Details of the Drug Combination

General Information of Drug Combination (ID: DC5ROEX)

• Drug Combination Name: Atorvastatin + Colchicine
• Indication: Non ST Segment Elevation Acute Coronary Syndrome; Status: Phase 2 [1]
• Component Drugs:
  Atorvastatin (DMF28YC): Small molecular drug
  Colchicine (DM2POTE): 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	[13]
HUMAN MYD88NF-kappa-B proinflammatory pathway (MYD88-NFKB pathway)	TTDJB68	N.A.	Inhibitor	[14]

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	[15]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[16]
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTE2B1D	SO1A2_HUMAN	Substrate	[17]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[18]
Organic anion transporting polypeptide 2B1 (SLCO2B1)	DTPFTEQ	SO2B1_HUMAN	Substrate	[19]
Monocarboxylate transporter 1 (SLC16A1)	DT342ZG	MOT1_HUMAN	Substrate	[20]
Monocarboxylate transporter 2 (SLC16A7)	DTLT3UG	MOT2_HUMAN	Substrate	[21]

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	[22]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[23]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[24]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[25]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[26]
UDP-glucuronosyltransferase 1A3 (UGT1A3)	DEF2WXN	UD13_HUMAN	Metabolism	[27]

Atorvastatin Interacts with 47 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Stromelysin-1 (MMP3)	OTGBI74Z	MMP3_HUMAN	Increases ADR	[28]
Kinesin-like protein KIF6 (KIF6)	OTDH3MR4	KIF6_HUMAN	Increases Response To Substance	[29]
Nuclear receptor subfamily 1 group I member 3 (NR1I3)	OTS3SGH7	NR1I3_HUMAN	Increases Activity	[30]
Phospholipid-transporting ATPase ABCA1 (ABCA1)	OT94G6BQ	ABCA1_HUMAN	Decreases Expression	[31]
Sterol 26-hydroxylase, mitochondrial (CYP27A1)	OT649C01	CP27A_HUMAN	Decreases Expression	[31]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[32]
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Increases Expression	[33]
Solute carrier family 2, facilitated glucose transporter member 2 (SLC2A2)	OTBL2W7R	GTR2_HUMAN	Decreases Expression	[33]
Hexokinase-4 (GCK)	OTR3Q0NN	HXK4_HUMAN	Decreases Expression	[33]
Prothrombin (F2)	OTNFSM49	THRB_HUMAN	Decreases Activity	[34]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[35]
Interleukin-2 receptor subunit alpha (IL2RA)	OT0MWCHG	IL2RA_HUMAN	Affects Expression	[36]
Collagen alpha-1(I) chain (COL1A1)	OTI31178	CO1A1_HUMAN	Increases Expression	[37]
C-reactive protein (CRP)	OT0RFT8F	CRP_HUMAN	Decreases Expression	[38]
Osteocalcin (BGLAP)	OTK1YLWQ	OSTCN_HUMAN	Increases Expression	[37]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Affects Expression	[39]
Eukaryotic translation initiation factor 2 subunit 1 (EIF2S1)	OTM0GDTP	IF2A_HUMAN	Increases Phosphorylation	[40]
Rho-related GTP-binding protein RhoC (RHOC)	OTOLE1FT	RHOC_HUMAN	Decreases Localization	[41]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[42]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Decreases Expression	[43]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Decreases Expression	[43]
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A)	OT2D9DOV	TNR1A_HUMAN	Decreases Expression	[44]
Integrin alpha-X (ITGAX)	OTOGIMHE	ITAX_HUMAN	Decreases Expression	[45]
