Details of the Drug Combination

General Information of Drug Combination (ID: DCA1XJU)

• Drug Combination Name: GFT-505 + Indomethacin
• Indication: Drug-drug Interaction; Status: Phase 1 [1]
• Component Drugs:
  GFT-505 (DM7ZOAE): N.A.
  Indomethacin (DMSC4A7): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of GFT-505

Disease Entry	ICD 11	Status	REF
Non-alcoholic steatohepatitis	DB92.1	Phase 3	[2]
Type-2 diabetes	5A11	Phase 2	[3]

GFT-505 Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Peroxisome proliferator-activated receptor delta (PPARD)	TT2JWF6	PPARD_HUMAN	Modulator	[7]
Peroxisome proliferator-activated receptor alpha (PPARA)	TTJ584C	PPARA_HUMAN	Modulator	[7]

Indication(s) of Indomethacin

Disease Entry	ICD 11	Status	REF
Bursitis	N.A.	Approved	[4]
Gout	FA25	Approved	[4]
Osteoarthritis	FA00-FA05	Approved	[4]
Patent ductus arteriosus	N.A.	Approved	[4]
Rheumatic disorder	N.A.	Approved	[4]
Rheumatoid arthritis	FA20	Approved	[5]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 1/2	[6]
Synovitis	N.A.	Investigative	[4]

Indomethacin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Prostaglandin G/H synthase 2 (COX-2)	TTVKILB	PGH2_HUMAN	Modulator	[19]

Indomethacin Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[20]

Indomethacin Interacts with 5 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[21]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[21]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[21]
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Metabolism	[22]
UDP-glucuronosyltransferase 1A9 (UGT1A9)	DE85D2P	UD19_HUMAN	Metabolism	[22]

Indomethacin Interacts with 205 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Retinoblastoma-associated protein (RB1)	OTQJUJMZ	RB_HUMAN	Decreases Phosphorylation	[23]
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A)	OT2D9DOV	TNR1A_HUMAN	Increases ADR	[24]
Solute carrier family 22 member 2 (SLC22A2)	OTGFK1AL	S22A2_HUMAN	Decreases Activity	[25]
Solute carrier family 22 member 1 (SLC22A1)	OT7817I4	S22A1_HUMAN	Decreases Activity	[25]
Solute carrier family 22 member 6 (SLC22A6)	OTKRCBVM	S22A6_HUMAN	Decreases Activity	[25]
Organic anion transporter 7 (SLC22A9)	OTO4BJCC	S22A9_HUMAN	Decreases Activity	[25]
Solute carrier family 22 member 11 (SLC22A11)	OTAJLNJZ	S22AB_HUMAN	Decreases Activity	[25]
Solute carrier family 22 member 7 (SLC22A7)	OTKTNH1W	S22A7_HUMAN	Decreases Activity	[25]
Aldo-keto reductase family 1 member C4 (AKR1C4)	OTW2MMOF	AK1C4_HUMAN	Decreases Activity	[26]
Aldo-keto reductase family 1 member C2 (AKR1C2)	OTQ2XMO3	AK1C2_HUMAN	Decreases Activity	[26]
Aldo-keto reductase family 1 member C1 (AKR1C1)	OTQKR4CM	AK1C1_HUMAN	Decreases Activity	[26]
Diamine acetyltransferase 1 (SAT1)	OT52AU22	SAT1_HUMAN	Increases Expression	[27]
Importin-5 (IPO5)	OTAK40ED	IPO5_HUMAN	Decreases Expression	[11]
Transcription factor E2F3 (E2F3)	OT5VQMWY	E2F3_HUMAN	Decreases Expression	[11]
AT-rich interactive domain-containing protein 1A (ARID1A)	OTRWDV3P	ARI1A_HUMAN	Decreases Expression	[11]
Class E basic helix-loop-helix protein 40 (BHLHE40)	OTITX14U	BHE40_HUMAN	Increases Expression	[11]
Chromodomain-helicase-DNA-binding protein 1 (CHD1)	OT9R9G0H	CHD1_HUMAN	Decreases Expression	[11]
E3 ubiquitin-protein ligase Praja-2 (PJA2)	OT45TMC4	PJA2_HUMAN	Decreases Expression	[11]
Phospholipid-transporting ATPase IC (ATP8B1)	OTALGS63	AT8B1_HUMAN	Decreases Expression	[11]
Zinc finger protein SNAI2 (SNAI2)	OT7Y8EJ2	SNAI2_HUMAN	Increases Expression	[11]
NUAK family SNF1-like kinase 1 (NUAK1)	OTLLHJJQ	NUAK1_HUMAN	Increases Expression	[11]
cAMP-responsive element-binding protein-like 2 (CREBL2)	OT58JBNU	CRBL2_HUMAN	Decreases Expression	[11]
Thiamine transporter 1 (SLC19A2)	OTH5SB0M	S19A2_HUMAN	Increases Expression	[11]
DnaJ homolog subfamily A member 2 (DNAJA2)	OTKF1VBT	DNJA2_HUMAN	Decreases Expression	[11]
Frizzled-7 (FZD7)	OTTK3F6E	FZD7_HUMAN	Decreases Expression	[11]
Suppressor of cytokine signaling 5 (SOCS5)	OTN1ABYR	SOCS5_HUMAN	Decreases Expression	[11]
