Details of the Drug Combination

General Information of Drug Combination (ID: DCEGATO)

• Drug Combination Name: Prednisolone + Hydroxychloroquine
• Indication: Lupus Nephritis; Status: Phase 1 [1]
• Component Drugs:
  Prednisolone (DMQ8FR2): Small molecular drug
  Hydroxychloroquine (DMSIVND): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Prednisolone

Disease Entry	ICD 11	Status	REF
Acute adrenal insufficiency	N.A.	Approved	[2]
Acute asthma	CA23	Approved	[2]
Addison disease	5A74.0	Approved	[2]
Allergic rhinitis	CA08.0	Approved	[2]
Angioedema	4A00.15	Approved	[2]
Aspiration pneumonitis	N.A.	Approved	[2]
Autoimmune haemolytic anaemia	3A20	Approved	[2]
Blepharoconjunctivitis	N.A.	Approved	[2]
Bursitis	N.A.	Approved	[2]
Cerebral edema	8D60.1	Approved	[2]
Chronic graft versus host disease	N.A.	Approved	[2]
Congenital adrenal hyperplasia	5A71.01	Approved	[2]
Corneal abrasion	NA06.4	Approved	[2]
Corneal ulcer	9A76	Approved	[2]
Crohn disease	DD70	Approved	[2]
Dacryocystitis	N.A.	Approved	[2]
Demodex blepharitis	1G07	Approved	[2]
Dermatitis herpetiformis	EB44	Approved	[2]
Diamond-Blackfan anemia	N.A.	Approved	[2]
Disorder of orbital region	N.A.	Approved	[2]
Epicondylitis	N.A.	Approved	[2]
Erythema multiforme	N.A.	Approved	[2]
Exanthem	N.A.	Approved	[2]
Fever	MG26	Approved	[2]
Granuloma annulare	N.A.	Approved	[2]
Hypersensitivity pneumonitis	N.A.	Approved	[2]
Inflammatory bowel disease	DD72	Approved	[2]
Ischemia-reperfusion injury	DB98.B	Approved	[2]
Keratitis	N.A.	Approved	[2]
Leukemia	N.A.	Approved	[2]
Lupus nephritis	4A40.0Y	Approved	[2]
Microscopic polyangiitis	N.A.	Approved	[2]
Miliary tuberculosis	N.A.	Approved	[2]
Mycosis fungoides	2B01	Approved	[2]
Myeloproliferative neoplasm	2A20	Approved	[2]
Pneumocystis pneumonia	CA40.20	Approved	[2]
Polymyalgia rheumatica	N.A.	Approved	[2]
Primary cutaneous T-cell lymphoma	N.A.	Approved	[2]
Psoriasis	EA90	Approved	[2]
Psoriatic arthritis	FA21	Approved	[2]
Rheumatic heart disease	N.A.	Approved	[2]
Rosacea	ED90.0	Approved	[2]
Sarcoidosis	4B20.5	Approved	[2]
Serum sickness	N.A.	Approved	[2]
Severe asthma	CA23	Approved	[2]
Skin disease	EA00-EM0Z	Approved	[2]
Solid tumour/cancer	2A00-2F9Z	Approved	[3]
Sympathetic ophthalmia	N.A.	Approved	[2]
Systemic lupus erythematosus	4A40.0	Approved	[2]
Ulcerative colitis	DD71	Approved	[2]
Multiple sclerosis	8A40	Phase 3	[4]
Acquired thrombocytopenia	N.A.	Investigative	[2]
Asthma	CA23	Investigative	[2]
Beta-thalassemia major	N.A.	Investigative	[2]
Classic Hodgkin lymphoma	N.A.	Investigative	[2]
Follicular lymphoma	2A80	Investigative	[2]
Iridocyclitis	N.A.	Investigative	[2]
Sjogren syndrome	4A43.20	Investigative	[2]
Synovitis	N.A.	Investigative	[2]
Uveitis	9A96.Z	Investigative	[2]

Prednisolone Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Glucocorticoid receptor (NR3C1)	TTYRL6O	GCR_HUMAN	Modulator	[11]

Prednisolone Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[12]