Tumor necrosis factor receptor superfamily member 5 (CD40)	OT5YU2XB	TNR5_HUMAN	Decreases Expression	[36]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[42]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[42]
Interleukin-12 subunit alpha (IL12A)	OTDQT8GI	IL12A_HUMAN	Decreases Expression	[46]
CD40 ligand (CD40LG)	OT75Z6A6	CD40L_HUMAN	Decreases Expression	[47]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[40]
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA)	OTTOMI8J	PK3CA_HUMAN	Decreases Expression	[35]
Cyclin-dependent kinase inhibitor 1B (CDKN1B)	OTNY5LLZ	CDN1B_HUMAN	Increases Expression	[42]
Tumor necrosis factor ligand superfamily member 6 (FASLG)	OTZARCHH	TNFL6_HUMAN	Increases Expression	[48]
Importin subunit alpha-1 (KPNA2)	OTU7FOE6	IMA1_HUMAN	Affects Localization	[49]
Microsomal triglyceride transfer protein large subunit (MTTP)	OTNUVSDT	MTP_HUMAN	Decreases Expression	[50]
Rho-related GTP-binding protein RhoB (RHOB)	OTHQFQF7	RHOB_HUMAN	Increases Expression	[41]
Cytochrome c (CYCS)	OTBFALJD	CYC_HUMAN	Affects Localization	[39]
CD83 antigen (CD83)	OT1V4WQF	CD83_HUMAN	Decreases Expression	[36]
Sterol regulatory element-binding protein 2 (SREBF2)	OTBXUNPL	SRBP2_HUMAN	Increases Localization	[51]
5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1)	OT7TNF0L	AAPK1_HUMAN	Increases Activity	[52]
Bcl-2 homologous antagonist/killer (BAK1)	OTDP6ILW	BAK_HUMAN	Increases Expression	[53]
Eukaryotic translation initiation factor 2-alpha kinase 3 (EIF2AK3)	OT0DZGY4	E2AK3_HUMAN	Increases Response To Substance	[40]
Tumor necrosis factor ligand superfamily member 10 (TNFSF10)	OT4PXBTA	TNF10_HUMAN	Increases Response To Substance	[54]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Transport	[55]
Solute carrier organic anion transporter family member 2B1 (SLCO2B1)	OTERJ4VQ	SO2B1_HUMAN	Increases Uptake	[56]
Solute carrier organic anion transporter family member 1B1 (SLCO1B1)	OTNEN8QK	SO1B1_HUMAN	Decreases Transport	[57]
Solute carrier organic anion transporter family member 1B3 (SLCO1B3)	OTOM3BUH	SO1B3_HUMAN	Increases Uptake	[56]
Sister chromatid cohesion protein DCC1 (DSCC1)	OTPUVLZT	DCC1_HUMAN	Affects Response To Substance	[58]

Indication(s) of Colchicine

Disease Entry	ICD 11	Status	REF
Acute gout flare	FA25.0	Approved	[6]
Acute gouty arthritis	FA25.0	Approved	[7]
Gout	FA25	Approved	[8]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[9]
Familial Mediterranean fever	N.A.	Investigative	[8]

Colchicine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tubulin (TUB)	TTML2WA	NOUNIPROTAC	Binder	[60]

Colchicine Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 1 (ABCC1)	DTSYQGK	MRP1_HUMAN	Substrate	[61]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[62]

Colchicine Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[63]

Colchicine Interacts with 85 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[64]
Succinate dehydrogenase assembly factor 1, mitochondrial (SDHAF1)	OTDG5VW7	SDHF1_HUMAN	Decreases Expression	[59]
E3 ubiquitin-protein ligase TRIM38 (TRIM38)	OT6SP1M9	TRI38_HUMAN	Decreases Expression	[59]
Ectoderm-neural cortex protein 1 (ENC1)	OTJEUB6U	ENC1_HUMAN	Decreases Expression	[59]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Decreases Expression	[59]
