Details of the Drug Combination

General Information of Drug Combination (ID: DCLHRM0)

• Drug Combination Name: Atorvastatin + Rosuvastatin
• Indication: Type IIa and IIb Hypercholesterolaemia; Status: Phase 1 [1]
• Component Drugs:
  Atorvastatin (DMF28YC): Small molecular drug
  Rosuvastatin (DMMIQ7G): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Atorvastatin

Disease Entry	ICD 11	Status	REF
Acute coronary syndrome	BA41	Approved	[2]
Angina pectoris	BA40	Approved	[2]
Arteriosclerosis	BD40	Approved	[2]
Cardiovascular disease	BA00-BE2Z	Approved	[3]
Coronary atherosclerosis	N.A.	Approved	[2]
Hypercholesterolaemia	5C80.0	Approved	[2]
Hyperlipidemia	5C80.Z	Approved	[4]
Hyperlipidemia, familial combined, LPL related	N.A.	Approved	[2]
Hypertriglyceridemia	5C80.1	Approved	[2]
Inflammation	1A00-CA43.1	Approved	[2]
Non-insulin dependent diabetes	5A11	Approved	[2]
Psoriasis	EA90	Approved	[2]
Type-1/2 diabetes	5A10-5A11	Approved	[2]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[5]
Stroke	8B20	Investigative	[2]
Venous thromboembolism	BD72	Investigative	[2]

Atorvastatin Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
HMG-CoA reductase (HMGCR)	TTPADOQ	HMDH_HUMAN	Inhibitor	[11]
HUMAN MYD88NF-kappa-B proinflammatory pathway (MYD88-NFKB pathway)	TTDJB68	N.A.	Inhibitor	[12]

Atorvastatin Interacts with 7 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[13]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[14]
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTE2B1D	SO1A2_HUMAN	Substrate	[15]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[16]
Organic anion transporting polypeptide 2B1 (SLCO2B1)	DTPFTEQ	SO2B1_HUMAN	Substrate	[17]
Monocarboxylate transporter 1 (SLC16A1)	DT342ZG	MOT1_HUMAN	Substrate	[18]
Monocarboxylate transporter 2 (SLC16A7)	DTLT3UG	MOT2_HUMAN	Substrate	[19]

Atorvastatin Interacts with 6 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[20]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[21]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[22]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[23]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[24]
UDP-glucuronosyltransferase 1A3 (UGT1A3)	DEF2WXN	UD13_HUMAN	Metabolism	[25]