Prednisolone Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[13]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[14]

Prednisolone Interacts with 121 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Expression	[15]
CCN family member 1 (CCN1)	OTKJBEMD	CCN1_HUMAN	Increases Expression	[8]
Phospholipid phosphatase 3 (PLPP3)	OTSSF7BK	PLPP3_HUMAN	Decreases Expression	[8]
Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3)	OTPGHZB9	IFIT3_HUMAN	Decreases Expression	[8]
Calmegin (CLGN)	OTEWVFQV	CLGN_HUMAN	Decreases Expression	[8]
D-3-phosphoglycerate dehydrogenase (PHGDH)	OT1LMRTG	SERA_HUMAN	Decreases Expression	[8]
Receptor-interacting serine/threonine-protein kinase 2 (RIPK2)	OT0KMIYQ	RIPK2_HUMAN	Decreases Expression	[8]
Gasdermin-E (GSDME)	OT1ZWY32	GSDME_HUMAN	Decreases Expression	[8]
Toll-like receptor 2 (TLR2)	OTGO5P4R	TLR2_HUMAN	Decreases Expression	[8]
CCN family member 5 (CCN5)	OTADU8JJ	CCN5_HUMAN	Increases Expression	[8]
Antiviral innate immune response receptor RIG-I (RIGI)	OTFIIC43	RIGI_HUMAN	Decreases Expression	[8]
2'-5'-oligoadenylate synthase 1 (OAS1)	OT8ZLOCY	OAS1_HUMAN	Decreases Expression	[8]
Collagen alpha-1(I) chain (COL1A1)	OTI31178	CO1A1_HUMAN	Increases Expression	[8]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Decreases Expression	[8]
Ubiquitin-like protein ISG15 (ISG15)	OT53QQ7N	ISG15_HUMAN	Decreases Expression	[8]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Decreases Expression	[8]
Thrombospondin-1 (THBS1)	OT0ECWK3	TSP1_HUMAN	Increases Expression	[8]
Asparagine synthetase (ASNS)	OT8R922G	ASNS_HUMAN	Decreases Expression	[8]
Hepatocyte growth factor receptor (MET)	OT7K55MU	MET_HUMAN	Decreases Expression	[8]
Steryl-sulfatase (STS)	OTXTJQPC	STS_HUMAN	Increases Expression	[8]
Neuromedin-B (NMB)	OT4NLN6H	NMB_HUMAN	Decreases Expression	[8]
Stromelysin-2 (MMP10)	OTJDWW8Q	MMP10_HUMAN	Decreases Expression	[8]
Growth-regulated alpha protein (CXCL1)	OT3WCTZV	GROA_HUMAN	Decreases Expression	[8]
Interferon alpha-inducible protein 6 (IFI6)	OTWOOAM4	IFI6_HUMAN	Decreases Expression	[8]
Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1)	OTXOQDSG	IFIT1_HUMAN	Decreases Expression	[8]
Interleukin-1 receptor antagonist protein (IL1RN)	OT308CBE	IL1RA_HUMAN	Decreases Expression	[8]
C-X-C motif chemokine 2 (CXCL2)	OTEJCYMY	CXCL2_HUMAN	Decreases Expression	[8]
C-X-C motif chemokine 3 (CXCL3)	OTSL94KH	CXCL3_HUMAN	Decreases Expression	[8]
Interferon-induced GTP-binding protein Mx1 (MX1)	OT6X8G5T	MX1_HUMAN	Decreases Expression	[8]
Fibulin-1 (FBLN1)	OT5MHHOP	FBLN1_HUMAN	Increases Expression	[8]