Plexin-B2 (PLXNB2)	OT56I2VD	PLXB2_HUMAN	Decreases Expression	[59]
E3 ubiquitin-protein ligase RNF113A (RNF113A)	OTR6N7HU	R113A_HUMAN	Decreases Expression	[59]
DNA repair protein RAD51 homolog 3 (RAD51C)	OTUD6SY5	RA51C_HUMAN	Decreases Expression	[59]
TP53-regulated inhibitor of apoptosis 1 (TRIAP1)	OTEAUJXN	TRIA1_HUMAN	Decreases Expression	[59]
Dual specificity protein phosphatase 14 (DUSP14)	OTGODFCR	DUS14_HUMAN	Decreases Expression	[59]
Kinesin-like protein KIF20A (KIF20A)	OTXOQHE0	KI20A_HUMAN	Decreases Expression	[59]
CUGBP Elav-like family member 2 (CELF2)	OTLJJ4VT	CELF2_HUMAN	Increases Expression	[65]
Prothrombin (F2)	OTNFSM49	THRB_HUMAN	Affects Activity	[66]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Expression	[66]
Transcription factor Jun (JUN)	OTCYBO6X	JUN_HUMAN	Increases Phosphorylation	[67]
Keratin, type I cytoskeletal 18 (KRT18)	OTVLQFIP	K1C18_HUMAN	Decreases Expression	[68]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[69]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[70]
Microtubule-associated protein 2 (MAP2)	OT6UYT3X	MTAP2_HUMAN	Decreases Expression	[71]
Cadherin-1 (CDH1)	OTFJMXPM	CADH1_HUMAN	Affects Activity	[72]
CD59 glycoprotein (CD59)	OTSUMQDH	CD59_HUMAN	Increases Mutagenesis	[73]
Tyrosine aminotransferase (TAT)	OT2CJ91O	ATTY_HUMAN	Decreases Expression	[74]
NADPH:adrenodoxin oxidoreductase, mitochondrial (FDXR)	OTPDCK1F	ADRO_HUMAN	Decreases Expression	[59]
Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2)	OTIN6G20	CPT2_HUMAN	Decreases Expression	[59]
M-phase inducer phosphatase 1 (CDC25A)	OTSLKKCO	MPIP1_HUMAN	Decreases Expression	[59]
Sodium-dependent serotonin transporter (SLC6A4)	OT6FGDLW	SC6A4_HUMAN	Decreases Expression	[71]
Replication factor C subunit 1 (RFC1)	OT3L5PK3	RFC1_HUMAN	Decreases Expression	[59]
DNA damage-inducible transcript 3 protein (DDIT3)	OTI8YKKE	DDIT3_HUMAN	Increases Expression	[75]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Decreases Expression	[59]
Tumor necrosis factor ligand superfamily member 9 (TNFSF9)	OTV9L89D	TNFL9_HUMAN	Decreases Expression	[59]
RNA-binding protein 34 (RBM34)	OTX3LUGI	RBM34_HUMAN	Decreases Expression	[59]
Mitogen-activated protein kinase 8 (MAPK8)	OTEREYS5	MK08_HUMAN	Increases Phosphorylation	[67]
Mitogen-activated protein kinase 9 (MAPK9)	OTCEVJ9E	MK09_HUMAN	Increases Phosphorylation	[67]
LIM/homeobox protein Lhx2 (LHX2)	OTK61NP8	LHX2_HUMAN	Decreases Expression	[59]
DNA mismatch repair protein Msh6 (MSH6)	OT46FP09	MSH6_HUMAN	Decreases Expression	[59]
RecQ-like DNA helicase BLM (BLM)	OTEJOAJX	BLM_HUMAN	Decreases Expression	[59]
Ataxin-1 (ATXN1)	OTQF0HNR	ATX1_HUMAN	Decreases Expression	[59]
Ras-related protein Rap-2b (RAP2B)	OTD2NDQP	RAP2B_HUMAN	Decreases Expression	[59]
Protein BTG1 (BTG1)	OTVJ2CDM	BTG1_HUMAN	Decreases Expression	[59]
Protein BTG2 (BTG2)	OTZF6K1H	BTG2_HUMAN	Decreases Expression	[59]
Transcription factor E2F1 (E2F1)	OTLKYBBC	E2F1_HUMAN	Decreases Expression	[59]
Myelin transcription factor 1 (MYT1)	OTC3660I	MYT1_HUMAN	Increases Phosphorylation	[76]
DNA-binding protein inhibitor ID-3 (ID3)	OTUULW5Z	ID3_HUMAN	Decreases Expression	[59]
Tripartite motif-containing protein 26 (TRIM26)	OTS0DJIP	TRI26_HUMAN	Decreases Expression	[59]