Growth arrest and DNA damage-inducible protein GADD45 beta (GADD45B)	OTL9I7LO	GA45B_HUMAN	Increases Expression	[11]
Glutaminase kidney isoform, mitochondrial (GLS)	OTGOZG2M	GLSK_HUMAN	Decreases Expression	[11]
Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4)	OTBMJUOC	M4K4_HUMAN	Decreases Expression	[11]
Plasminogen activator inhibitor 1 (SERPINE1)	OTT0MPQ3	PAI1_HUMAN	Increases Expression	[11]
Transcription factor Jun (JUN)	OTCYBO6X	JUN_HUMAN	Increases Expression	[11]
Tyrosine-protein kinase Lyn (LYN)	OTP686K2	LYN_HUMAN	Decreases Expression	[11]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Decreases Expression	[11]
RNA-binding protein RO60 (RO60)	OTLGM5A8	RO60_HUMAN	Decreases Expression	[11]
Transcription factor JunB (JUNB)	OTG2JXV5	JUNB_HUMAN	Increases Expression	[11]
Protein SON (SON)	OT9VWV18	SON_HUMAN	Decreases Expression	[11]
COUP transcription factor 2 (NR2F2)	OTJFS67N	COT2_HUMAN	Decreases Expression	[11]
Guanylate-binding protein 1 (GBP1)	OTUM7RPJ	GBP1_HUMAN	Decreases Expression	[11]
Transcription factor SOX-18 (SOX18)	OTPUMHWA	SOX18_HUMAN	Increases Expression	[11]
Interleukin-6 receptor subunit beta (IL6ST)	OT1N9C70	IL6RB_HUMAN	Decreases Expression	[11]
Cyclin-dependent kinase inhibitor 1B (CDKN1B)	OTNY5LLZ	CDN1B_HUMAN	Decreases Expression	[11]
Eukaryotic translation initiation factor 1A, X-chromosomal (EIF1AX)	OTWG2LAB	IF1AX_HUMAN	Decreases Expression	[11]
Protein Tob1 (TOB1)	OTNW949D	TOB1_HUMAN	Decreases Expression	[11]
UV excision repair protein RAD23 homolog B (RAD23B)	OT0PGOG3	RD23B_HUMAN	Decreases Expression	[11]
ATP synthase subunit e, mitochondrial (ATP5ME)	OTADVEE2	ATP5I_HUMAN	Increases Expression	[11]
ADP-ribosylation factor-like protein 4C (ARL4C)	OTQ3QNNU	ARL4C_HUMAN	Decreases Expression	[11]
Protein BTG1 (BTG1)	OTVJ2CDM	BTG1_HUMAN	Increases Expression	[11]
Rho-related GTP-binding protein RhoB (RHOB)	OTHQFQF7	RHOB_HUMAN	Increases Expression	[11]
Dystonin (DST)	OTHZBM4X	DYST_HUMAN	Decreases Expression	[11]
Tyrosine-protein phosphatase non-receptor type 12 (PTPN12)	OT5WA666	PTN12_HUMAN	Decreases Expression	[11]
Serine/arginine-rich splicing factor 6 (SRSF6)	OTGLOSYE	SRSF6_HUMAN	Decreases Expression	[11]
Baculoviral IAP repeat-containing protein 3 (BIRC3)	OT3E95KB	BIRC3_HUMAN	Decreases Expression	[11]
Serine/threonine-protein kinase PRP4 homolog (PRP4K)	OT4C7XNK	PRP4B_HUMAN	Decreases Expression	[11]
G/T mismatch-specific thymine DNA glycosylase (TDG)	OTJB0YIH	TDG_HUMAN	Decreases Expression	[11]
Protein EFR3 homolog A (EFR3A)	OTVHT160	EFR3A_HUMAN	Decreases Expression	[11]
AT-rich interactive domain-containing protein 5B (ARID5B)	OTUQ4CQY	ARI5B_HUMAN	Decreases Expression	[11]
TSC22 domain family protein 1 (TSC22D1)	OTN4GFWD	T22D1_HUMAN	Increases Expression	[11]
Cyclin-G2 (CCNG2)	OTII38K2	CCNG2_HUMAN	Increases Expression	[11]
Cleavage and polyadenylation specificity factor subunit 6 (CPSF6)	OTM6QYNQ	CPSF6_HUMAN	Decreases Expression	[11]
Dual specificity protein phosphatase 6 (DUSP6)	OT4H6RKW	DUS6_HUMAN	Decreases Expression	[11]
Tumor protein D53 (TPD52L1)	OTSA6U0I	TPD53_HUMAN	Decreases Expression	[11]
Centrosome and spindle pole-associated protein 1 (CSPP1)	OTNX7GD4	CSPP1_HUMAN	Decreases Expression	[11]
Protein LBH (LBH)	OT87AT1X	LBH_HUMAN	Increases Expression	[11]
NHS-like protein 1 (NHSL1)	OTLEZ2C3	NHSL1_HUMAN	Decreases Expression	[11]
Putative uncharacterized protein C6orf52 (C6ORF52)	OTDW07T3	CF052_HUMAN	Increases Expression	[11]
PX domain-containing protein 1 (PXDC1)	OTQUA3TG	PXDC1_HUMAN	Increases Expression	[11]
Zinc finger protein AEBP2 (AEBP2)	OTOAZJ55	AEBP2_HUMAN	Decreases Expression	[11]
Ras-associated and pleckstrin homology domains-containing protein 1 (RAPH1)	OTMQXW7S	RAPH1_HUMAN	Decreases Expression	[11]
FMR1-interacting protein NUFIP2 (NUFIP2)	OTZBZ224	NUFP2_HUMAN	Decreases Expression	[11]
E3 ubiquitin-protein ligase RNF144B (RNF144B)	OTN7FCDE	R144B_HUMAN	Decreases Expression	[11]