Atypical chemokine receptor 3 (ACKR3)	OTA6GA4F	ACKR3_HUMAN	Decreases Expression	[8]
11-beta-hydroxysteroid dehydrogenase 1 (HSD11B1)	OTO7FJA9	DHI1_HUMAN	Decreases Expression	[8]
Adenosine receptor A2a (ADORA2A)	OTVRBZ0I	AA2AR_HUMAN	Decreases Expression	[8]
CCN family member 2 (CCN2)	OTC39NSU	CCN2_HUMAN	Increases Expression	[8]
Myristoylated alanine-rich C-kinase substrate (MARCKS)	OT7N056G	MARCS_HUMAN	Decreases Expression	[8]
Guanylate-binding protein 1 (GBP1)	OTUM7RPJ	GBP1_HUMAN	Decreases Expression	[8]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Decreases Expression	[8]
Macrophage metalloelastase (MMP12)	OT9Z7LHM	MMP12_HUMAN	Decreases Expression	[8]
Interferon alpha-inducible protein 27, mitochondrial (IFI27)	OTI2XGIT	IFI27_HUMAN	Decreases Expression	[8]
Regulator of G-protein signaling 4 (RGS4)	OTG94HHL	RGS4_HUMAN	Decreases Expression	[8]
Prolargin (PRELP)	OT9EEBUJ	PRELP_HUMAN	Increases Expression	[8]
Spermine synthase (SMS)	OT8JYKNH	SPSY_HUMAN	Decreases Expression	[8]
C-X-C chemokine receptor type 4 (CXCR4)	OTUFSBX2	CXCR4_HUMAN	Decreases Expression	[8]
C-C motif chemokine 20 (CCL20)	OTUCJY4N	CCL20_HUMAN	Decreases Expression	[8]
DNA-binding protein inhibitor ID-3 (ID3)	OTUULW5Z	ID3_HUMAN	Increases Expression	[8]
Tumor necrosis factor alpha-induced protein 2 (TNFAIP2)	OTRZH80H	TNAP2_HUMAN	Decreases Expression	[8]
Aldehyde oxidase (AOX1)	OT2FZP6H	AOXA_HUMAN	Increases Expression	[8]
Bone marrow stromal antigen 2 (BST2)	OTU4LCJV	BST2_HUMAN	Decreases Expression	[8]
EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1)	OTZVUOOB	FBLN3_HUMAN	Increases Expression	[8]
Neuronal membrane glycoprotein M6-b (GPM6B)	OT8Q1582	GPM6B_HUMAN	Increases Expression	[8]
Laminin subunit beta-3 (LAMB3)	OTFPU6W8	LAMB3_HUMAN	Decreases Expression	[8]
Nidogen-2 (NID2)	OTHC33FF	NID2_HUMAN	Increases Expression	[8]
Signal transducer and activator of transcription 4 (STAT4)	OTAK3VFR	STAT4_HUMAN	Decreases Expression	[8]
2'-5'-oligoadenylate synthase-like protein (OASL)	OTZ05YRP	OASL_HUMAN	Decreases Expression	[8]
Bcl-2-related protein A1 (BCL2A1)	OTWRYSNA	B2LA1_HUMAN	Decreases Expression	[8]
Lymphocyte antigen 6E (LY6E)	OTMG16BZ	LY6E_HUMAN	Decreases Expression	[8]
Interferon-induced protein 44-like (IFI44L)	OTXKORJP	IF44L_HUMAN	Decreases Expression	[8]
Olfactomedin-like protein 2B (OLFML2B)	OTDNJFR4	OLM2B_HUMAN	Increases Expression	[8]
E3 ubiquitin-protein ligase RNF19B (RNF19B)	OTYCWKBP	RN19B_HUMAN	Decreases Expression	[8]
Amphoterin-induced protein 2 (AMIGO2)	OTPAIT1O	AMGO2_HUMAN	Decreases Expression	[8]