E3 ubiquitin-protein ligase TRIM32 (TRIM32)	OTJOV0PG	TRI32_HUMAN	Decreases Expression	[59]
Chromatin assembly factor 1 subunit A (CHAF1A)	OTXSSY4H	CAF1A_HUMAN	Decreases Expression	[59]
Chromatin assembly factor 1 subunit B (CHAF1B)	OTOMK4KH	CAF1B_HUMAN	Decreases Expression	[59]
DNA topoisomerase 3-alpha (TOP3A)	OT3CKUI9	TOP3A_HUMAN	Decreases Expression	[59]
Oligodendrocyte transcription factor 2 (OLIG2)	OTMCN6D3	OLIG2_HUMAN	Decreases Expression	[71]
Protein BTG3 (BTG3)	OT9ANHVT	BTG3_HUMAN	Decreases Expression	[59]
Protein-tyrosine kinase 2-beta (PTK2B)	OTGAS0I8	FAK2_HUMAN	Increases Phosphorylation	[65]
Histone RNA hairpin-binding protein (SLBP)	OTVYYQRT	SLBP_HUMAN	Decreases Expression	[59]
Nuclear factor of activated T-cells, cytoplasmic 4 (NFATC4)	OTTDCUAO	NFAC4_HUMAN	Decreases Localization	[77]
Neutral amino acid transporter B(0) (SLC1A5)	OTE2H26Q	AAAT_HUMAN	Decreases Expression	[59]
E3 ubiquitin-protein ligase RNF19B (RNF19B)	OTYCWKBP	RN19B_HUMAN	Decreases Expression	[59]
Protein MCM10 homolog (MCM10)	OTV0O3JN	MCM10_HUMAN	Decreases Expression	[59]
Partner and localizer of BRCA2 (PALB2)	OT6DNDBG	PALB2_HUMAN	Decreases Expression	[59]
E3 ubiquitin-protein ligase TRIM22 (TRIM22)	OTJBLG5R	TRI22_HUMAN	Decreases Expression	[59]
Leucine-rich repeat-containing protein 47 (LRRC47)	OTSE8NAO	LRC47_HUMAN	Decreases Expression	[59]
Protein tyrosine phosphatase type IVA 1 (PTP4A1)	OTK0NFXJ	TP4A1_HUMAN	Decreases Expression	[59]
Cytochrome c oxidase assembly factor 7 (COA7)	OTRQJYL6	COA7_HUMAN	Decreases Expression	[59]
Mitochondrial potassium channel (CCDC51)	OTOJNHNA	MITOK_HUMAN	Decreases Expression	[59]
Integrator complex subunit 15 (INTS15)	OT3O4INM	INT15_HUMAN	Decreases Expression	[59]
Pleckstrin homology domain-containing family F member 1 (PLEKHF1)	OT9OL16U	PKHF1_HUMAN	Decreases Expression	[59]
Krueppel-like factor 6 (KLF6)	OTQY9S7F	KLF6_HUMAN	Increases Expression	[59]
Cell division control protein 6 homolog (CDC6)	OTX93FE7	CDC6_HUMAN	Decreases Expression	[59]
Protein orai-3 (ORAI3)	OTUP3OH3	ORAI3_HUMAN	Decreases Expression	[59]
Protein pelota homolog (PELO)	OTF3WLIM	PELO_HUMAN	Decreases Expression	[59]
TIMELESS-interacting protein (TIPIN)	OT9PZHXV	TIPIN_HUMAN	Decreases Expression	[59]
tRNA pseudouridine(38/39) synthase (PUS3)	OT6WG6M2	PUS3_HUMAN	Decreases Expression	[59]
Transmembrane protein 185B (TMEM185B)	OTGNYS0J	T185B_HUMAN	Decreases Expression	[59]
Interferon-stimulated 20 kDa exonuclease-like 2 (ISG20L2)	OT3Q11WQ	I20L2_HUMAN	Decreases Expression	[59]
GrpE protein homolog 1, mitochondrial (GRPEL1)	OT8O00YJ	GRPE1_HUMAN	Decreases Expression	[59]
p53-induced death domain-containing protein 1 (PIDD1)	OTWFM930	PIDD1_HUMAN	Decreases Expression	[59]
Fructose-2,6-bisphosphatase TIGAR (TIGAR)	OTR7NMRJ	TIGAR_HUMAN	Decreases Expression	[59]
DNA damage-inducible transcript 4 protein (DDIT4)	OTHY8SY4	DDIT4_HUMAN	Decreases Expression	[59]
Homologous-pairing protein 2 homolog (PSMC3IP)	OT9UB5UO	HOP2_HUMAN	Decreases Expression	[59]
Protein CLN8 (CLN8)	OT0D4CB5	CLN8_HUMAN	Decreases Expression	[59]
rRNA methyltransferase 2, mitochondrial (MRM2)	OTRYA1HU	MRM2_HUMAN	Decreases Expression	[59]
Frizzled-1 (FZD1)	OTZATHVS	FZD1_HUMAN	Decreases Expression	[59]