Neuroepithelial cell-transforming gene 1 protein (NET1)	OTZHNMJV	ARHG8_HUMAN	Increases Expression	[11]
Amphoterin-induced protein 2 (AMIGO2)	OTPAIT1O	AMGO2_HUMAN	Increases Expression	[11]
Histone-arginine methyltransferase METTL23 (METTL23)	OTO7O557	MET23_HUMAN	Increases Expression	[11]
Protein O-mannosyl-transferase TMTC1 (TMTC1)	OTZ7NW96	TMTC1_HUMAN	Decreases Expression	[11]
Coiled-coil domain-containing protein 50 (CCDC50)	OTSE1YM5	CCD50_HUMAN	Increases Expression	[11]
E3 ubiquitin-protein ligase HACE1 (HACE1)	OTEZULKD	HACE1_HUMAN	Decreases Expression	[11]
Ankyrin repeat domain-containing protein 13C (ANKRD13C)	OT8LJ550	AN13C_HUMAN	Decreases Expression	[11]
Hemicentin-2 (HMCN2)	OTJK9CGG	HMCN2_HUMAN	Increases Expression	[11]
Acrosin-binding protein (ACRBP)	OT0MK3L1	ACRBP_HUMAN	Increases Expression	[11]
Mitochondria-eating protein (SPATA18)	OTOEHTHU	MIEAP_HUMAN	Decreases Expression	[11]
Pantothenate kinase 1 (PANK1)	OT2CZVRT	PANK1_HUMAN	Decreases Expression	[11]
Rap guanine nucleotide exchange factor 6 (RAPGEF6)	OTR1QQA3	RPGF6_HUMAN	Decreases Expression	[11]
Neuronal cell adhesion molecule (NRCAM)	OT80HHQ2	NRCAM_HUMAN	Decreases Expression	[11]
Transcription factor GATA-6 (GATA6)	OTO2BC0F	GATA6_HUMAN	Increases Expression	[11]
Protein TMEPAI (PMEPA1)	OTY8Z9UF	PMEPA_HUMAN	Increases Expression	[11]
Arrestin domain-containing protein 3 (ARRDC3)	OTAKW7R9	ARRD3_HUMAN	Increases Expression	[11]
BTB/POZ domain-containing protein KCTD12 (KCTD12)	OTPYKT4Z	KCD12_HUMAN	Decreases Expression	[11]
RING finger protein 145 (RNF145)	OTBCTG4A	RN145_HUMAN	Decreases Expression	[11]
Transmembrane protein 237 (TMEM237)	OTQEVL7L	TM237_HUMAN	Decreases Expression	[11]
Trimethylguanosine synthase (TGS1)	OTM79LML	TGS1_HUMAN	Decreases Expression	[11]
RNA-binding protein 15 (RBM15)	OT8ZPGWF	RBM15_HUMAN	Decreases Expression	[11]
Plakophilin-4 (PKP4)	OTQHOF8L	PKP4_HUMAN	Decreases Expression	[11]
Cbp/p300-interacting transactivator 2 (CITED2)	OT812TV7	CITE2_HUMAN	Decreases Expression	[11]
Transcription factor SOX-7 (SOX7)	OTOZOFAG	SOX7_HUMAN	Decreases Expression	[11]
Death-inducer obliterator 1 (DIDO1)	OT9PB547	DIDO1_HUMAN	Decreases Expression	[11]
Activity-dependent neuroprotector homeobox protein (ADNP)	OTEGICWR	ADNP_HUMAN	Decreases Expression	[11]
Interferon-stimulated 20 kDa exonuclease-like 2 (ISG20L2)	OT3Q11WQ	I20L2_HUMAN	Decreases Expression	[11]
Retroelement silencing factor 1 (RESF1)	OTQIZIJF	RESF1_HUMAN	Decreases Expression	[11]
DnaJ homolog subfamily C member 4 (DNAJC4)	OT4BUBQU	DNJC4_HUMAN	Increases Expression	[11]
Muscleblind-like protein 1 (MBNL1)	OTOV7J85	MBNL1_HUMAN	Decreases Expression	[11]
Bromodomain adjacent to zinc finger domain protein 1A (BAZ1A)	OTWHOVZS	BAZ1A_HUMAN	Decreases Expression	[11]
Sperm protein associated with the nucleus on the X chromosome A (SPANXA1)	OTMK3QIS	SPNXA_HUMAN	Increases Expression	[11]
Sal-like protein 1 (SALL1)	OTYYZGLH	SALL1_HUMAN	Increases Expression	[11]
Serine/threonine-protein phosphatase 4 regulatory subunit 2 (PPP4R2)	OT7FCZRM	PP4R2_HUMAN	Decreases Expression	[11]
Serine/threonine-protein kinase PLK2 (PLK2)	OTKMJXJ8	PLK2_HUMAN	Decreases Expression	[11]
]-phosphatase 1, mitochondrial (PDP1)	OT82RTMT	PDP1_HUMAN	Decreases Expression	[11]
DNA repair protein REV1 (REV1)	OTHIKICX	REV1_HUMAN	Decreases Expression	[11]
Translocation protein SEC63 homolog (SEC63)	OT1ICPMK	SEC63_HUMAN	Decreases Expression	[11]
A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1)	OTTLJH8W	ATS1_HUMAN	Decreases Expression	[11]
Tomoregulin-2 (TMEFF2)	OT1WZ2QO	TEFF2_HUMAN	Decreases Expression	[11]
F-box/WD repeat-containing protein 2 (FBXW2)	OTCHPUCP	FBXW2_HUMAN	Decreases Expression	[11]
Scrapie-responsive protein 1 (SCRG1)	OTBE7V0P	SCRG1_HUMAN	Increases Expression	[12]
Amino acid transporter heavy chain SLC3A2 (SLC3A2)	OTBR33M9	4F2_HUMAN	Increases Expression	[12]
Serine--tRNA ligase, cytoplasmic (SARS1)	OTFKXQ1O	SYSC_HUMAN	Increases Expression	[12]
Phosphoserine phosphatase (PSPH)	OTV1PVAX	SERB_HUMAN	Increases Expression	[12]
Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1)	OTXEE550	APR_HUMAN	Increases Expression	[12]
Mitochondrial 10-formyltetrahydrofolate dehydrogenase (ALDH1L2)	OTCH86VF	AL1L2_HUMAN	Increases Expression	[12]
Spermatogenesis-associated serine-rich protein 1 (SPATS1)	OTPUXCSA	SPAS1_HUMAN	Decreases Expression	[12]
Tribbles homolog 3 (TRIB3)	OTG5OS7X	TRIB3_HUMAN	Increases Expression	[12]
Glutathione-specific gamma-glutamylcyclotransferase 1 (CHAC1)	OTJGE772	CHAC1_HUMAN	Increases Expression	[12]
Protein DEPP1 (DEPP1)	OTB36PHJ	DEPP1_HUMAN	Decreases Expression	[12]
Cell cycle progression protein 1 (CCPG1)	OT0IHDKL	CCPG1_HUMAN	Increases Expression	[12]
Adenosine receptor A3 (ADORA3)	OTHO1BLK	AA3R_HUMAN	Increases Expression	[28]
5'-nucleotidase (NT5E)	OT7J5LT6	5NTD_HUMAN	Increases Expression	[28]
Aldo-keto reductase family 1 member C3 (AKR1C3)	OTU2SXBA	AK1C3_HUMAN	Decreases Activity	[29]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[30]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[31]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[31]
Leukocyte cell-derived chemotaxin 1 (CNMD)	OTHND8EL	CNMD_HUMAN	Increases Expression	[14]
ABC-type organic anion transporter ABCA8 (ABCA8)	OTCWLX6N	ABCA8_HUMAN	Increases Expression	[14]
RAS guanyl-releasing protein 1 (RASGRP1)	OTX9WN2E	GRP1_HUMAN	Increases Expression	[14]
C-X-C motif chemokine 14 (CXCL14)	OTM189TA	CXL14_HUMAN	Increases Expression	[14]
Collagen alpha-1(II) chain (COL2A1)	OT5E59C8	CO2A1_HUMAN	Decreases Expression	[14]
Homeobox protein Hox-D4 (HOXD4)	OTQR4WCG	HXD4_HUMAN	Decreases Expression	[14]
Homeobox protein Hox-D3 (HOXD3)	OTBUZ35T	HXD3_HUMAN	Decreases Expression	[14]
Metalloproteinase inhibitor 3 (TIMP3)	OTDGQAD1	TIMP3_HUMAN	Increases Expression	[14]
Nuclear receptor subfamily 4 group A member 2 (NR4A2)	OT3F9IR2	NR4A2_HUMAN	Decreases Expression	[14]
LIM/homeobox protein Lhx1 (LHX1)	OT6WI2XS	LHX1_HUMAN	Decreases Expression	[14]
Ras association domain-containing protein 2 (RASSF2)	OT2JHDO4	RASF2_HUMAN	Increases Expression	[14]
Paired mesoderm homeobox protein 1 (PRRX1)	OTTZK5G8	PRRX1_HUMAN	Decreases Expression	[14]
Myosin light chain kinase, smooth muscle (MYLK)	OT78QB4A	MYLK_HUMAN	Increases Expression	[14]
Growth/differentiation factor 6 (GDF6)	OTERXWJU	GDF6_HUMAN	Increases Expression	[14]
Rhomboid-related protein 4 (RHBDD1)	OTL5J132	RHBL4_HUMAN	Increases Expression	[14]
SOSS complex subunit B2 (NABP1)	OTFTNFHW	SOSB2_HUMAN	Increases Expression	[14]
Ribosomal protein eL39-like 2 (RPL39L)	OTAV1MJQ	RL39L_HUMAN	Increases Expression	[14]
Homeobox protein Hox-D1 (HOXD1)	OTN4V9ZF	HXD1_HUMAN	Decreases Expression	[14]
Band 4.1-like protein 4B (EPB41L4B)	OT2K30P7	E41LB_HUMAN	Increases Expression	[14]
Regulator of cell cycle RGCC (RGCC)	OTYJMLWM	RGCC_HUMAN	Increases Expression	[14]
Homeobox protein NANOG (NANOG)	OTUEY1FM	NANOG_HUMAN	Decreases Expression	[14]
Armadillo repeat-containing X-linked protein 1 (ARMCX1)	OTOGL58Z	ARMX1_HUMAN	Decreases Expression	[14]
Nuclear factor erythroid 2-related factor 3 (NFE2L3)	OT1MGXT0	NF2L3_HUMAN	Increases Expression	[14]
Calpain-6 (CAPN6)	OT8K5PR5	CAN6_HUMAN	Increases Expression	[14]
Stearoyl-CoA desaturase (SCD)	OTB1073G	SCD_HUMAN	Increases Expression	[32]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[33]
ATP-binding cassette sub-family C member 3 (ABCC3)	OTC3IJV4	MRP3_HUMAN	Increases Expression	[34]
Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1)	OTY9R6FZ	ERN1_HUMAN	Increases Expression	[32]
Tumor necrosis factor receptor superfamily member 21 (TNFRSF21)	OT3EDGXO	TNR21_HUMAN	Decreases Expression	[35]
ATP-binding cassette sub-family C member 6 (ABCC6)	OTZT0LKT	MRP6_HUMAN	Decreases Activity	[36]
CCN family member 4 (CCN4)	OT69BER9	CCN4_HUMAN	Decreases Expression	[37]
Renin (REN)	OT52GZR2	RENI_HUMAN	Decreases Activity	[38]
Metalloproteinase inhibitor 1 (TIMP1)	OTOXC51H	TIMP1_HUMAN	Increases Expression	[39]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Increases Expression	[40]