Probable E3 ubiquitin-protein ligase HERC6 (HERC6)	OT7G9PQE	HERC6_HUMAN	Decreases Expression	[8]
Equilibrative nucleobase transporter 1 (SLC43A3)	OTR60ZLA	S43A3_HUMAN	Decreases Expression	[8]
Interferon-induced protein 44 (IFI44)	OTOKSZVA	IFI44_HUMAN	Decreases Expression	[8]
S-adenosylmethionine-dependent nucleotide dehydratase RSAD2 (RSAD2)	OTCA9WCM	RSAD2_HUMAN	Decreases Expression	[8]
Nuclear receptor subfamily 4 group A member 3 (NR4A3)	OTPBE9R1	NR4A3_HUMAN	Decreases Expression	[8]
Type II iodothyronine deiodinase (DIO2)	OTGPNSLH	IOD2_HUMAN	Increases Expression	[8]
Interferon regulatory factor 7 (IRF7)	OTC1A2PQ	IRF7_HUMAN	Decreases Expression	[8]
Interferon-stimulated gene 20 kDa protein (ISG20)	OTCWRJJW	ISG20_HUMAN	Decreases Expression	[8]
Interferon-induced helicase C domain-containing protein 1 (IFIH1)	OTZA2AHA	IFIH1_HUMAN	Decreases Expression	[8]
Anthrax toxin receptor 1 (ANTXR1)	OT5W1GPC	ANTR1_HUMAN	Increases Expression	[8]
Interleukin-23 subunit alpha (IL23A)	OTYO99HC	IL23A_HUMAN	Decreases Expression	[8]
NADH dehydrogenase 1 alpha subcomplex subunit 4-like 2 (NDUFA4L2)	OTK0PG7R	NUA4L_HUMAN	Decreases Expression	[8]
Large neutral amino acids transporter small subunit 2 (SLC7A8)	OT8XXVO8	LAT2_HUMAN	Increases Expression	[8]
E3 ISG15--protein ligase HERC5 (HERC5)	OTZ5PR39	HERC5_HUMAN	Decreases Expression	[8]
Paired immunoglobulin-like type 2 receptor alpha (PILRA)	OTBE0PLF	PILRA_HUMAN	Decreases Expression	[8]
Cystine/glutamate transporter (SLC7A11)	OTKJ6PXW	XCT_HUMAN	Decreases Expression	[8]
Cytochrome P450 2S1 (CYP2S1)	OTKHX4RF	CP2S1_HUMAN	Decreases Expression	[16]
Hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1)	OTCO26FV	HMCS1_HUMAN	Increases Expression	[9]
Inactive phospholipase C-like protein 1 (PLCL1)	OTJL2C79	PLCL1_HUMAN	Increases Expression	[9]
Cyclin-G2 (CCNG2)	OTII38K2	CCNG2_HUMAN	Increases Expression	[9]
Programmed cell death protein 4 (PDCD4)	OTZ6NXUX	PDCD4_HUMAN	Increases Expression	[9]
Kelch-like protein 24 (KLHL24)	OTWZSX5C	KLH24_HUMAN	Increases Expression	[9]
Protein FAM200C (FAM200C)	OTZOXUEK	F200C_HUMAN	Increases Expression	[9]
Arrestin domain-containing protein 3 (ARRDC3)	OTAKW7R9	ARRD3_HUMAN	Increases Expression	[9]
Sulfiredoxin-1 (SRXN1)	OTYDBO4L	SRXN1_HUMAN	Increases Expression	[9]
Cysteine-rich motor neuron 1 protein (CRIM1)	OTTZNV6Y	CRIM1_HUMAN	Increases Expression	[9]
SLAM family member 5 (CD84)	OTAY5B0F	SLAF5_HUMAN	Increases Expression	[9]
PDZ and LIM domain protein 1 (PDLIM1)	OT4EGCPG	PDLI1_HUMAN	Increases Expression	[17]
Basic helix-loop-helix ARNT-like protein 1 (BMAL1)	OTMI12L2	BMAL1_HUMAN	Increases Expression	[18]