SH3 and multiple ankyrin repeat domains protein 2 (SHANK2)	OTSQTPFQ	SHAN2_HUMAN	Decreases Expression	[71]
5'-AMP-activated protein kinase subunit beta-1 (PRKAB1)	OT1OG4QZ	AAKB1_HUMAN	Decreases Expression	[59]
Pleckstrin homology-like domain family A member 3 (PHLDA3)	OTXFUDO2	PHLA3_HUMAN	Decreases Expression	[59]
Sestrin-1 (SESN1)	OTSFDZWL	SESN1_HUMAN	Decreases Expression	[59]
ATP-binding cassette sub-family A member 13 (ABCA13)	OTTHTUQN	ABCAD_HUMAN	Affects Response To Substance	[78]

References

• [1] ClinicalTrials.gov (NCT05250596) COLchicine On-admission to Reduce Inflammation in Acute Coronary Syndrome (COLOR-ACS)
• [2] Atorvastatin FDA Label
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (ANDA) 205945.
• [5] ClinicalTrials.gov (NCT04380402) Atorvastatin in COVID-19. U.S. National Institutes of Health.
• [6] FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (NDA) 022351
• [7] 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: 7526).
• [8] Colchicine FDA Label
• [9] ClinicalTrials.gov (NCT04322565) Colchicine Counteracting Inflammation in COVID-19 Pneumonia. U.S. National Institutes of Health.
• [10] Atorvastatin affects several angiogenic mediators in human endothelial cells. Endothelium. 2005 Sep-Dec;12(5-6):233-41.
• [11] Markers of inflammation, thrombosis and endothelial activation correlate with carotid IMT regression in stable coronary disease after atorvastatin treatment. Nutr Metab Cardiovasc Dis. 2009 Sep;19(7):481-90. doi: 10.1016/j.numecd.2008.10.003. Epub 2009 Jan 26.
• [12] Simvastatin reduces VCAM-1 expression in human umbilical vein endothelial cells exposed to lipopolysaccharide. Inflamm Res. 2012 May;61(5):485-91. doi: 10.1007/s00011-012-0435-9. Epub 2012 Jan 15.
• [13] Equally potent inhibitors of cholesterol synthesis in human hepatocytes have distinguishable effects on different cytochrome P450 enzymes. Biopharm Drug Dispos. 2000 Dec;21(9):353-64.
• [14] Statin therapy in COVID-19 infection. Eur Heart J Cardiovasc Pharmacother. 2020 Apr 29. pii: pvaa042.
• [15] Tarascon Pocket Pharmacopoeia 2018 Classic Shirt-Pocket Edition.
• [16] Rifampicin alters atorvastatin plasma concentration on the basis of SLCO1B1 521T>C polymorphism. Clin Chim Acta. 2009 Jul;405(1-2):49-52.
• [17] Influence of the flavonoids apigenin, kaempferol, and quercetin on the function of organic anion transporting polypeptides 1A2 and 2B1. Biochem Pharmacol. 2010 Dec 1;80(11):1746-53.
• [18] FDA Drug Development and Drug Interactions
• [19] Human platelets express organic anion-transporting peptide 2B1, an uptake transporter for atorvastatin. Drug Metab Dispos. 2009 May;37(5):1129-37.
• [20] H+-coupled nutrient, micronutrient and drug transporters in the mammalian small intestine. Exp Physiol. 2007 Jul;92(4):603-19.
• [21] Monocarboxylate Transporters in Drug Disposition: Role in the Toxicokinetics and Toxicodynamics of the Drug of Abuse GHB.
• [22] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [23] Atorvastatin glucuronidation is minimally and nonselectively inhibited by the fibrates gemfibrozil, fenofibrate, and fenofibric acid. Drug Metab Dispos. 2007 Aug;35(8):1315-24.
• [24] 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.
• [25] Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers.
