHP6	CP1B1_HUMAN	Metabolism	[48]

Rosuvastatin Interacts with 3 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Increases ADR	[49]
Kinesin-like protein KIF6 (KIF6)	OTDH3MR4	KIF6_HUMAN	Increases ADR	[50]
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR)	OTRT3F3U	HMDH_HUMAN	Increases ADR	[51]

References

• [1] ClinicalTrials.gov (NCT00585143) Safety Study to Evaluate the Effects of Mild and Moderate Renal Impairment on the Pharmacokinetics of ABT-335 and Rosuvastatin When Administered Concomitantly
• [2] Fenofibrate FDA Label
• [3] 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: 7186).
• [4] Rosuvastatin FDA Label
• [5] 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: 2954).
• [6] Human UDP-glucuronosyltransferase (UGT)1A3 enzyme conjugates chenodeoxycholic acid in the liver. Hepatology. 2006 Nov;44(5):1158-70.
• [7] Linalool is a PPARalpha ligand that reduces plasma TG levels and rewires the hepatic transcriptome and plasma metabolome. J Lipid Res. 2014 Jun;55(6):1098-110.
• [8] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [9] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [10] Peroxisome proliferator-activated receptor alpha activators improve insulin sensitivity and reduce adiposity. J Biol Chem. 2000 Jun 2;275(22):16638-42.
• [11] Clinical pharmacokinetics of fibric acid derivatives (fibrates). Clin Pharmacokinet. 1998 Feb;34(2):155-62.
• [12] Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8.
• [13] The effect of fenofibrate on serum paraoxonase activity and inflammatory markers in patients with combined hyperlipidemia. Kardiol Pol. 2005 Jun;62(6):526-30.
• [14] In vitro and in vivo effects of the PPAR-alpha agonists fenofibrate and retinoic acid in endometrial cancer. Mol Cancer. 2006 Mar 28;5:13.
• [15] Delta5 desaturase mRNA levels are increased by simvastatin via SREBP-1 at early stages, not via PPARalpha, in THP-1 cells. Eur J Pharmacol. 2007 Oct 1;571(2-3):97-105.
• [16] Inhibiting wild-type and C299S mutant AKR1B10; a homologue of aldose reductase upregulated in cancers. Eur J Pharmacol. 2008 Apr 28;584(2-3):213-21.
• [17] Use of mRNA expression to detect the induction of drug metabolising enzymes in rat and human hepatocytes. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):86-96.
• [18] Fenofibrate suppresses microvascular inflammation and apoptosis through adenosine monophosphate-activated protein kinase activation. Metabolism. 2011 Apr;60(4):513-22.
• [19] Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development. Toxicol Sci. 2010 Dec; 118(2):485-500.
• [20] Expression of cytochrome P450 epoxygenases and soluble epoxide hydrolase is regulated by hypolipidemic drugs in dose-dependent manner. Toxicol Appl Pharmacol. 2018 Sep 15;355:156-163.
• [21] On the mechanism for PPAR agonists to enhance ABCA1 gene expression. Atherosclerosis. 2009 Aug;205(2):413-9. doi: 10.1016/j.atherosclerosis.2009.01.008. Epub 2009 Jan 19.
• [22] Fenofibrate induces effective apoptosis in mantle cell lymphoma by inhibiting the TNFalpha/NF-kappaB signaling axis. Leukemia. 2010 Aug;24(8):1476-86. doi: 10.1038/leu.2010.117. Epub 2010 Jun 3.
• [23] Negative regulation of the human apolipoprotein A-I promoter by fibrates can be attenuated by the interaction of the peroxisome proliferator-activated receptor with its response element. J Biol Chem. 1994 Dec 9;269(49):31012-8.
• [24] AMPK-dependent signaling modulates the suppression of invasion and migration by fenofibrate in CAL 27 oral cancer cells through NF-B pathway. Environ Toxicol. 2016 Jul;31(7):866-76. doi: 10.1002/tox.22097. Epub 2014 Dec 24.
• [25] Comparison of effects of bezafibrate and fenofibrate on circulating proprotein convertase subtilisin/kexin type 9 and adipocytokine levels in dyslipidemic subjects with impaired glucose tolerance or type 2 diabetes mellitus: results from a crossover study. Atherosclerosis. 2011 Jul;217(1):165-70. doi: 10.1016/j.atherosclerosis.2011.02.012. Epub 2011 Feb 22.
• [26] Association of CYP1A1 and CYP1B1 inhibition in in vitro assays with drug-induced liver injury. J Toxicol Sci. 2021;46(4):167-176. doi: 10.2131/jts.46.167.
• [27] Fenofibrate induces apoptotic injury in cultured human hepatocytes by inhibiting phosphorylation of Akt. Apoptosis. 2005 Mar;10(2):349-58. doi: 10.1007/s10495-005-0809-3.
• [28] Fenofibrate induced PPAR alpha expression was attenuated by oestrogen receptor alpha overexpression in Hep3B cells. Environ Toxicol. 2018 Feb;33(2):234-247. doi: 10.1002/tox.22511. Epub 2017 Nov 14.