Period circadian protein homolog 2 (PER2)	OTU2B1DJ	PER2_HUMAN	Decreases Expression	[18]
Period circadian protein homolog 1 (PER1)	OTVQF3WX	PER1_HUMAN	Increases Expression	[18]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Decreases Expression	[19]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Increases Expression	[20]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Decreases Expression	[17]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Increases Expression	[21]
Serotransferrin (TF)	OT41PEMS	TRFE_HUMAN	Increases Expression	[21]
Glucocorticoid receptor (NR3C1)	OTCI2YDI	GCR_HUMAN	Increases Activity	[22]
Insulin-like growth factor I (IGF1)	OTIIZR61	IGF1_HUMAN	Decreases Response To Substance	[23]
Interleukin-4 (IL4)	OTOXBWAU	IL4_HUMAN	Decreases Expression	[24]
Interleukin-5 (IL5)	OTAFPSCO	IL5_HUMAN	Decreases Expression	[24]
Mineralocorticoid receptor (NR3C2)	OT0F2V2Z	MCR_HUMAN	Increases Activity	[22]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Decreases Expression	[17]
C-C motif chemokine 3 (CCL3)	OTW2H3ND	CCL3_HUMAN	Increases Expression	[10]
C-C motif chemokine 4 (CCL4)	OT6B8P25	CCL4_HUMAN	Increases Expression	[10]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Decreases Expression	[10]
Ganglioside GM2 activator (GM2A)	OTIRWZC0	SAP3_HUMAN	Increases Expression	[17]
Nuclear receptor subfamily 1 group D member 1 (NR1D1)	OTJ38PTB	NR1D1_HUMAN	Decreases Expression	[18]
C-X-C chemokine receptor type 2 (CXCR2)	OTISGW7L	CXCR2_HUMAN	Decreases Expression	[25]
Long-chain-fatty-acid--CoA ligase 1 (ACSL1)	OTB06ESI	ACSL1_HUMAN	Increases Expression	[17]
Growth/differentiation factor 5 (GDF5)	OTOV8S81	GDF5_HUMAN	Decreases Expression	[26]
Tissue factor pathway inhibitor 2 (TFPI2)	OTZCRWOR	TFPI2_HUMAN	Decreases Expression	[17]
Transcription factor SOX-9 (SOX9)	OTVDJFGN	SOX9_HUMAN	Decreases Expression	[17]
D site-binding protein (DBP)	OTE0W7LN	DBP_HUMAN	Decreases Expression	[18]
Cryptochrome-1 (CRY1)	OTTGAJT0	CRY1_HUMAN	Decreases Expression	[18]
Mucin-16 (MUC16)	OTHPPE67	MUC16_HUMAN	Decreases Expression	[27]
Lymphocyte antigen 96 (LY96)	OTN4HXA2	LY96_HUMAN	Decreases Expression	[17]
DNA topoisomerase 1 (TOP1)	OT51O0CF	TOP1_HUMAN	Increases ADR	[28]
Histone-lysine N-methyltransferase 2A (KMT2A)	OT9GLJI6	KMT2A_HUMAN	Decreases Response To Substance	[29]
11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2)	OTHF4H9U	DHI2_HUMAN	Increases Metabolism	[30]
Mothers against decapentaplegic homolog 1 (SMAD1)	OTQSHR25	SMAD1_HUMAN	Increases ADR	[28]
Catenin beta-1 (CTNNB1)	OTZ932A3	CTNB1_HUMAN	Increases ADR	[28]