Atorvastatin Interacts with 93 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Stromelysin-1 (MMP3)	OTGBI74Z	MMP3_HUMAN	Increases ADR	[26]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Decreases Activity	[27]
Apolipoprotein E (APOE)	OTFOWL2H	APOE_HUMAN	Decreases Expression	[28]
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR)	OTRT3F3U	HMDH_HUMAN	Increases Expression	[29]
Kinesin-like protein KIF6 (KIF6)	OTDH3MR4	KIF6_HUMAN	Increases Response To Substance	[30]
ATP-binding cassette sub-family C member 2 (ABCC2)	OTJSIGV5	MRP2_HUMAN	Decreases Activity	[31]
Serum paraoxonase/arylesterase 1 (PON1)	OTD0Z2XO	PON1_HUMAN	Increases Expression	[32]
Cytochrome P450 2B6 (CYP2B6)	OTOYO4S7	CP2B6_HUMAN	Increases Expression	[33]
Nuclear receptor subfamily 1 group I member 3 (NR1I3)	OTS3SGH7	NR1I3_HUMAN	Increases Activity	[33]
Phospholipid-transporting ATPase ABCA1 (ABCA1)	OT94G6BQ	ABCA1_HUMAN	Decreases Expression	[28]
Sterol 26-hydroxylase, mitochondrial (CYP27A1)	OT649C01	CP27A_HUMAN	Decreases Expression	[28]
Angiopoietin-2 (ANGPT2)	OTEQK65P	ANGP2_HUMAN	Increases Expression	[8]
Urokinase-type plasminogen activator (PLAU)	OTX0QGKK	UROK_HUMAN	Decreases Expression	[8]
Thrombospondin-1 (THBS1)	OT0ECWK3	TSP1_HUMAN	Decreases Expression	[8]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Increases Expression	[8]
Nitric oxide synthase 3 (NOS3)	OTLDT7NR	NOS3_HUMAN	Increases Expression	[8]
Catalase (CAT)	OTHEBX9R	CATA_HUMAN	Increases Activity	[34]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[35]
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Increases Expression	[36]
Solute carrier family 2, facilitated glucose transporter member 2 (SLC2A2)	OTBL2W7R	GTR2_HUMAN	Decreases Expression	[36]
Hexokinase-4 (GCK)	OTR3Q0NN	HXK4_HUMAN	Decreases Expression	[36]
Toll-like receptor 4 (TLR4)	OTP7ML3S	TLR4_HUMAN	Increases Expression	[37]
Toll-like receptor 2 (TLR2)	OTGO5P4R	TLR2_HUMAN	Increases Expression	[37]
Prothrombin (F2)	OTNFSM49	THRB_HUMAN	Decreases Activity	[38]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[39]
Low-density lipoprotein receptor (LDLR)	OTH559LU	LDLR_HUMAN	Increases Expression	[29]
Insulin (INS)	OTZ85PDU	INS_HUMAN	Increases Expression	[40]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Decreases Expression	[9]
Interleukin-2 receptor subunit alpha (IL2RA)	OT0MWCHG	IL2RA_HUMAN	Affects Expression	[37]
Collagen alpha-1(I) chain (COL1A1)	OTI31178	CO1A1_HUMAN	Increases Expression	[41]
C-reactive protein (CRP)	OT0RFT8F	CRP_HUMAN	Decreases Expression	[42]
Transferrin receptor protein 1 (TFRC)	OT8ZPBDL	TFR1_HUMAN	Affects Expression	[37]
Osteocalcin (BGLAP)	OTK1YLWQ	OSTCN_HUMAN	Increases Expression	[41]
Apolipoprotein B-100 (APOB)	OTH0UOCZ	APOB_HUMAN	Decreases Expression	[43]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Affects Expression	[44]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[39]
Eukaryotic translation initiation factor 2 subunit 1 (EIF2S1)	OTM0GDTP	IF2A_HUMAN	Increases Phosphorylation	[45]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Decreases Expression	[46]
Endothelin-1 (EDN1)	OTZCACEG	EDN1_HUMAN	Decreases Expression	[47]
Intercellular adhesion molecule 1 (ICAM1)	OTTOIX77	ICAM1_HUMAN	Increases Expression	[9]
Integrin beta-1 (ITGB1)	OT6G1IAR	ITB1_HUMAN	Increases Expression	[48]
Rho-related GTP-binding protein RhoC (RHOC)	OTOLE1FT	RHOC_HUMAN	Decreases Localization	[49]
Monocyte differentiation antigen CD14 (CD14)	OT83GJ47	CD14_HUMAN	Decreases Expression	[50]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[51]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Decreases Expression	[46]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[51]
Integrin alpha-M (ITGAM)	OTAG6HWU	ITAM_HUMAN	Decreases Expression	[50]
Coagulation factor V (F5)	OTDMZ3LT	FA5_HUMAN	Decreases Activity	[38]
Bone morphogenetic protein 2 (BMP2)	OT23T37S	BMP2_HUMAN	Increases Expression	[41]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Decreases Expression	[46]
E-selectin (SELE)	OT33RZWY	LYAM2_HUMAN	Increases Expression	[9]
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A)	OT2D9DOV	TNR1A_HUMAN	Decreases Expression	[47]
Integrin alpha-X (ITGAX)	OTOGIMHE	ITAX_HUMAN	Decreases Expression	[50]
Tumor necrosis factor receptor superfamily member 5 (CD40)	OT5YU2XB	TNR5_HUMAN	Decreases Expression	[37]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[51]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[51]
Interleukin-12 subunit alpha (IL12A)	OTDQT8GI	IL12A_HUMAN	Decreases Expression	[52]
CD40 ligand (CD40LG)	OT75Z6A6	CD40L_HUMAN	Decreases Expression	[53]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[45]
Nicotinamide N-methyltransferase (NNMT)	OTFM38GU	NNMT_HUMAN	Increases Expression	[54]
T-lymphocyte activation antigen CD86 (CD86)	OTJCSBPC	CD86_HUMAN	Decreases Expression	[37]
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA)	OTTOMI8J	PK3CA_HUMAN	Decreases Expression	[39]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[51]
Cyclin-dependent kinase inhibitor 1B (CDKN1B)	OTNY5LLZ	CDN1B_HUMAN	Increases Expression	[51]
Tumor necrosis factor ligand superfamily member 6 (FASLG)	OTZARCHH	TNFL6_HUMAN	Increases Expression	[55]
Fatty acid synthase (FASN)	OTFII9KG	FAS_HUMAN	Increases Expression	[56]
Importin subunit alpha-1 (KPNA2)	OTU7FOE6	IMA1_HUMAN	Affects Localization	[57]
Microsomal triglyceride transfer protein large subunit (MTTP)	OTNUVSDT	MTP_HUMAN	Decreases Expression	[29]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Activity	[58]
Transforming protein RhoA (RHOA)	OT6YOJ9N	RHOA_HUMAN	Decreases Activity	[51]
Rho-related GTP-binding protein RhoB (RHOB)	OTHQFQF7	RHOB_HUMAN	Increases Expression	[49]
Cytochrome c (CYCS)	OTBFALJD	CYC_HUMAN	Affects Localization	[44]
E3 ubiquitin-protein ligase Mdm2 (MDM2)	OTOVXARF	MDM2_HUMAN	Increases Expression	[39]
CD83 antigen (CD83)	OT1V4WQF	CD83_HUMAN	Decreases Expression	[37]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[59]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	OT2YYI1A	MCL1_HUMAN	Decreases Expression	[51]
Peroxisome proliferator-activated receptor alpha (PPARA)	OTK095PP	PPARA_HUMAN	Decreases Expression	[60]
Sterol regulatory element-binding protein 2 (SREBF2)	OTBXUNPL	SRBP2_HUMAN	Increases Localization	[56]
5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1)	OT7TNF0L	AAPK1_HUMAN	Increases Activity	[54]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Activity	[58]
Serum paraoxonase/arylesterase 2 (PON2)	OT55NCTD	PON2_HUMAN	Increases Expression	[61]
Adiponectin (ADIPOQ)	OTNX23LE	ADIPO_HUMAN	Decreases Expression	[40]
Nuclear factor erythroid 2-related factor 2 (NFE2L2)	OT0HENJ5	NF2L2_HUMAN	Decreases Expression	[44]
Bcl-2 homologous antagonist/killer (BAK1)	OTDP6ILW	BAK_HUMAN	Increases Expression	[59]
NAD-dependent protein deacetylase sirtuin-1 (SIRT1)	OTAYZMOY	SIR1_HUMAN	Increases Phosphorylation	[54]
Eukaryotic translation initiation factor 2-alpha kinase 3 (EIF2AK3)	OT0DZGY4	E2AK3_HUMAN	Increases Response To Substance	[45]
Tumor necrosis factor ligand superfamily member 10 (TNFSF10)	OT4PXBTA	TNF10_HUMAN	Increases Response To Substance	[62]
Liver carboxylesterase 1 (CES1)	OT9L0LR8	EST1_HUMAN	Increases ADR	[26]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Transport	[63]
Solute carrier organic anion transporter family member 2B1 (SLCO2B1)	OTERJ4VQ	SO2B1_HUMAN	Increases Uptake	[64]
Solute carrier organic anion transporter family member 1B1 (SLCO1B1)	OTNEN8QK	SO1B1_HUMAN	Decreases Transport	[65]
Solute carrier organic anion transporter family member 1B3 (SLCO1B3)	OTOM3BUH	SO1B3_HUMAN	Increases Uptake	[64]
Sister chromatid cohesion protein DCC1 (DSCC1)	OTPUVLZT	DCC1_HUMAN	Affects Response To Substance	[66]

