Drug Information

Drug (ID: DG00039) and It's Reported Resistant Information

• Name: Sulfasalazine
• Synonyms: Sulfasalazine; 599-79-1; Salicylazosulfapyridine; Salazosulfapyridine; Azulfidine; Asulfidine; Salazopyridin; Sulcolon; Azopyrin; Accucol; Colo-Pleon; Salazopiridazin; Salisulf; Reupirin; Benzosulfa; Azopyrine; Salazosulfapyridin; Sulfasalazina; w-t Sasp oral; Sulfasalazinum; Sulfasalazin; Azulfidine EN; Sulfazalazine; Azulfidine EN-tabs; Salazosulfapiridina; Sas-500; Salazosulfapyridinum; Azosulfidin; SASP; Salazo-sulfapyridinum; 5-(p-(2-Pyridylsulfamyl)phenylazo)salicylic acid; SAS-500; Sulfasalizine
• Indication:
  In total 2 Indication(s)
  Irritable bowel syndrome [ICD-11: DD91]; Approved; [1]
  Rheumatoid arthritis [ICD-11: FA20]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Rheumatoid arthritis [ICD-11: FA20]; [2]
• Target: ATP-binding cassette transporter G2 (ABCG2); ABCG2_HUMAN; [1]
• Target: Nuclear factor NF-kappa-B (NFKB); NFKB1_HUMAN NFKB2_HUMAN TF65_HUMAN RELB_HUMAN REL_HUMAN; [1]
• Formula: C18H14N4O5S
• IsoSMILES: C1=CC=NC(=C1)NS(=O)(=O)C2=CC=C(C=C2)N=NC3=CC(=C(C=C3)O)C(=O)O
• InChI: 1S/C18H14N4O5S/c23-16-9-6-13(11-15(16)18(24)25)21-20-12-4-7-14(8-5-12)28(26,27)22-17-3-1-2-10-19-17/h1-11,23H,(H,19,22)(H,24,25)
• InChIKey: NCEXYHBECQHGNR-UHFFFAOYSA-N
• PubChem CID: 5339
• ChEBI ID: CHEBI:9334
• TTD Drug ID: D02ZTJ
• VARIDT ID: DR00201
• INTEDE ID: DR1513
• DrugBank ID: DB00795

Type(s) of Resistant Mechanism of This Drug

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-13: Digestive system diseases

Ulcerative colitis [ICD-11: DD71]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ATP-binding cassette sub-family G2 (ABCG2) [1]

• Molecule Alteration: Expression; Down-regulation
• Sensitive Disease: Ulcerative colitis [ICD-11: DD71.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: CaCo2 cells; Colon; Homo sapiens (Human); CVCL_0025
• In Vitro Model: IPS cells; Colon; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: Ussing chamber system assay
• Mechanism Description: Digoxin and fexofenadine (each 5 uM) were selected as P-gp substrates, and sulfasalazine and rosuvastatin (each 5 uM) were selected as BCRP substrates to evaluate the efflux transport mediated by P-gp and BCRP. PSC833 (15 uM) and ko143 (15 uM) were used as typical inhibitors of P-gp and BCRP, respectively. Serosal-to-mucosal transport of all the tested P-gp and BCRP substrate drugs was significantly decreased or tended to decrease in the presence of P-gp/BCRP inhibitor cocktail.

ICD-15: Musculoskeletal/connective-tissue diseases

Rheumatoid arthritis [ICD-11: FA20]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ATP-binding cassette sub-family G2 (ABCG2) [2]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Rheumatoid arthritis [ICD-11: FA20.0]
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: MTX is a substrate for eight ABC transporters. In vitro studies demonstrated that RAFLS treated with MTX had higher ABCB1 expression levels than controls, with a positive correlation between ABCB1 expression levels and RA treatment duration. In addition to MTX, other DMARDs (e.g. sulfasalazine, leflunomide, bucillamine, azathioprine), glucocorticoids (e.g. betamethasone, dexamethasone), and NSAIDs (e.g. celecoxib and indomethacin) are also substrates of ABC transporters.

References

• Ref 1: Characterization of the Human Intestinal Drug Transport with Ussing Chamber System Incorporating Freshly Isolated Human Jejunum. Drug Metab Dispos. 2021 Jan;49(1):84-93. doi: 10.1124/dmd.120.000138. Epub 2020 Oct 21.
• Ref 2: Drug-resistance in rheumatoid arthritis: the role of p53 gene mutations, ABC family transporters and personal factors .Curr Opin Pharmacol. 2020 Oct;54:59-71. doi: 10.1016/j.coph.2020.08.002. Epub 2020 Sep 14. 10.1016/j.coph.2020.08.002