Indication(s) of Hydroxychloroquine

Disease Entry	ICD 11	Status	REF
Chronic renal failure	GB61.Z	Approved	[5]
Malaria	1F40-1F45	Approved	[6]
Plasmodium falciparum malaria	1F40	Approved	[5]
Plasmodium malariae malaria	N.A.	Approved	[5]
Plasmodium ovale malaria	N.A.	Approved	[5]
Systemic lupus erythematosus	4A40.0	Approved	[5]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[7]
Colon cancer	2B90.Z	Investigative	[5]

Hydroxychloroquine Interacts with 4 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
HUMAN pH-dependent viral fusion/replication (pH-DVF/R)	TTD16BI	N.A.	Inhibitor	[31]
HUMAN glycosylation of host receptor (GHR)	TTZGK1R	N.A.	Inhibitor	[31]
Toll-like receptor 7 (TLR7)	TTRJ1K4	TLR7_HUMAN	Antagonist	[32]
HUMAN toll-like receptor 7/9 signalling pathway (TLR7/9 pathway)	TT3A1EZ	N.A.	Inhibitor	[33]

Hydroxychloroquine Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[34]

Hydroxychloroquine Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[35]

Hydroxychloroquine Interacts with 30 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Decreases Activity	[36]
Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3)	OTPGHZB9	IFIT3_HUMAN	Increases Expression	[37]
CASP8 and FADD-like apoptosis regulator (CFLAR)	OTX14BAS	CFLAR_HUMAN	Decreases Expression	[38]
Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1)	OTY9R6FZ	ERN1_HUMAN	Increases Expression	[37]
Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1)	OT4TMERS	NFAC1_HUMAN	Affects Expression	[39]
Claudin-1 (CLDN1)	OT27KV99	CLD1_HUMAN	Increases Expression	[40]
Interferon beta (IFNB1)	OTYQGUB5	IFNB_HUMAN	Increases Expression	[37]
C-X-C motif chemokine 10 (CXCL10)	OTTLQ6S0	CXL10_HUMAN	Increases Expression	[37]
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR)	OTRT3F3U	HMDH_HUMAN	Affects Expression	[41]
Alkaline phosphatase, tissue-nonspecific isozyme (ALPL)	OTG7J4BP	PPBT_HUMAN	Affects Expression	[41]
Transcription factor Jun (JUN)	OTCYBO6X	JUN_HUMAN	Increases Phosphorylation	[37]
Cathepsin B (CTSB)	OTP9G5QB	CATB_HUMAN	Affects Localization	[42]
72 kDa type IV collagenase (MMP2)	OT5NIWA2	MMP2_HUMAN	Decreases Expression	[43]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[44]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Expression	[44]
NF-kappa-B inhibitor alpha (NFKBIA)	OTFT924M	IKBA_HUMAN	Increases Degradation	[37]
CD40 ligand (CD40LG)	OT75Z6A6	CD40L_HUMAN	Decreases Expression	[39]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[38]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Increases Expression	[37]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Activity	[42]
TNF receptor-associated factor 3 (TRAF3)	OT5TQBGV	TRAF3_HUMAN	Increases Expression	[37]
Nuclear factor of activated T-cells, cytoplasmic 2 (NFATC2)	OTK5T6HZ	NFAC2_HUMAN	Affects Localization	[39]
Sequestosome-1 (SQSTM1)	OTGY5D5J	SQSTM_HUMAN	Increases Expression	[45]
Interferon regulatory factor 3 (IRF3)	OT81U8ME	IRF3_HUMAN	Increases Phosphorylation	[37]
Occludin (OCLN)	OTSUTVWL	OCLN_HUMAN	Increases Expression	[40]
Mitochondrial antiviral-signaling protein (MAVS)	OTTQ0J64	MAVS_HUMAN	Increases Expression	[37]
S-adenosylmethionine-dependent nucleotide dehydratase RSAD2 (RSAD2)	OTCA9WCM	RSAD2_HUMAN	Increases Expression	[37]
Interferon-induced helicase C domain-containing protein 1 (IFIH1)	OTZA2AHA	IFIH1_HUMAN	Increases Expression	[37]
Toll-like receptor 9 (TLR9)	OTFZ45HX	TLR9_HUMAN	Decreases Expression	[46]
7-dehydrocholesterol reductase (DHCR7)	OTLILBUI	DHCR7_HUMAN	Affects Expression	[41]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Inflammatory Cardiomyopathy	DCP777J	N. A.	Phase 2	[47]
Lupus Nephritis	DC2LI4D	N. A.	Phase 1	[1]