Indication(s) of Rosuvastatin

Disease Entry	ICD 11	Status	REF
Arteriosclerosis	BD40	Approved	[6]
Hypercholesterolaemia	5C80.0	Approved	[7]
Hyperlipidemia, familial combined, LPL related	N.A.	Approved	[6]
Hypertriglyceridemia	5C80.1	Approved	[6]
Elevated C-reactive protein	MA14.15	Phase 3	[7]
Colon cancer	2B90.Z	Investigative	[6]
Precancerous condition	N.A.	Investigative	[6]
Stroke	8B20	Investigative	[6]

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	[67]

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	[68]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[68]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[68]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[68]
Sodium/taurocholate cotransporting polypeptide (SLC10A1)	DT56EKP	NTCP_HUMAN	Substrate	[69]
Organic anion transporter 3 (SLC22A8)	DTVP67E	S22A8_HUMAN	Substrate	[70]
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTE2B1D	SO1A2_HUMAN	Substrate	[69]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[68]
Organic anion transporting polypeptide 2B1 (SLCO2B1)	DTPFTEQ	SO2B1_HUMAN	Substrate	[68]

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	[22]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[22]
Cytochrome P450 1B1 (CYP1B1)	DE9QHP6	CP1B1_HUMAN	Metabolism	[71]

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	[72]
Kinesin-like protein KIF6 (KIF6)	OTDH3MR4	KIF6_HUMAN	Increases ADR	[73]
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR)	OTRT3F3U	HMDH_HUMAN	Increases ADR	[74]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Hypercholesterolemia	DC4DJ66	N. A.	Phase 1	[75]

References

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