Details of the Drug Combination

General Information of Drug Combination (ID: DC55Y85)

• Drug Combination Name: Hydrocortisone + Fludrocortisone
• Indication: Renin Angiotensin; Status: Phase 1 [1]
• Component Drugs:
  Hydrocortisone (DMGEMB7): Small molecular drug
  Fludrocortisone (DMUDIR8): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Hydrocortisone

Disease Entry	ICD 11	Status	REF
Acne vulgaris	ED80	Approved	[2]
Acute adrenal insufficiency	N.A.	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]
Corneal abrasion	NA06.4	Approved	[2]
Corneal ulcer	9A76	Approved	[2]
Crohn disease	DD70	Approved	[2]
Dermatitis herpetiformis	EB44	Approved	[2]
Diamond-Blackfan anemia	N.A.	Approved	[2]
Disorder of orbital region	N.A.	Approved	[2]
Erythema multiforme	N.A.	Approved	[2]
Exanthem	N.A.	Approved	[2]
Gingival disorder	N.A.	Approved	[2]
Granuloma annulare	N.A.	Approved	[2]
Inflammation	1A00-CA43.1	Approved	[3]
Inflammatory bowel disease	DD72	Approved	[2]
Keratitis	N.A.	Approved	[2]
Malignant otitis externa caused by Pseudomonas aeruginosa	N.A.	Approved	[2]
Multiple sclerosis	8A40	Approved	[2]
Mycosis fungoides	2B01	Approved	[2]
Primary cutaneous T-cell lymphoma	N.A.	Approved	[2]
Proctitis	DB33.Z	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]
Systemic lupus erythematosus	4A40.0	Approved	[2]
Tinea corporis	1F28.Y	Approved	[2]
Tinea cruris	1F28.3	Approved	[2]
Ulcerative colitis	DD71	Approved	[2]
Viral pneumonia	N.A.	Approved	[2]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[4]
Congenital adrenal hyperplasia	5A71.01	Phase 2	[5]
Acquired thrombocytopenia	N.A.	Investigative	[2]
Asthma	CA23	Investigative	[2]
Beta-thalassemia major	N.A.	Investigative	[2]
Classic Hodgkin lymphoma	N.A.	Investigative	[2]
Iridocyclitis	N.A.	Investigative	[2]
Phobic disorder	N.A.	Investigative	[2]
Rheumatoid arthritis	FA20	Investigative	[2]
Synovitis	N.A.	Investigative	[2]
Tinea pedis	1F28.2	Investigative	[2]
Trichinellosis	N.A.	Investigative	[2]
Uveitis	9A96.Z	Investigative	[2]

Hydrocortisone Interacts with 1 DTT Molecule(s)

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

Hydrocortisone 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]

Hydrocortisone Interacts with 5 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]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[15]
Steroid 11-beta-hydroxylase (CYP11B1)	DEPE0RD	C11B1_HUMAN	Metabolism	[16]
Aldosterone synthase (CYP11B2)	DE6TYUK	C11B2_HUMAN	Metabolism	[16]