Natriuretic peptides A (NPPA)	OTMQNTNX	ANF_HUMAN	Decreases Expression	[41]
Vasopressin-neurophysin 2-copeptin (AVP)	OTAVZ76K	NEU2_HUMAN	Decreases Secretion	[42]
Amyloid-beta precursor protein (APP)	OTKFD7R4	A4_HUMAN	Affects Cleavage	[43]
Protein disulfide-isomerase (P4HB)	OTTYNYPF	PDIA1_HUMAN	Decreases Expression	[32]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[44]
Laminin subunit gamma-1 (LAMC1)	OTIG527N	LAMC1_HUMAN	Decreases Expression	[45]
Heat shock cognate 71 kDa protein (HSPA8)	OTJI2RCI	HSP7C_HUMAN	Affects Localization	[46]
Cadherin-1 (CDH1)	OTFJMXPM	CADH1_HUMAN	Increases Expression	[47]
Fatty acid-binding protein, adipocyte (FABP4)	OT3DKFOU	FABP4_HUMAN	Increases Expression	[48]
15-hydroxyprostaglandin dehydrogenase (HPGD)	OTYZI6JB	PGDH_HUMAN	Increases Expression	[49]
Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6)	OTAFHAVI	ATF6A_HUMAN	Increases Expression	[32]
Nuclear factor NF-kappa-B p105 subunit (NFKB1)	OTNRRD8I	NFKB1_HUMAN	Decreases Expression	[50]
Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1)	OTGP6GA4	NR4A1_HUMAN	Increases Expression	[51]
Protein kinase C eta type (PRKCH)	OTC498N5	KPCL_HUMAN	Increases Expression	[52]
Adenomatous polyposis coli protein (APC)	OTKV0TIK	APC_HUMAN	Increases Expression	[47]
G1/S-specific cyclin-D2 (CCND2)	OTDULQF9	CCND2_HUMAN	Decreases Expression	[53]
Catenin beta-1 (CTNNB1)	OTZ932A3	CTNB1_HUMAN	Decreases Expression	[54]
DNA damage-inducible transcript 3 protein (DDIT3)	OTI8YKKE	DDIT3_HUMAN	Increases Expression	[32]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Activity	[55]
Dual specificity mitogen-activated protein kinase kinase 4 (MAP2K4)	OTZPZX11	MP2K4_HUMAN	Increases Expression	[56]
Microsomal triglyceride transfer protein large subunit (MTTP)	OTNUVSDT	MTP_HUMAN	Decreases Expression	[32]
BH3-interacting domain death agonist (BID)	OTOSHSHU	BID_HUMAN	Increases Cleavage	[57]
Cytochrome c (CYCS)	OTBFALJD	CYC_HUMAN	Affects Localization	[58]
Heat shock factor protein 1 (HSF1)	OTYNJ4KP	HSF1_HUMAN	Increases Activity	[59]
Cytochrome P450 4A11 (CYP4A11)	OTPU5J0S	CP4AB_HUMAN	Affects Activity	[60]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Affects Localization	[61]
Tight junction protein ZO-1 (TJP1)	OTBDCUPK	ZO1_HUMAN	Decreases Expression	[62]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[63]
Acetyl-CoA carboxylase 1 (ACACA)	OT5CQPZY	ACACA_HUMAN	Increases Expression	[32]
Transcription factor HES-1 (HES1)	OT8P19W2	HES1_HUMAN	Decreases Expression	[64]
Bcl-2 homologous antagonist/killer (BAK1)	OTDP6ILW	BAK_HUMAN	Increases Expression	[44]
Occludin (OCLN)	OTSUTVWL	OCLN_HUMAN	Decreases Expression	[62]
Dehydrogenase/reductase SDR family member 11 (DHRS11)	OTU3J0ZL	DHR11_HUMAN	Decreases Activity	[65]
Bcl2-associated agonist of cell death (BAD)	OT63ERYM	BAD_HUMAN	Increases Expression	[64]
Bcl-2-binding component 3, isoforms 3/4 (BBC3)	OTUAXDAY	BBC3B_HUMAN	Increases Expression	[64]
Perilipin-2 (PLIN2)	OTRXJ9UN	PLIN2_HUMAN	Increases Expression	[66]
Phospholipid-transporting ATPase ABCA3 (ABCA3)	OTH6MSKQ	ABCA3_HUMAN	Decreases Expression	[67]
Eukaryotic translation initiation factor 2-alpha kinase 3 (EIF2AK3)	OT0DZGY4	E2AK3_HUMAN	Increases Expression	[32]
Cytochrome b5 (CYB5A)	OT6SN4RM	CYB5_HUMAN	Increases ADR	[24]
Heat shock 70 kDa protein 12A (HSPA12A)	OTFOCDD6	HS12A_HUMAN	Increases ADR	[24]
p21 protein (HRAS)	OTFYE6AJ	P78460_HUMAN	Increases ADR	[24]
Transcriptional activator Myb (MYB)	OTJH64IV	MYB_HUMAN	Increases ADR	[24]
NADH-cytochrome b5 reductase 3 (CYB5R3)	OTUGT3G8	NB5R3_HUMAN	Increases ADR	[24]

References

• [1] ClinicalTrials.gov (NCT03985969) Study to Investigate the Potential Drug-Drug Interaction Between Elafibranor and Indomethacin
• [2] ClinicalTrials.gov (NCT02704403) Phase 3 Study to Evaluate the Efficacy and Safety of Elafibranor Versus Placebo in Patients With Nonalcoholic Steatohepatitis (NASH) (RESOLVE-IT). U.S. National Institutes of Health.