• [26] Role of cytochrome P450 2C8 in drug metabolism and interactions. Pharmacol Rev. 2016 Jan;68(1):168-241.
• [27] UGT1A1*28 is associated with decreased systemic exposure of atorvastatin lactone. Mol Diagn Ther. 2013 Aug;17(4):233-7.
• [28] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [29] [Association of a polymorphic marker Trp719Arg of KIF6 gene with effects of atorvastatin and simvastatin in patients with early ischemic heart disease]. Kardiologiia. 2011;51(9):4-12.
• [30] Identification of HMG-CoA reductase inhibitors as activators for human, mouse and rat constitutive androstane receptor. Drug Metab Dispos. 2005 Jul;33(7):924-9.
• [31] Effects of rosiglitazone and atorvastatin on the expression of genes that control cholesterol homeostasis in differentiating monocytes. Biochem Pharmacol. 2006 Feb 28;71(5):605-14.
• [32] A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. Toxicol Sci. 2013 Nov;136(1):216-41.
• [33] Involvement of pregnane X receptor in the impaired glucose utilization induced by atorvastatin in hepatocytes. Biochem Pharmacol. 2016 Jan 15;100:98-111.
• [34] Atorvastatin and quinapril inhibit blood coagulation in patients with coronary artery disease following 28 days of therapy. J Thromb Haemost. 2006 Nov;4(11):2397-404. doi: 10.1111/j.1538-7836.2006.02165.x. Epub 2006 Aug 14.
• [35] Atorvastatin induces MicroRNA-145 expression in HEPG2 cells via regulation of the PI3K/AKT signalling pathway. Chem Biol Interact. 2018 May 1;287:32-40. doi: 10.1016/j.cbi.2018.04.005. Epub 2018 Apr 6.
• [36] Differential effects of statins on relevant functions of human monocyte-derived dendritic cells. J Leukoc Biol. 2006 Mar;79(3):529-38. doi: 10.1189/jlb.0205064. Epub 2005 Dec 30.
• [37] Simvastatin and atorvastatin enhance gene expression of collagen type 1 and osteocalcin in primary human osteoblasts and MG-63 cultures. J Cell Biochem. 2007 Aug 15;101(6):1430-8. doi: 10.1002/jcb.21259.
• [38] Effects of atorvastatin on inflammation and oxidative stress. Heart Vessels. 2005 Jul;20(4):133-6. doi: 10.1007/s00380-005-0833-9.
• [39] Atorvastatin induces mitochondrial dysfunction and cell apoptosis in HepG2 cells via inhibition of the Nrf2 pathway. J Appl Toxicol. 2019 Oct;39(10):1394-1404. doi: 10.1002/jat.3825. Epub 2019 Aug 18.
• [40] Inhibition of autophagy enhances anticancer effects of atorvastatin in digestive malignancies. Cancer Res. 2010 Oct 1;70(19):7699-709. doi: 10.1158/0008-5472.CAN-10-1626. Epub 2010 Sep 28.
• [41] Combination of atorvastatin and celecoxib synergistically induces cell cycle arrest and apoptosis in colon cancer cells. Int J Cancer. 2008 May 1;122(9):2115-24. doi: 10.1002/ijc.23315.
• [42] RhoA GTPase inactivation by statins induces osteosarcoma cell apoptosis by inhibiting p42/p44-MAPKs-Bcl-2 signaling independently of BMP-2 and cell differentiation. Cell Death Differ. 2006 Nov;13(11):1845-56. doi: 10.1038/sj.cdd.4401873. Epub 2006 Feb 10.
• [43] Simvastatin reduces expression of cytokines interleukin-6, interleukin-8, and monocyte chemoattractant protein-1 in circulating monocytes from hypercholesterolemic patients. Arterioscler Thromb Vasc Biol. 2002 Jul 1;22(7):1194-9. doi: 10.1161/01.atv.0000022694.16328.cc.
• [44] The effects of atorvastatin (10 mg) on systemic inflammation in heart failure. Am J Cardiol. 2005 Dec 15;96(12):1699-704. doi: 10.1016/j.amjcard.2005.07.092. Epub 2005 Oct 28.
• [45] Integrin expression on monocytes and lymphocytes in unstable angina short term effects of atorvastatin. Rom J Intern Med. 2007;45(2):193-9.