Hydrocortisone Interacts with 108 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 11B1, mitochondrial (CYP11B1)	OTKKL894	C11B1_HUMAN	Increases Chemical Synthesis	[17]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Expression	[18]
Cytochrome P450 3A5 (CYP3A5)	OTSXFBXB	CP3A5_HUMAN	Increases Expression	[19]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Secretion	[20]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Decreases Secretion	[21]
Glutathione S-transferase A1 (GSTA1)	OTA7K5XA	GSTA1_HUMAN	Increases Expression	[22]
Protein-glutamine gamma-glutamyltransferase K (TGM1)	OTB8URRI	TGM1_HUMAN	Increases Expression	[23]
GDH/6PGL endoplasmic bifunctional protein (H6PD)	OTO7TNDD	G6PE_HUMAN	Increases Expression	[24]
11-beta-hydroxysteroid dehydrogenase 1 (HSD11B1)	OTO7FJA9	DHI1_HUMAN	Increases Expression	[24]
Disintegrin and metalloproteinase domain-containing protein 12 (ADAM12)	OTZKOTDB	ADA12_HUMAN	Decreases Expression	[25]
Mitogen-activated protein kinase kinase kinase 7 (MAP3K7)	OTUXEASC	M3K7_HUMAN	Decreases Expression	[25]
Integrin alpha-10 (ITGA10)	OTM0V5AO	ITA10_HUMAN	Increases Expression	[25]
Glucocorticoid receptor (NR3C1)	OTCI2YDI	GCR_HUMAN	Decreases Expression	[25]
Integrin alpha-5 (ITGA5)	OT3RCI67	ITA5_HUMAN	Increases Expression	[25]
Amine oxidase A (MAOA)	OT8NIWMQ	AOFA_HUMAN	Increases Expression	[25]
Insulin-like growth factor-binding protein 5 (IGFBP5)	OTRE5V0C	IBP5_HUMAN	Decreases Expression	[25]
Adhesion G protein-coupled receptor E5 (ADGRE5)	OTTSB84Q	AGRE5_HUMAN	Decreases Expression	[25]
Metallothionein-1X (MT1X)	OT9AKFVS	MT1X_HUMAN	Increases Expression	[25]
Collagen alpha-1(VII) chain (COL7A1)	OT3MIRZJ	CO7A1_HUMAN	Decreases Expression	[25]
Forkhead box protein O1 (FOXO1)	OTPJRB6D	FOXO1_HUMAN	Increases Expression	[25]
Peptidyl-prolyl cis-trans isomerase FKBP5 (FKBP5)	OT404F9K	FKBP5_HUMAN	Increases Expression	[25]
Nuclear receptor subfamily 6 group A member 1 (NR6A1)	OTFZOOQ9	NR6A1_HUMAN	Decreases Expression	[25]
Protein prune homolog 2 (PRUNE2)	OTGW2974	PRUN2_HUMAN	Decreases Expression	[25]
Adhesion G-protein coupled receptor G1 (ADGRG1)	OTQBB8NT	AGRG1_HUMAN	Decreases Expression	[25]
Cytochrome P450 2S1 (CYP2S1)	OTKHX4RF	CP2S1_HUMAN	Decreases Expression	[26]
3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1)	OTNAZVKB	3BHS1_HUMAN	Affects Binding	[27]
Insulin-like growth factor I (IGF1)	OTIIZR61	IGF1_HUMAN	Decreases Expression	[28]
Insulin-like growth factor 1 receptor (IGF1R)	OTXJIF13	IGF1R_HUMAN	Affects Expression	[28]
CCAAT/enhancer-binding protein beta (CEBPB)	OTM9MQIA	CEBPB_HUMAN	Affects Expression	[28]
Steroidogenic acute regulatory protein, mitochondrial (STAR)	OTFEZ5AI	STAR_HUMAN	Decreases Expression	[28]
CCAAT/enhancer-binding protein alpha (CEBPA)	OTOM9OE4	CEBPA_HUMAN	Increases Expression	[28]
11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2)	OTHF4H9U	DHI2_HUMAN	Decreases Expression	[28]
Low-density lipoprotein receptor (LDLR)	OTH559LU	LDLR_HUMAN	Decreases Expression	[29]
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR)	OTRT3F3U	HMDH_HUMAN	Decreases Expression	[29]
Apolipoprotein B-100 (APOB)	OTH0UOCZ	APOB_HUMAN	Decreases Expression	[29]
RAC-beta serine/threonine-protein kinase (AKT2)	OTBB632K	AKT2_HUMAN	Decreases Expression	[29]
Scavenger receptor class B member 1 (SCARB1)	OTAE1UA1	SCRB1_HUMAN	Decreases Expression	[29]
Toll-like receptor 4 (TLR4)	OTP7ML3S	TLR4_HUMAN	Decreases Expression	[30]
Basic helix-loop-helix ARNT-like protein 1 (BMAL1)	OTMI12L2	BMAL1_HUMAN	Decreases Expression	[10]
Dihydroxyacetone phosphate acyltransferase (GNPAT)	OTF6LWPO	GNPAT_HUMAN	Increases Expression	[8]
ATP-binding cassette sub-family C member 3 (ABCC3)	OTC3IJV4	MRP3_HUMAN	Increases Expression	[31]
Period circadian protein homolog 1 (PER1)	OTVQF3WX	PER1_HUMAN	Increases Expression	[10]
Trehalase (TREH)	OTJE0NOY	TREA_HUMAN	Decreases Activity	[32]
Toll-like receptor 2 (TLR2)	OTGO5P4R	TLR2_HUMAN	Increases Expression	[30]
Rap guanine nucleotide exchange factor 3 (RAPGEF3)	OTMOW4Z4	RPGF3_HUMAN	Increases Expression	[8]
Renin (REN)	OT52GZR2	RENI_HUMAN	Decreases Expression	[33]
Antithrombin-III (SERPINC1)	OTDFATG0	ANT3_HUMAN	Increases Expression	[34]
Natriuretic peptides A (NPPA)	OTMQNTNX	ANF_HUMAN	Increases Expression	[35]
Somatotropin (GH1)	OT92RTRD	SOMA_HUMAN	Increases Expression	[36]
Pro-neuropeptide Y (NPY)	OT4ICV3P	NPY_HUMAN	Affects Expression	[37]
Insulin (INS)	OTZ85PDU	INS_HUMAN	Increases Expression	[35]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Decreases Expression	[10]