• [3] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025107)
• [4] Indomethacin FDA Label
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [6] ClinicalTrials.gov (NCT04344457) Evaluate the Efficacy and Safety of Oral Hydroxychloroquine, Indomethacin and Zithromax in Subjects With Mild Symptoms of COVID-19. U.S. National Institutes of Health.
• [7] Dual peroxisome proliferator-activated receptor / agonist GFT505 improves hepatic and peripheral insulin sensitivity in abdominally obese subjects.Diabetes Care.2013 Oct;36(10):2923-30.
• [8] In vitro inhibitory effects of non-steroidal antiinflammatory drugs on UDP-glucuronosyltransferase 1A1-catalysed estradiol 3beta-glucuronidation in human liver microsomes. Biopharm Drug Dispos. 2005 Jan;26(1):35-9.
• [9] Glucuronidation of nonsteroidal anti-inflammatory drugs: identifying the enzymes responsible in human liver microsomes. Drug Metab Dispos. 2005 Jul;33(7):1027-35.
• [10] Complementary deoxyribonucleic acid cloning and expression of a human liver uridine diphosphate-glucuronosyltransferase glucuronidating carboxylic acid-containing drugs. J Pharmacol Exp Ther. 1993 Jan;264(1):475-9.
• [11] Mechanisms of indomethacin-induced alterations in the choline phospholipid metabolism of breast cancer cells. Neoplasia. 2006 Sep;8(9):758-71.
• [12] Anti-inflammatory agent indomethacin reduces invasion and alters metabolism in a human breast cancer cell line. Neoplasia. 2007 Mar;9(3):222-35.
• [13] Activation of phospholipase A2 is involved in indomethacin-induced damage in Caco-2 cells. Toxicol In Vitro. 2009 Aug;23(5):887-96.
• [14] Evaluation of developmental toxicity using undifferentiated human embryonic stem cells. J Appl Toxicol. 2015 Feb;35(2):205-18.
• [15] Indomethacin suppresses growth of colon cancer via inhibition of angiogenesis in vivo. World J Gastroenterol. 2005 Jan 21;11(3):340-3. doi: 10.3748/wjg.v11.i3.340.
• [16] Nonsteroidal anti-inflammatory drugs induce colorectal cancer cell apoptosis by suppressing 14-3-3epsilon. Cancer Res. 2007 Apr 1;67(7):3185-91. doi: 10.1158/0008-5472.CAN-06-3431.
• [17] Highly variable pH effects on the interaction of diclofenac and indomethacin with human UDP-glucuronosyltransferases. Toxicol In Vitro. 2012 Dec;26(8):1286-93. doi: 10.1016/j.tiv.2012.01.005. Epub 2012 Jan 14.
• [18] Gastrointestinally distributed UDP-glucuronosyltransferase 1A10, which metabolizes estrogens and nonsteroidal anti-inflammatory drugs, depends upon phosphorylation. J Biol Chem. 2004 Jul 2;279(27):28320-9. doi: 10.1074/jbc.M401396200. Epub 2004 Apr 26.
• [19] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [20] Indomethacin induces apoptosis via a MRP1-dependent mechanism in doxorubicin-resistant small-cell lung cancer cells overexpressing MRP1. Br J Cancer. 2007 Oct 22;97(8):1077-83.
• [21] 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.
• [22] Contribution of UDP-glucuronosyltransferases 1A9 and 2B7 to the glucuronidation of indomethacin in the human liver. Eur J Clin Pharmacol. 2007 Mar;63(3):289-96.
• [23] Indomethacin inhibits cell growth of medullary thyroid carcinoma by reducing cell cycle progression into S phase. Exp Biol Med (Maywood). 2008 Nov;233(11):1433-40. doi: 10.3181/0804-RM-127. Epub 2008 Sep 12.
• [24] 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.
• [25] Interactions of human organic anion transporters and human organic cation transporters with nonsteroidal anti-inflammatory drugs. J Pharmacol Exp Ther. 2002 Nov;303(2):534-9.