• [29] Differential effects of peroxisome proliferator-activated receptor activators on the mRNA levels of genes involved in lipid metabolism in primary human monocyte-derived macrophages. Metabolism. 2003 May;52(5):652-7. doi: 10.1053/meta.2003.50100.
• [30] Fibrates modify the expression of key factors involved in bile-acid synthesis and biliary-lipid secretion in gallstone patients. Eur J Clin Pharmacol. 2004 Feb;59(12):855-61. doi: 10.1007/s00228-003-0704-1. Epub 2003 Dec 18.
• [31] Additive beneficial effects of fenofibrate combined with candesartan in the treatment of hypertriglyceridemic hypertensive patients. Diabetes Care. 2006 Feb;29(2):195-201. doi: 10.2337/diacare.29.02.06.dc05-1418.
• [32] Immunoselection and characterization of a human genomic PPAR binding fragment located within POTE genes. Biochimie. 2007 Mar;89(3):329-36. doi: 10.1016/j.biochi.2006.09.017. Epub 2006 Oct 18.
• [33] Rosiglitazone upregulates caveolin-1 expression in THP-1 cells through a PPAR-dependent mechanism. J Lipid Res. 2004 Nov;45(11):2015-24. doi: 10.1194/jlr.M400049-JLR200. Epub 2004 Aug 16.
• [34] The effect of orlistat and fenofibrate, alone or in combination, on small dense LDL and lipoprotein-associated phospholipase A2 in obese patients with metabolic syndrome. Atherosclerosis. 2007 Aug;193(2):428-37. doi: 10.1016/j.atherosclerosis.2006.07.010. Epub 2006 Sep 5.
• [35] Fenofibrate differentially regulates plasminogen activator inhibitor-1 gene expression via adenosine monophosphate-activated protein kinase-dependent induction of orphan nuclear receptor small heterodimer partner. Hepatology. 2009 Sep;50(3):880-92. doi: 10.1002/hep.23049.
• [36] Aspirin regulates expression and function of scavenger receptor-BI in macrophages: studies in primary human macrophages and in mice. FASEB J. 2006 Jul;20(9):1328-35. doi: 10.1096/fj.05-5368com.
• [37] Fenofibrate inhibits hypoxia-inducible factor-1 alpha and carbonic anhydrase expression through activation of AMP-activated protein kinase/HO-1/Sirt1 pathway in glioblastoma cells. Environ Toxicol. 2021 Dec;36(12):2551-2561. doi: 10.1002/tox.23369. Epub 2021 Sep 14.
• [38] PML-RAR interaction with TRIB3 impedes PPAR/RXR function and triggers dyslipidemia in acute promyelocytic leukemia. Theranostics. 2020 Aug 15;10(22):10326-10340. doi: 10.7150/thno.45924. eCollection 2020.
• [39] Effects of PPAR and RXR ligands in semaphorin 6B gene expression of human MCF-7 breast cancer cells. Int J Oncol. 2006 Apr;28(4):977-84.
• [40] Sodium butyrate stimulates expression of fibroblast growth factor 21 in liver by inhibition of histone deacetylase 3. Diabetes. 2012 Apr;61(4):797-806. doi: 10.2337/db11-0846. Epub 2012 Feb 14.
• [41] Association of Liver Injury From Specific Drugs, or Groups of?Drugs, With Polymorphisms in HLA and Other Genes in a?Genome-Wide Association Study. Gastroenterology. 2017 Apr;152(5):1078-1089. doi: 10.1053/j.gastro.2016.12.016. Epub 2016 Dec 30.
• [42] Interleukin-6 -174 G/C promoter polymorphism and effects of fenofibrate and simvastatin on inflammatory markers in hypercholesterolemic patients. Blood Coagul Fibrinolysis. 2006 Jan;17(1):35-8. doi: 10.1097/01.mbc.0000198052.65505.00.
• [43] New dimension of statin action on ApoB atherogenicity. Clin Cardiol. 2003 Jan;26(1 Suppl 1):I7-10.
• [44] Involvement of multiple transporters in the hepatobiliary transport of rosuvastatin. Drug Metab Dispos. 2008 Oct;36(10):2014-23.
• [45] Drug and bile acid transporters in rosuvastatin hepatic uptake: function, expression, and pharmacogenetics. Gastroenterology. 2006 May;130(6):1793-806.
• [46] The contribution of organic anion transporters OAT1 and OAT3 to the renal uptake of rosuvastatin. J Pharmacol Exp Ther. 2007 Sep;322(3):1221-7.
• [47] Effects of acid and lactone forms of eight HMG-CoA reductase inhibitors on CYP-mediated metabolism and MDR1-mediated transport. Pharm Res. 2006 Mar;23(3):506-12.
• [48] Pharmacokinetics of rosuvastatin when coadministered with rifampicin in healthy males: a randomized, single-blind, placebo-controlled, crossover study. Clin Ther. 2008 Jul;30(7):1283-9.
• [49] ABCG2 polymorphism is associated with the low-density lipoprotein cholesterol response to rosuvastatin. Clin Pharmacol Ther. 2010 May;87(5):558-62.
• [50] Association of the Trp719Arg polymorphism in kinesin-like protein 6 with myocardial infarction and coronary heart disease in 2 prospective trials: the CARE and WOSCOPS trials. J Am Coll Cardiol. 2008 Jan 29;51(4):435-43. doi: 10.1016/j.jacc.2007.05.057.
• [51] Pharmacogenetic study of statin therapy and cholesterol reduction. JAMA. 2004 Jun 16;291(23):2821-7. doi: 10.1001/jama.291.23.2821.