• [46] Treatment with atorvastatin alters the ratio of interleukin-12/interleukin-10 gene expression [corrected]. Eur J Clin Invest. 2003 Jan;33(1):88-91. doi: 10.1046/j.1365-2362.2003.01105.x.
• [47] Effect of atorvastatin on circulating proinflammatory T-lymphocyte subsets and soluble CD40 ligand in patients with stable coronary artery disease--a randomized, placebo-controlled study. Am Heart J. 2006 Jan;151(1):139. doi: 10.1016/j.ahj.2005.10.006.
• [48] Decreased circulating Fas ligand in patients with familial combined hyperlipidemia or carotid atherosclerosis: normalization by atorvastatin. J Am Coll Cardiol. 2004 Apr 7;43(7):1188-94. doi: 10.1016/j.jacc.2003.10.046.
• [49] Effect of Ivermectin and Atorvastatin on Nuclear Localization of Importin Alpha and Drug Target Expression Profiling in Host Cells from Nasopharyngeal Swabs of SARS-CoV-2- Positive Patients. Viruses. 2021 Oct 15;13(10):2084. doi: 10.3390/v13102084.
• [50] Differential regulation of apolipoprotein B secretion from HepG2 cells by two HMG-CoA reductase inhibitors, atorvastatin and simvastatin. J Lipid Res. 1999 Jun;40(6):1078-89.
• [51] Effect of atorvastatin, simvastatin, and lovastatin on the metabolism of cholesterol and triacylglycerides in HepG2 cells. Biochem Pharmacol. 2001 Dec 1;62(11):1545-55. doi: 10.1016/s0006-2952(01)00790-0.
• [52] Atorvastatin and pravastatin stimulate nitric oxide and reactive oxygen species generation, affect mitochondrial network architecture and elevate nicotinamide N-methyltransferase level in endothelial cells. J Appl Toxicol. 2021 Jul;41(7):1076-1088. doi: 10.1002/jat.4094. Epub 2020 Oct 19.
• [53] Atorvastatin mediates increases in intralesional BAX and BAK expression in human end-stage abdominal aortic aneurysms. Can J Physiol Pharmacol. 2009 Nov;87(11):915-22. doi: 10.1139/y09-085.
• [54] Regulation of apoptosis in human melanoma and neuroblastoma cells by statins, sodium arsenite and TRAIL: a role of combined treatment versus monotherapy. Apoptosis. 2011 Dec;16(12):1268-84.
• [55] Atorvastatin transport in the Caco-2 cell model: contributions of P-glycoprotein and the proton-monocarboxylic acid co-transporter. Pharm Res. 2000 Feb;17(2):209-15. doi: 10.1023/a:1007525616017.
• [56] The influence of oral antidiabetic drugs on cellular drug uptake mediated by hepatic OATP family members. Basic Clin Pharmacol Toxicol. 2013 Apr;112(4):244-50. doi: 10.1111/bcpt.12031. Epub 2012 Dec 6.
• [57] Functional characterization of SLCO1B1 (OATP-C) variants, SLCO1B1*5, SLCO1B1*15 and SLCO1B1*15+C1007G, by using transient expression systems of HeLa and HEK293 cells. Pharmacogenet Genomics. 2005 Jul;15(7):513-22.
• [58] Identification of target and pathway of aspirin combined with Lipitor treatment in prostate cancer through integrated bioinformatics analysis. Toxicol Appl Pharmacol. 2022 Oct 1;452:116169. doi: 10.1016/j.taap.2022.116169. Epub 2022 Aug 1.
• [59] Utilization of CDKN1A/p21 gene for class discrimination of DNA damage-induced clastogenicity. Toxicology. 2014 Jan 6;315:8-16. doi: 10.1016/j.tox.2013.10.009. Epub 2013 Nov 6.
• [60] Vitamin K3 disrupts the microtubule networks by binding to tubulin: a novel mechanism of its antiproliferative activity. Biochemistry. 2009 Jul 28;48(29):6963-74.
• [61] Pharmacological characterization of the murine and human orthologs of multidrug-resistance protein in transfected human embryonic kidney cells. Mol Pharmacol. 1997 Sep;52(3):344-53.