• [26] Selective and potent inhibitors of human 20alpha-hydroxysteroid dehydrogenase (AKR1C1) that metabolizes neurosteroids derived from progesterone. Chem Biol Interact. 2003 Feb 1;143-144:503-13.
• [27] Induction of spermidine/spermine N1-acetyltransferase (SSAT) by aspirin in Caco-2 colon cancer cells. Biochem J. 2006 Feb 15;394(Pt 1):317-24.
• [28] Indomethacin stimulates activity and expression of ecto-5'-nucleotidase/CD73 in glioma cell lines. Eur J Pharmacol. 2007 Aug 13;569(1-2):8-15.
• [29] An indomethacin analogue, N-(4-chlorobenzoyl)-melatonin, is a selective inhibitor of aldo-keto reductase 1C3 (type 2 3alpha-HSD, type 5 17beta-HSD, and prostaglandin F synthase), a potential target for the treatment of hormone dependent and hormone independent malignancies. Biochem Pharmacol. 2008 Jan 15;75(2):484-93.
• [30] 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.
• [31] Indomethacin-enhanced anticancer effect of arsenic trioxide in A549 cell line: involvement of apoptosis and phospho-ERK and p38 MAPK pathways. Biomed Res Int. 2013;2013:237543.
• [32] Drug-induced hepatic steatosis in absence of severe mitochondrial dysfunction in HepaRG cells: proof of multiple mechanism-based toxicity. Cell Biol Toxicol. 2021 Apr;37(2):151-175. doi: 10.1007/s10565-020-09537-1. Epub 2020 Jun 14.
• [33] [Indomethacin induces apoptosis through inhibition of survivin regulated by beta-catenin/TCF4 in human colorectal cancer cells]. Ai Zheng. 2004 Jul;23(7):737-41.
• [34] Induction of multidrug resistance proteins MRP1 and MRP3 and gamma-glutamylcysteine synthetase gene expression by nonsteroidal anti-inflammatory drugs in human colon cancer cells. Biochem Biophys Res Commun. 2002 Feb 8;290(5):1427-33. doi: 10.1006/bbrc.2002.6367.
• [35] Tumor necrosis factor-alpha induces the expression of DR6, a member of the TNF receptor family, through activation of NF-kappaB. Oncogene. 2001 Nov 29;20(55):7965-75. doi: 10.1038/sj.onc.1204985.
• [36] Multidrug resistance protein-6 (MRP6) in human dermal fibroblasts. Comparison between cells from normal subjects and from Pseudoxanthoma elasticum patients. Matrix Biol. 2003 Nov;22(6):491-500. doi: 10.1016/j.matbio.2003.09.001.
• [37] Effect of indomethacin on Bfl-1, WISP-1 and proliferating cell nuclear antigen in colon cancer cell line HCT116 cells. Chin J Dig Dis. 2006;7(4):219-24. doi: 10.1111/j.1443-9573.2006.00272.x.
• [38] Acute renal effects of sulindac and indomethacin in chronic renal failure. Clin Pharmacol Ther. 1985 Apr;37(4):447-52. doi: 10.1038/clpt.1985.69.
• [39] Matrix metalloproteinase (MMP)-2 and MMP-9 and their inhibitor, TIMP-1, in human term decidua and fetal membranes: the effect of prostaglandin F(2alpha) and indomethacin. Mol Hum Reprod. 2001 Dec;7(12):1187-93. doi: 10.1093/molehr/7.12.1187.
• [40] Differential apoptosis by indomethacin in gastric epithelial cells through the constitutive expression of wild-type p53 and/or up-regulation of c-myc. Biochem Pharmacol. 1999 Jul 1;58(1):193-200. doi: 10.1016/s0006-2952(99)00058-1.
• [41] Atrial natriuretic peptide in the diagnosis of patent ductus arteriosus. Acta Paediatr. 1992 Sep;81(9):672-5. doi: 10.1111/j.1651-2227.1992.tb12330.x.
• [42] Urinary ET-1, AVP and sodium in premature infants treated with indomethacin and ibuprofen for patent ductus arteriosus. Pediatr Nephrol. 2005 Nov;20(11):1552-6. doi: 10.1007/s00467-005-2022-6. Epub 2005 Aug 17.
• [43] A subset of NSAIDs lower amyloidogenic Abeta42 independently of cyclooxygenase activity. Nature. 2001 Nov 8;414(6860):212-6. doi: 10.1038/35102591.
• [44] Non-steroidal anti-inflammatory drugs induce apoptosis in gastric cancer cells through up-regulation of bax and bak. Carcinogenesis. 2001 Sep;22(9):1393-7. doi: 10.1093/carcin/22.9.1393.
• [45] The cyclooxygenase inhibitor indomethacin modulates gene expression and represses the extracellular matrix protein laminin gamma1 in human glioblastoma cells. Exp Cell Res. 2005 Jan 15;302(2):244-52. doi: 10.1016/j.yexcr.2004.09.021.
• [46] Indomethacin and ibuprofen induce Hsc70 nuclear localization and activation of the heat shock response in HeLa cells. Biochem Biophys Res Commun. 2004 Jan 23;313(4):863-70. doi: 10.1016/j.bbrc.2003.12.018.
• [47] Effect of indomethacin on E-cadherin and beta-catenin expression in HT-29 colon cancer cells. Exp Mol Pathol. 2006 Feb;80(1):91-6. doi: 10.1016/j.yexmp.2005.04.008. Epub 2005 Jun 16.