Interleukin-1 alpha (IL1A)	OTPSGILV	IL1A_HUMAN	Decreases Expression	[10]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Decreases Expression	[38]
Erythropoietin (EPO)	OTZ90CN4	EPO_HUMAN	Increases Expression	[39]
Annexin A1 (ANXA1)	OT5OFDJC	ANXA1_HUMAN	Increases Expression	[8]
Cholesterol side-chain cleavage enzyme, mitochondrial (CYP11A1)	OT2NV3AN	CP11A_HUMAN	Decreases Expression	[40]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Decreases Expression	[34]
Kallikrein-1 (KLK1)	OTFGP3UR	KLK1_HUMAN	Increases Export	[35]
Prostate-specific antigen (KLK3)	OTFGSBFJ	KLK3_HUMAN	Increases Expression	[41]
Involucrin (IVL)	OT4VPNGY	INVO_HUMAN	Decreases Expression	[42]
Pulmonary surfactant-associated protein B (SFTPB)	OTOHS07E	PSPB_HUMAN	Increases Expression	[43]
Mineralocorticoid receptor (NR3C2)	OT0F2V2Z	MCR_HUMAN	Increases Activity	[44]
Monocyte differentiation antigen CD14 (CD14)	OT83GJ47	CD14_HUMAN	Decreases Expression	[30]
C-C motif chemokine 3 (CCL3)	OTW2H3ND	CCL3_HUMAN	Increases Expression	[45]
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Affects Activity	[46]
Pulmonary surfactant-associated protein C (SFTPC)	OTIZJD09	PSPC_HUMAN	Increases Expression	[43]
Proliferating cell nuclear antigen (PCNA)	OTHZ1RIA	PCNA_HUMAN	Decreases Expression	[9]
C-C motif chemokine 4 (CCL4)	OT6B8P25	CCL4_HUMAN	Increases Expression	[45]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Decreases Expression	[45]
Hepatocyte growth factor (HGF)	OTGHUA23	HGF_HUMAN	Decreases Expression	[47]
Filaggrin (FLG)	OTE9QDV6	FILA_HUMAN	Decreases Expression	[42]
Loricrin (LORICRIN)	OTFRPVEO	LORI_HUMAN	Decreases Expression	[42]
NF-kappa-B inhibitor alpha (NFKBIA)	OTFT924M	IKBA_HUMAN	Increases Expression	[8]
Dual specificity protein phosphatase 1 (DUSP1)	OTN6BR75	DUS1_HUMAN	Increases Expression	[10]
Cadherin-5 (CDH5)	OTVX0E1Q	CADH5_HUMAN	Increases Localization	[8]
T-lymphocyte activation antigen CD80 (CD80)	OTJBLUQE	CD80_HUMAN	Decreases Expression	[48]
Catenin beta-1 (CTNNB1)	OTZ932A3	CTNB1_HUMAN	Increases Localization	[8]
Nuclear receptor ROR-alpha (RORA)	OTGQT12P	RORA_HUMAN	Increases Expression	[10]
Sterol regulatory element-binding protein 1 (SREBF1)	OTWBRPAI	SRBP1_HUMAN	Increases Expression	[49]
Amiloride-sensitive sodium channel subunit alpha (SCNN1A)	OTE2KVZV	SCNNA_HUMAN	Increases Expression	[50]
T-lymphocyte activation antigen CD86 (CD86)	OTJCSBPC	CD86_HUMAN	Decreases Expression	[48]
Fatty acid synthase (FASN)	OTFII9KG	FAS_HUMAN	Increases Expression	[49]
Carnitine O-palmitoyltransferase 1, liver isoform (CPT1A)	OTI862QH	CPT1A_HUMAN	Decreases Expression	[49]
Amiloride-sensitive sodium channel subunit beta (SCNN1B)	OT61QQTL	SCNNB_HUMAN	Increases Expression	[50]
Amiloride-sensitive sodium channel subunit gamma (SCNN1G)	OTSJYQVQ	SCNNG_HUMAN	Increases Expression	[50]
ATP-citrate synthase (ACLY)	OTRL9ZRP	ACLY_HUMAN	Increases Expression	[49]
Ras-related protein Rap-1A (RAP1A)	OT5RH6TI	RAP1A_HUMAN	Increases Expression	[8]
Tight junction protein ZO-1 (TJP1)	OTBDCUPK	ZO1_HUMAN	Increases Localization	[8]
Acetyl-CoA carboxylase 1 (ACACA)	OT5CQPZY	ACACA_HUMAN	Increases Expression	[49]
Histone deacetylase 1 (HDAC1)	OTQDNOXZ	HDAC1_HUMAN	Increases Expression	[40]
Splicing factor 1 (SF1)	OTLEDM2S	SF01_HUMAN	Decreases Expression	[40]
Cryptochrome-1 (CRY1)	OTTGAJT0	CRY1_HUMAN	Increases Expression	[10]
Atypical chemokine receptor 1 (ACKR1)	OT9M11LX	ACKR1_HUMAN	Increases Expression	[8]
Occludin (OCLN)	OTSUTVWL	OCLN_HUMAN	Increases Expression	[8]
Patatin-like phospholipase domain-containing protein 2 (PNPLA2)	OTR3ERMR	PLPL2_HUMAN	Decreases Expression	[49]
NAD-dependent protein deacetylase sirtuin-1 (SIRT1)	OTAYZMOY	SIR1_HUMAN	Decreases Expression	[49]
TSC22 domain family protein 3 (TSC22D3)	OT03UM03	T22D3_HUMAN	Increases Expression	[8]
Corticoliberin (CRH)	OT2MOC4T	CRF_HUMAN	Increases Abundance	[51]
Oxytocin-neurophysin 1 (OXT)	OT48M72Z	NEU1_HUMAN	Affects Abundance	[52]
Aldo-keto reductase family 1 member D1 (AKR1D1)	OTBDJ6RL	AK1D1_HUMAN	Increases Reduction	[53]
Angiotensinogen (AGT)	OTBZLYR3	ANGT_HUMAN	Increases Secretion	[54]
Insulin-like growth factor II (IGF2)	OTJ4O6MW	IGF2_HUMAN	Increases Secretion	[55]
Histone-binding protein RBBP7 (RBBP7)	OTLB56HX	RBBP7_HUMAN	Affects Response To Substance	[56]
Glycodelin (PAEP)	OTQA0NV4	PAEP_HUMAN	Increases Metabolism	[57]
Pro-opiomelanocortin (POMC)	OTV41F7T	COLI_HUMAN	Increases Abundance	[58]
T-box transcription factor TBX19 (TBX19)	OTXEMR2U	TBX19_HUMAN	Decreases Abundance	[59]
Interferon beta (IFNB1)	OTYQGUB5	IFNB_HUMAN	Decreases Secretion	[55]

