Details of the Drug Combination

General Information of Drug Combination (ID: DC6ZN1P)

• Drug Combination Name: Sulfasalazine + Loperamide
• Indication: Intestinal Obstruction; Status: Phase 1 [1]
• Component Drugs:
  Sulfasalazine (DMICA9H): Small molecular drug
  Loperamide (DMOJZQ9): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Sulfasalazine

Disease Entry	ICD 11	Status	REF
Irritable bowel syndrome	DD91.0	Approved	[2]
Rheumatoid arthritis	FA20	Approved	[3]
Ulcerative colitis	DD71	Approved	[4]

Sulfasalazine Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
ATP-binding cassette transporter G2 (ABCG2)	TTIMJ02	ABCG2_HUMAN	Inhibitor	[9]
Nuclear factor NF-kappa-B (NFKB)	TTSXVID	NFKB1_HUMAN; NFKB2_HUMAN; TF65_HUMAN; RELB_HUMAN; REL_HUMAN	Activator	[10]

Sulfasalazine Interacts with 4 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[11]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[12]
Peptide transporter 1 (SLC15A1)	DT9G7XN	S15A1_HUMAN	Substrate	[13]
Organic anion transporting polypeptide 2B1 (SLCO2B1)	DTPFTEQ	SO2B1_HUMAN	Substrate	[14]

Sulfasalazine Interacts with 12 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[15]
Azoreductase (azoR)	DE5CAX1	A0A074IU04_STRSL	Metabolism	[16]
Azoreductase (azoR)	DEGTKHL	T0VG26_9ENTE	Metabolism	[17]
Azoreductase (azoR)	DE3UF6Z	A0A0P0ETC6_BACT4	Metabolism	[17]
Azoreductase (azoR)	DE6GHJ5	A0A0P0ETC6_BACT4	Metabolism	[17]
Azoreductase (azoR)	DEEISQ2	AZOR_ENTFA	Metabolism	[16]
Azoreductase (azoR)	DEI2PC5	AZOR_CLOP1	Metabolism	[16]
Azoreductase (azoR)	DETEMAH	A0A349MYB4_9LACO	Metabolism	[17]
Azoreductase (azoR)	DEM1BHT	A0A132Z973_ENTFC	Metabolism	[16]
Azoreductase (azoR)	DEIKZOU	A0A0P0ETC6_BACT4	Metabolism	[18]
Azoreductase (azoR)	DENLBG3	A0A0P0ETC6_BACT4	Metabolism	[16]
Azoreductase (azoR)	DEIHK8V	A0A349MYB4_9LACO	Metabolism	[16]

Sulfasalazine Interacts with 33 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Decreases Methylation	[19]
Nuclear factor NF-kappa-B p105 subunit (NFKB1)	OTNRRD8I	NFKB1_HUMAN	Decreases Expression	[7]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Increases Activity	[20]
Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B)	OTQ4W7MT	TR11B_HUMAN	Increases Secretion	[21]
Tumor necrosis factor ligand superfamily member 11 (TNFSF11)	OTJEPKEQ	TNF11_HUMAN	Decreases Expression	[21]
Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB)	OT9RDS3H	IKKB_HUMAN	Decreases Expression	[22]
Transmembrane protease serine 2 (TMPRSS2)	OTN44YQ5	TMPS2_HUMAN	Increases Expression	[23]
25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial (CYP27B1)	OTTK98BH	CP27B_HUMAN	Decreases Expression	[24]
Apoptosis-inducing factor 1, mitochondrial (AIFM1)	OTKPWB7Q	AIFM1_HUMAN	Affects Localization	[25]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Increases Response To Substance	[26]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Decreases Expression	[27]
Glucocorticoid receptor (NR3C1)	OTCI2YDI	GCR_HUMAN	Increases Expression	[28]
Intercellular adhesion molecule 1 (ICAM1)	OTTOIX77	ICAM1_HUMAN	Decreases Expression	[8]
Insulin receptor (INSR)	OTTY341H	INSR_HUMAN	Increases Expression	[22]
Tropomyosin alpha-3 chain (TPM3)	OT5RU5G6	TPM3_HUMAN	Decreases Expression	[29]
Growth-regulated alpha protein (CXCL1)	OT3WCTZV	GROA_HUMAN	Affects Secretion	[30]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Decreases Expression	[27]
E-selectin (SELE)	OT33RZWY	LYAM2_HUMAN	Increases Expression	[31]
Thromboxane-A synthase (TBXAS1)	OTAXZJJ4	THAS_HUMAN	Decreases Activity	[32]
NF-kappa-B inhibitor alpha (NFKBIA)	OTFT924M	IKBA_HUMAN	Decreases Expression	[33]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[25]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Cleavage	[34]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Decreases Activity	[22]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Affects Localization	[25]
MHC class I polypeptide-related sequence A (MICA)	OTPEIEAR	MICA_HUMAN	Decreases Expression	[35]
Major histocompatibility complex class I-related gene protein (MR1)	OTZU3XX7	HMR1_HUMAN	Affects Expression	[36]
Proton-coupled folate transporter (SLC46A1)	OT049V7Y	PCFT_HUMAN	Decreases Activity	[37]
Angiotensin-converting enzyme 2 (ACE2)	OTTRZGU7	ACE2_HUMAN	Decreases Expression	[23]
Cystine/glutamate transporter (SLC7A11)	OTKJ6PXW	XCT_HUMAN	Decreases Activity	[38]
Arylamine N-acetyltransferase 2 (NAT2)	OTBPDQOY	ARY2_HUMAN	Increases Acetylation	[39]
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Increases ADR	[40]
Myeloperoxidase (MPO)	OTOOXLIN	PERM_HUMAN	Increases ADR	[40]
Methylenetetrahydrofolate reductase (MTHFR)	OTUBJSR7	MTHR_HUMAN	Increases Response To Substance	[41]

Indication(s) of Loperamide

Disease Entry	ICD 11	Status	REF
Diarrhea	ME05.1	Approved	[2]
Traveler's diarrhea	ME05.1	Approved	[5]
Middle East Respiratory Syndrome (MERS)	1D64	Preclinical	[6]
Severe acute respiratory syndrome (SARS)	1D65	Preclinical	[6]

Loperamide Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Opioid receptor delta (OPRD1)	TT27RFC	OPRD_HUMAN	Binder	[42]

Loperamide Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[43]

Loperamide Interacts with 5 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[44]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[45]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[45]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[45]
Oxygen-insensitive NADPH nitroreductase A (nfsA)	DEDPI65	NFSA_ECOLI	Metabolism	[46]

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