• [48] Human adipocyte fatty acid-binding protein (aP2) gene promoter-driven reporter assay discriminates nonlipogenic peroxisome proliferator-activated receptor gamma ligands. J Pharmacol Exp Ther. 2004 Nov;311(2):467-75. doi: 10.1124/jpet.104.068254. Epub 2004 Jul 23.
• [49] 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is up-regulated by flurbiprofen and other non-steroidal anti-inflammatory drugs in human colon cancer HT29 cells. Arch Biochem Biophys. 2009 Jul 15;487(2):139-45. doi: 10.1016/j.abb.2009.05.017. Epub 2009 Jun 6.
• [50] Development of an alternative zebrafish model for drug-induced intestinal toxicity. J Appl Toxicol. 2018 Feb;38(2):259-273. doi: 10.1002/jat.3520. Epub 2017 Oct 13.
• [51] Transcriptional induction of Nur77 by indomethacin that results in apoptosis of colon cancer cells. Biol Pharm Bull. 2000 Jul;23(7):815-9. doi: 10.1248/bpb.23.815.
• [52] Overexpression of protein kinase C-beta1 isoenzyme suppresses indomethacin-induced apoptosis in gastric epithelial cells. Gastroenterology. 2000 Mar;118(3):507-14. doi: 10.1016/s0016-5085(00)70256-3.
• [53] Anti-inflammatory drugs suppress proliferation and induce apoptosis through altering expressions of cell cycle regulators and pro-apoptotic factors in cultured human osteoblasts. Toxicology. 2009 Apr 28;258(2-3):148-56. doi: 10.1016/j.tox.2009.01.016. Epub 2009 Jan 22.
• [54] Indomethacin induces differential expression of beta-catenin, gamma-catenin and T-cell factor target genes in human colorectal cancer cells. Carcinogenesis. 2002 Jan;23(1):107-14. doi: 10.1093/carcin/23.1.107.
• [55] Nonsteroidal anti-inflammatory drugs inhibit growth of human neuroendocrine tumor cells via G1 cell-cycle arrest. Int J Cancer. 2003 Dec 10;107(5):844-53. doi: 10.1002/ijc.11446.
• [56] [Indomethacin-induced HL-60 leukemic cell apoptosis and the activation of C-jun NH2- terminal kinase signal transduction pathway]. Hunan Yi Ke Da Xue Xue Bao. 2003 Dec;28(6):557-62.
• [57] Indomethacin-induced activation of the death receptor-mediated apoptosis pathway circumvents acquired doxorubicin resistance in SCLC cells. Br J Cancer. 2005 Apr 25;92(8):1459-66. doi: 10.1038/sj.bjc.6602516.
• [58] Indomethacin-induced apoptosis in esophageal adenocarcinoma cells involves upregulation of Bax and translocation of mitochondrial cytochrome C independent of COX-2 expression. Neoplasia. 2000 Jul-Aug;2(4):346-56. doi: 10.1038/sj.neo.7900097.
• [59] Enhanced protein denaturation in indomethacin-treated cells. Cell Stress Chaperones. 2000 Jan;5(1):8-13. doi: 10.1043/1355-8145(2000)005<0008:EPDIIT>2.0.CO;2.
• [60] Effects of acidic non-steroidal anti-inflammatory drugs on human cytochrome P450 4A11 activity: Roles of carboxylic acid and a sulfur atom in potent inhibition by sulindac sulfide. Chem Biol Interact. 2023 Sep 1;382:110644. doi: 10.1016/j.cbi.2023.110644. Epub 2023 Jul 25.
• [61] The proapoptotic effects of sulindac, sulindac sulfone and indomethacin are mediated by nucleolar translocation of the RelA(p65) subunit of NF-kappaB. Oncogene. 2008 Apr 17;27(18):2648-55. doi: 10.1038/sj.onc.1210891. Epub 2007 Dec 3.
• [62] Polyphenols protect the epithelial barrier function of Caco-2 cells exposed to indomethacin through the modulation of occludin and zonula occludens-1 expression. J Agric Food Chem. 2013 Jun 5;61(22):5291-7. doi: 10.1021/jf400150p. Epub 2013 May 23.
• [63] Role of BAX in the apoptotic response to anticancer agents. Science. 2000 Nov 3;290(5493):989-92. doi: 10.1126/science.290.5493.989.
• [64] Indomethacin and juglone inhibit inflammatory molecules to induce apoptosis in colon cancer cells. J Biochem Mol Toxicol. 2020 Feb;34(2):e22433. doi: 10.1002/jbt.22433. Epub 2020 Jan 9.
• [65] Rabbit dehydrogenase/reductase SDR family member 11 (DHRS11): Its identity with acetohexamide reductase with broad substrate specificity and inhibitor sensitivity, different from human DHRS11. Chem Biol Interact. 2019 May 25;305:12-20. doi: 10.1016/j.cbi.2019.03.026. Epub 2019 Mar 26.
• [66] Regulation of peroxisome proliferator-activated receptor-beta/delta by the APC/beta-CATENIN pathway and nonsteroidal antiinflammatory drugs. Mol Carcinog. 2009 Oct;48(10):942-52. doi: 10.1002/mc.20546.
• [67] Alleviation of the drug-resistant phenotype in idarubicin and cytosine arabinoside double-resistant acute myeloid leukemia cells by indomethacin. Int J Oncol. 2008 Apr;32(4):931-6.