References

• [1] ClinicalTrials.gov (NCT03791827) Multicenter Registry of Pediatric Lupus Nephritis in China
• [2] Prednisolone FDA Label
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] 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: 2866).
• [5] Hydroxychloroquine FDA Label
• [6] 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: 7198).
• [7] ClinicalTrials.gov (NCT04341727) Hydroxychloroquine,Hydroxychloroquine,Azithromycin in the Treatment of SARS CoV-2 Infection (WU352). U.S. National Institutes of Health.
• [8] Antirheumatic drug response signatures in human chondrocytes: potential molecular targets to stimulate cartilage regeneration. Arthritis Res Ther. 2009;11(1):R15.
• [9] Transcriptome-based functional classifiers for direct immunotoxicity. Arch Toxicol. 2014 Mar;88(3):673-89.
• [10] Cell-based and cytokine-directed chemical screen to identify potential anti-multiple myeloma agents. Leuk Res. 2010 Jul;34(7):917-24. doi: 10.1016/j.leukres.2009.12.002. Epub 2010 Feb 8.
• [11] Aldosterone (mineralocorticoid) equivalent to prednisolone (glucocorticoid) in reversing hearing loss in MRL/MpJ-Fas1pr autoimmune mice. Laryngoscope. 2000 Nov;110(11):1902-6.
• [12] The role of the efflux transporter P-glycoprotein in brain penetration of prednisolone. J Endocrinol. 2002 Oct;175(1):251-60.
• [13] Inter-individual difference determinant of prednisolone pharmacokinetics for Japanese renal transplant recipients in the maintenance stage. Xenobiotica. 2009 Dec;39(12):939-45.
• [14] Pharmacokinetic and pharmacoimmunodynamic interactions between prednisolone and sirolimus in adrenalectomized rats. J Pharmacokinet Biopharm. 1999 Feb;27(1):1-21.
• [15] Induction of CYP3As in HepG2 cells by several drugs. Association between induction of CYP3A4 and expression of glucocorticoid receptor. Biol Pharm Bull. 2003 Apr;26(4):510-7.
• [16] CYP2S1 is negatively regulated by corticosteroids in human cell lines. Toxicol Lett. 2012 Feb 25;209(1):30-4.
• [17] Gene expression profiling of rheumatoid arthritis synovial cells treated with antirheumatic drugs. J Biomol Screen. 2007 Apr;12(3):328-40. doi: 10.1177/1087057107299261. Epub 2007 Mar 22.
• [18] Chronic treatment with prednisolone represses the circadian oscillation of clock gene expression in mouse peripheral tissues. Mol Endocrinol. 2006 Mar;20(3):573-83. doi: 10.1210/me.2005-0165. Epub 2005 Nov 3.
• [19] Steroid therapy and urinary transforming growth factor-beta1 in IgA nephropathy. Am J Kidney Dis. 2001 Dec;38(6):1191-8. doi: 10.1053/ajkd.2001.29209.
• [20] Contrasting effects of steroids and angiotensin-converting-enzyme inhibitors in a mouse model of dystrophin-deficient cardiomyopathy. Eur J Heart Fail. 2009 May;11(5):463-71. doi: 10.1093/eurjhf/hfp028. Epub 2009 Feb 20.
• [21] Prednisolone can increase glomerular permeability to proteins in nephrotic syndrome. Kidney Int. 1988 Jun;33(6):1169-74. doi: 10.1038/ki.1988.126.
• [22] Transactivation via the human glucocorticoid and mineralocorticoid receptor by therapeutically used steroids in CV-1 cells: a comparison of their glucocorticoid and mineralocorticoid properties. Eur J Endocrinol. 2004 Sep;151(3):397-406. doi: 10.1530/eje.0.1510397.
• [23] Anti-TNF antibody treatment improves glucocorticoid induced insulin-like growth factor 1 (IGF1) resistance without influencing myoglobin and IGF1 binding proteins 1 and 3. Ann Rheum Dis. 2006 Mar;65(3):301-5. doi: 10.1136/ard.2005.040816. Epub 2005 Aug 3.
• [24] JTP-27536 [(+)-1,3-dihydroxy-2-hydroxymethylpropyl-2-ammonium 2-[(R)-3-cyclo-hexyl-1-phenylpropyl]-1,3-dioxo-2,3-dihydro-1H-isoindole-5-carboxylate monohydrate], a novel inhibitor of immunoglobulins and interleukin-5 with anti-inflammatory properties in mouse allergic dermatitis model. J Pharmacol Exp Ther. 2005 Jul;314(1):293-301. doi: 10.1124/jpet.104.080846. Epub 2005 Apr 8.