• [62] Nilotinib (AMN107, Tasigna) reverses multidrug resistance by inhibiting the activity of the ABCB1/Pgp and ABCG2/BCRP/MXR transporters. Biochem Pharmacol. 2009 Jul 15;78(2):153-61.
• [63] Colchicine down-regulates cytochrome P450 2B6, 2C8, 2C9, and 3A4 in human hepatocytes by affecting their glucocorticoid receptor-mediated regulation. Mol Pharmacol. 2003 Jul;64(1):160-9.
• [64] Analysis of ATP-binding cassette transporter expression in drug-selected cell lines by a microarray dedicated to multidrug resistance. Mol Pharmacol. 2004 Dec;66(6):1397-405. doi: 10.1124/mol.104.005009. Epub 2004 Sep 1.
• [65] Discovery of a novel compound: insight into mechanisms for acrylamide-induced axonopathy and colchicine-induced apoptotic neuronal cell death. Brain Res. 2001 Aug 3;909(1-2):8-19. doi: 10.1016/s0006-8993(01)02608-7.
• [66] [Colchicine in chronic liver disease of alcoholic etiology. Double-blind, randomized study of its effects on blood levels of plasma proteins and clinical course in patients]. Rev Assoc Med Bras (1992). 1995 May-Jun;41(3):207-12.
• [67] Nocodazole-induced p53-dependent c-Jun N-terminal kinase activation reduces apoptosis in human colon carcinoma HCT116 cells. J Biol Chem. 2002 Nov 15;277(46):43648-58. doi: 10.1074/jbc.M203214200. Epub 2002 Sep 6.
• [68] The stability of cytokeratin 18 in human liver cells during colchicine-induced microtubule disruption. Food Chem Toxicol. 2001 Jan;39(1):85-9. doi: 10.1016/s0278-6915(00)00113-7.
• [69] Investigation of molecular mechanisms underlying the antiproliferative effects of colchicine against PC3 prostate cancer cells. Toxicol In Vitro. 2021 Jun;73:105138. doi: 10.1016/j.tiv.2021.105138. Epub 2021 Mar 6.
• [70] Profiling the immunotoxicity of chemicals based on in vitro evaluation by a combination of the Multi-ImmunoTox assay and the IL-8 Luc assay. Arch Toxicol. 2018 Jun;92(6):2043-2054. doi: 10.1007/s00204-018-2199-7. Epub 2018 Mar 29.
• [71] Establishment of a 13 genes-based molecular prediction score model to discriminate the neurotoxic potential of food relevant-chemicals. Toxicol Lett. 2022 Feb 1;355:1-18. doi: 10.1016/j.toxlet.2021.10.013. Epub 2021 Nov 5.
• [72] Induced differentiation in HT29, a human colon adenocarcinoma cell line. J Cell Sci. 1999 Aug;112 ( Pt 16):2657-66. doi: 10.1242/jcs.112.16.2657.
• [73] Comparison of the mutagenic potential of 17 physical and chemical agents analyzed by the flow cytometry mutation assay. Mutat Res. 2006 Dec 1;602(1-2):14-25. doi: 10.1016/j.mrfmmm.2006.07.009. Epub 2006 Oct 11.
• [74] Microtubule disarray in primary cultures of human hepatocytes inhibits transcriptional activity of the glucocorticoid receptor via activation of c-jun N-terminal kinase. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2004 Dec;148(2):135-9.
• [75] High-content imaging-based BAC-GFP toxicity pathway reporters to assess chemical adversity liabilities. Arch Toxicol. 2017 Mar;91(3):1367-1383. doi: 10.1007/s00204-016-1781-0. Epub 2016 Jun 29.
• [76] Involvement of cytoskeleton in AhR-dependent CYP1A1 expression. Curr Drug Metab. 2006 Apr;7(3):301-13. doi: 10.2174/138920006776359310.
• [77] Zinc and the cytoskeleton in the neuronal modulation of transcription factor NFAT. J Cell Physiol. 2007 Jan;210(1):246-56. doi: 10.1002/jcp.20861.
• [78] Population-based in vitro hazard and concentration-response assessment of chemicals: the 1000 genomes high-throughput screening study. Environ Health Perspect. 2015 May;123(5):458-66. doi: 10.1289/ehp.1408775. Epub 2015 Jan 13.