Indication(s) of Fludrocortisone

Disease Entry	ICD 11	Status	REF
Addison disease	5A74.0	Approved	[6]
Cerebral salt-wasting syndrome	5C72	Approved	[7]
Congenital adrenal hyperplasia	5A71.01	Approved	[6]

Fludrocortisone Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Androgen receptor (AR)	TTS64P2	ANDR_HUMAN	Inhibitor	[60]
Mineralocorticoid receptor (MR)	TT26PHO	MCR_HUMAN	Agonist	[61]

Fludrocortisone Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[62]

Fludrocortisone Interacts with 15 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Proepiregulin (EREG)	OTRM4NQY	EREG_HUMAN	Decreases Expression	[63]
Interleukin-1 alpha (IL1A)	OTPSGILV	IL1A_HUMAN	Decreases Expression	[63]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Decreases Expression	[63]
Antileukoproteinase (SLPI)	OTUNFUU8	SLPI_HUMAN	Increases Expression	[63]
Prostate-specific antigen (KLK3)	OTFGSBFJ	KLK3_HUMAN	Increases Expression	[41]
Hepatocyte growth factor receptor (MET)	OT7K55MU	MET_HUMAN	Increases Expression	[63]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Decreases Expression	[63]
C-C motif chemokine 3 (CCL3)	OTW2H3ND	CCL3_HUMAN	Increases Expression	[45]
C-C motif chemokine 4 (CCL4)	OT6B8P25	CCL4_HUMAN	Increases Expression	[45]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Decreases Expression	[45]
Bone morphogenetic protein 6 (BMP6)	OT9WN536	BMP6_HUMAN	Decreases Expression	[63]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Decreases Expression	[63]
Tumor necrosis factor-inducible gene 6 protein (TNFAIP6)	OT1SLUZH	TSG6_HUMAN	Decreases Expression	[63]
PTB-containing, cubilin and LRP1-interacting protein (PID1)	OT5YJ7FI	PCLI1_HUMAN	Increases Expression	[63]
Cystine/glutamate transporter (SLC7A11)	OTKJ6PXW	XCT_HUMAN	Decreases Expression	[63]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Septic Shock	DCJBBY2	N. A.	Phase 1	[64]

References

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