Drug Information

Drug (ID: DG00404) and It's Reported Resistant Information

• Name: Probenecid
• Synonyms: Apurina; Bencid; Benecid; Benemid; Benemide; Benuryl; Panuric; Parabenem; Probalan; Probampacin; Probecid; Proben; Probenecida; Probenecide; Probenecidum; Probenemid; Probenicid; Probenid; Probexin; Prolongine; Robenecid; Sulprin; Tubophan; Uricosid; Urocid; Biokanol Brand of Probenecid; ICN Brand of Probenecid; IDIS Brand of Probenecid; Major Brand of Probenecid; Martec Brand of Probenecid; Merck Brand of Probenecid; Ophthalmic Brand of Probenecid; Parmed Brand of Probenecid; Probenecid Major Brand; Probenecid Martec Brand; Probenecid Parmed Brand; Probenecid Weimer; Probenecid Zenith Brand; Probenecid acid; Synergid R; Valdecasas Brand of Probenecid; Zenith Brand of Probenecid; Benemid (TN); Benuryl (TN); Col-BENEMID; ColBenemid (co mponent of); ColBenemid (component of); P-[Dipropylsulfamoyl]benzoic acid; Polycillin-BRB; Pro-Cid; Probenecida [INN-Spanish]; Probenecide [INN-French]; Probenecidum [INN-Latin]; P-(Dipropylsulfamoyl)benzoic acid; P-(Dipropylsulfamyl)benzoic acid; Polycillin-PRB (component of); Probenecid [INN:BAN:JAN]; Probenecid (JP15/USP/INN); 4-((Dipropylamino)sulfonyl)benzoic acid;4-(Di-n-propylsulfamoyl)benzoesaeure; 4-(Dipropylsulfamoyl)benzoic acid; 4-(N,N-Dipropylsulfamoyl)benzoesaeure; 4-[(dipropylamino)sulfonyl]benzoic acid
• Indication:
  In total 2 Indication(s)
  Gout [ICD-11: FA25]; Approved; [1]
  Inborn purine/pyrimidine/nucleotide metabolism error [ICD-11: 5C55]; Approved; [1]
• Target: Solute carrier family 22 member 8 (SLC22A8); S22A8_HUMAN; [1]
• Formula: C13H19NO4S
• IsoSMILES: CCCN(CCC)S(=O)(=O)C1=CC=C(C=C1)C(=O)O
• InChI: 1S/C13H19NO4S/c1-3-9-14(10-4-2)19(17,18)12-7-5-11(6-8-12)13(15)16/h5-8H,3-4,9-10H2,1-2H3,(H,15,16)
• InChIKey: DBABZHXKTCFAPX-UHFFFAOYSA-N
• PubChem CID: 4911
• ChEBI ID: CHEBI:8426
• TTD Drug ID: D0L7FM
• VARIDT ID: DR00232
• INTEDE ID: DR1341
• DrugBank ID: DB01032

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-02: Benign/in-situ/malignant neoplasm

Prostate cancer [ICD-11: 2C82]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ATP-binding cassette sub-family C2 (ABCC2) [1]

• Molecule Alteration: Expression; Up-regulation
• Sensitive Disease: Prostate cancer [ICD-11: 2C82.0]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell autophagy; Inhibition; hsa04140
• Cell Pathway Regulation: Cell cytotoxicity; Activation; hsa04650
• In Vitro Model: PC3 cells; Prostate; Homo sapiens (Human); CVCL_0035
• In Vitro Model: 22RV1 cells; Prostate; Homo sapiens (Human); CVCL_1045
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: However, probenecid only weakly inhibits ABCG2. Thus, probenecid enhanced the efficacy of anticancer drugs against 22Rv1 spheroids by inhibiting drug resistance-related transporters such as MRP; at high probenecid concentrations, the chemosensitization effect may be reduced owing to promotion of alternate drug excretion pathways via upregulated ABCG2 expression.

Key Molecule: Multidrug resistance-associated protein 1 (MRP1) [1]

• Molecule Alteration: Expression; Down-regulation
• Sensitive Disease: Prostate cancer [ICD-11: 2C82.0]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell colony; Inhibition; hsa05200
• In Vitro Model: PC3 cells; Prostate; Homo sapiens (Human); CVCL_0035
• In Vitro Model: 22RV1 cells; Prostate; Homo sapiens (Human); CVCL_1045
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: However, probenecid only weakly inhibits ABCG2. Thus, probenecid enhanced the efficacy of anticancer drugs against 22Rv1 spheroids by inhibiting drug resistance-related transporters such as MRP; at high probenecid concentrations, the chemosensitization effect may be reduced owing to promotion of alternate drug excretion pathways via upregulated ABCG2 expression.

References

• Ref 1: Pleiotropic effects of probenecid on three-dimensional cultures of prostate cancer cells. Life Sci. 2021 Aug 1;278:119554. doi: 10.1016/j.lfs.2021.119554. Epub 2021 Apr 28.