• [25] CXCR2 Expression on neutrophils is upregulated during the relapsing phase of ocular Behcet disease. Curr Eye Res. 2005 Mar;30(3):195-203. doi: 10.1080/02713680490904331.
• [26] Modulatory effects of inflammation and therapy on GDF-5 expression in rheumatoid arthritis synovium. Scand J Rheumatol. 2008 Nov-Dec;37(6):401-9. doi: 10.1080/03009740802120010.
• [27] Dermatomyositis associated with membranous nephropathy in a 43-year-old female. Am J Nephrol. 2002 Jul-Aug;22(4):385-8. doi: 10.1159/000065233.
• [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] In vitro drug-resistance profile in infant acute lymphoblastic leukemia in relation to age, MLL rearrangements and immunophenotype. Leukemia. 2004 Mar;18(3):521-9. doi: 10.1038/sj.leu.2403253.
• [30] Metabolism of synthetic steroids by the human placenta. Placenta. 2007 Jan;28(1):39-46.
• [31] Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020 Mar;30(3):269-271.
• [32] TLR7/9 antagonists as therapeutics for immune-mediated inflammatory disorders. Inflamm Allergy Drug Targets. 2007 Dec;6(4):223-35.
• [33] Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. Nat Rev Rheumatol. 2020 Mar;16(3):155-166.
• [34] MDR-ABC transporters: biomarkers in rheumatoid arthritis. Clin Exp Rheumatol. 2013 Sep-Oct;31(5):779-87.
• [35] Hydroxychloroquine: a physiologically-based pharmacokinetic model in the context of cancer-related autophagy modulation. J Pharmacol Exp Ther. 2018 Jun;365(3):447-459.
• [36] Somer M, Kallio J, Pesonen U, Pyykko K, Huupponen R, Scheinin M "Influence of hydroxychloroquine on the bioavailability of oral metoprolol." Br J Clin Pharmacol 49 (2000): 549-54. [PMID: 10848718]
• [37] Hydroxychloroquine-inhibited dengue virus is associated with host defense machinery. J Interferon Cytokine Res. 2015 Mar;35(3):143-56. doi: 10.1089/jir.2014.0038. Epub 2014 Oct 16.
• [38] Hydroxychloroquine potentiates Fas-mediated apoptosis of rheumatoid synoviocytes. Clin Exp Immunol. 2006 Jun;144(3):503-11. doi: 10.1111/j.1365-2249.2006.03070.x.
• [39] Hydroxychloroquine inhibits CD154 expression in CD4(+) T lymphocytes of systemic lupus erythematosus through NFAT, but not STAT5, signaling. Arthritis Res Ther. 2017 Aug 9;19(1):183. doi: 10.1186/s13075-017-1393-y.
• [40] Chloroquine and Hydroxychloroquine Increase Retinal Pigment Epithelial Layer Permeability. J Biochem Mol Toxicol. 2015 Jul;29(7):299-304. doi: 10.1002/jbt.21696. Epub 2015 Mar 9.
• [41] Hydroxychloroquine decreases human MSC-derived osteoblast differentiation and mineralization in vitro. J Cell Mol Med. 2018 Feb;22(2):873-882. doi: 10.1111/jcmm.13373. Epub 2017 Oct 3.
• [42] Mitochondrial membrane permeabilization is a critical step of lysosome-initiated apoptosis induced by hydroxychloroquine. Oncogene. 2003 Jun 19;22(25):3927-36. doi: 10.1038/sj.onc.1206622.
• [43] Attenuation of chloroquine and hydroxychloroquine on the invasive potential of bladder cancer through targeting matrix metalloproteinase 2 expression. Environ Toxicol. 2021 Nov;36(11):2138-2145. doi: 10.1002/tox.23328. Epub 2021 Jul 19.
• [44] Reactive oxygen species mediate chloroquine-induced expression of chemokines by human astroglial cells. Glia. 2004 Jul;47(1):9-20. doi: 10.1002/glia.20017.
• [45] d-galactose induces premature senescence of lens epithelial cells by disturbing autophagy flux and mitochondrial functions. Toxicol Lett. 2018 Jun 1;289:99-106. doi: 10.1016/j.toxlet.2018.02.001. Epub 2018 Feb 6.
• [46] Antagonist-mediated down-regulation of Toll-like receptors increases the prevalence of human papillomavirus infection in systemic lupus erythematosus. Arthritis Res Ther. 2012 Apr 18;14(2):R80. doi: 10.1186/ar3803.
• [47] ClinicalTrials.gov (NCT05961202) The Effects of Hydroxychloroquine in Patients With Inflammatory Cardiomyopathy