Details of the Drug Combination

General Information of Drug Combination (ID: DCD8TNG)

• Drug Combination Name: Celecoxib + Sulfasalazine
• Indication: Ankylosing Spondylitis; Status: Phase 4 [1]
• Component Drugs:
  Celecoxib (DM6LOQU): Small molecular drug
  Sulfasalazine (DMICA9H): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Celecoxib

Disease Entry	ICD 11	Status	REF
Dysmenorrhea	GA34.3	Approved	[2]
Lung cancer	2C25.0	Approved	[2]
Osteoarthritis	FA00-FA05	Approved	[2]
Rheumatoid arthritis	FA20	Approved	[3]
Pain	MG30-MG3Z	Phase 3	[3]
Colon cancer	2B90.Z	Investigative	[2]
Familial adenomatous polyposis	2B90.Y	Investigative	[2]
Precancerous condition	N.A.	Investigative	[2]

Celecoxib 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	Inhibitor	[7]

Celecoxib Interacts with 5 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[8]
Sulfotransferase 1A1 (SULT1A1)	DEYWLRK	ST1A1_HUMAN	Metabolism	[9]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[10]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[11]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[12]

Indication(s) of Sulfasalazine

Disease Entry	ICD 11	Status	REF
Irritable bowel syndrome	DD91.0	Approved	[4]
Rheumatoid arthritis	FA20	Approved	[5]
Ulcerative colitis	DD71	Approved	[6]

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	[15]
Nuclear factor NF-kappa-B (NFKB)	TTSXVID	NFKB1_HUMAN; NFKB2_HUMAN; TF65_HUMAN; RELB_HUMAN; REL_HUMAN	Activator	[16]

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	[17]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[18]
Peptide transporter 1 (SLC15A1)	DT9G7XN	S15A1_HUMAN	Substrate	[19]
Organic anion transporting polypeptide 2B1 (SLCO2B1)	DTPFTEQ	SO2B1_HUMAN	Substrate	[20]

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	[21]
Azoreductase (azoR)	DE5CAX1	A0A074IU04_STRSL	Metabolism	[22]
Azoreductase (azoR)	DEGTKHL	T0VG26_9ENTE	Metabolism	[23]
Azoreductase (azoR)	DE3UF6Z	A0A0P0ETC6_BACT4	Metabolism	[23]
Azoreductase (azoR)	DE6GHJ5	A0A0P0ETC6_BACT4	Metabolism	[23]
Azoreductase (azoR)	DEEISQ2	AZOR_ENTFA	Metabolism	[22]
Azoreductase (azoR)	DEI2PC5	AZOR_CLOP1	Metabolism	[22]
Azoreductase (azoR)	DETEMAH	A0A349MYB4_9LACO	Metabolism	[23]
Azoreductase (azoR)	DEM1BHT	A0A132Z973_ENTFC	Metabolism	[22]
Azoreductase (azoR)	DEIKZOU	A0A0P0ETC6_BACT4	Metabolism	[24]
Azoreductase (azoR)	DENLBG3	A0A0P0ETC6_BACT4	Metabolism	[22]
Azoreductase (azoR)	DEIHK8V	A0A349MYB4_9LACO	Metabolism	[22]

Sulfasalazine Interacts with 13 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	[25]
Nuclear factor NF-kappa-B p105 subunit (NFKB1)	OTNRRD8I	NFKB1_HUMAN	Decreases Expression	[13]
Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B)	OTQ4W7MT	TR11B_HUMAN	Increases Secretion	[26]
Tumor necrosis factor ligand superfamily member 11 (TNFSF11)	OTJEPKEQ	TNF11_HUMAN	Decreases Expression	[26]
25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial (CYP27B1)	OTTK98BH	CP27B_HUMAN	Decreases Expression	[27]
Apoptosis-inducing factor 1, mitochondrial (AIFM1)	OTKPWB7Q	AIFM1_HUMAN	Affects Localization	[28]
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	[31]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Decreases Activity	[32]
MHC class I polypeptide-related sequence A (MICA)	OTPEIEAR	MICA_HUMAN	Decreases Expression	[33]
Major histocompatibility complex class I-related gene protein (MR1)	OTZU3XX7	HMR1_HUMAN	Affects Expression	[34]
Arylamine N-acetyltransferase 2 (NAT2)	OTBPDQOY	ARY2_HUMAN	Increases Acetylation	[35]

References

• [1] ClinicalTrials.gov (NCT02638896) Dose Reduction of Etanercept in Patients With Ankylosing Spondylitis
• [2] Celecoxib FDA Label
• [3] 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: 2892).
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [5] 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: 4840).
• [6] Sulfasalazine FDA Label
• [7] Pfizer. Product Development Pipeline. March 31 2009.
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• [27] Down-regulation by nuclear factor kappaB of human 25-hydroxyvitamin D3 1alpha-hydroxylase promoter. Mol Endocrinol. 2004 Oct;18(10):2440-50. doi: 10.1210/me.2002-0441. Epub 2004 Jul 8.
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