Drug Information

Drug (ID: DG00762) and It's Reported Resistant Information

• Name: Ketorolac
• Synonyms: Ketorolac; 74103-06-3; 5-Benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid; Ketorolaco; Ketorolacum [Latin]; Ketorolaco [Spanish]; Ketoralac; Ketorolacum; Macril; (+-)-Ketorolac; 66635-83-4; Acular; rac-ketorolac; RS 37619; (+)-Ketorolac; Toradol (TN); (+-)-5-Benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid; CHEBI:76223; Acuvail; MFCD00864281; RS37619; 1H-Pyrrolizine-1-carboxylic acid, 2,3-dihydro-5-benzoyl-, (+-)-; 5-(phenylcarbonyl)-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid; Ketorolac [INN:BAN]; SPRIX; RS-37619; Ketorolac (INN); rac Ketorolac-[d4]; 1H-Pyrrolizine-1-carboxylic acid, 5-benzoyl-2,3-dihydro-; NCGC00185990-01; CHEMBL469; SCHEMBL14891; MLS006011844; CHEBI:6129; GTPL6661; DTXSID8023189; BDBM85511; HMS3604J05; HMS3884M04; HY-B0580; AC-545; HTS001246; s1646; STL018674; AKOS005657203; AC-1121; CCG-204762; DB00465; KS-5175; SDCCGSBI-0050655.P004; NCGC00185990-02; NCGC00185990-05; NCGC00185990-15; K262; SMR001550090; SY107530; SBI-0050655.P003; CAS_74103-07-4; DB-011403; AB00053682; FT-0653523; FT-0670664; FT-0670665; FT-0670666; C07062; D08104; F16555; J10261; AB00053682-12; AB00053682-14; AB00053682_15; AB00053682_16; 635K834; A934549; Q2014797; BRD-A40639672-234-05-7; BRD-A40639672-234-09-9; KETOROLAC, ketorolactromethamine, Ketorolac Tromethamine; 5-(benzoyl)-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid; 5-Benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid #; rac-5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid; (1RS)-5-Benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid; (.+/-.)-2,3-Dihydro-5-benzoyl-1H-pyrrolizine-1-carboxylic acid; (.+/-.)-5-Benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid; 5-benzoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid; 1H-Pyrrolizine-1-carboxylic acid, 2,3-dihydro-5-benzoyl-, (.+/-.)-; 5-BENZOYL-2,3-DIHYDRO-1H-PYRROLO[1,2-A]PYRROLE-1-CARBOXYLIC ACID
• Indication:
  In total 1 Indication(s)
  Postoperative inflammation [ICD-11: 1A00-CA43]; Approved; [1]
• Target: Prostaglandin G/H synthase (COX); PGH1_HUMAN PGH2_HUMAN; [1]
• Formula: C15H13NO3
• IsoSMILES: C1CN2C(=CC=C2C(=O)C3=CC=CC=C3)C1C(=O)O
• InChI: 1S/C15H13NO3/c17-14(10-4-2-1-3-5-10)13-7-6-12-11(15(18)19)8-9-16(12)13/h1-7,11H,8-9H2,(H,18,19)
• InChIKey: OZWKMVRBQXNZKK-UHFFFAOYSA-N
• PubChem CID: 3826
• ChEBI ID: CHEBI:76223
• TTD Drug ID: D0D9JW
• INTEDE ID: DR0908
• DrugBank ID: DB00465

Type(s) of Resistant Mechanism of This Drug

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Acute myeloid leukemia [ICD-11: 2A60]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [1]

• Sensitive Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Acute myeloid leukemia [ICD-11: 2A60]
• The Specified Disease: Acute myelocytic leukemia
• The Studied Tissue: Bone marrow
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 4.70E-06; Fold-change: 9.31E-02; Z-score: 4.63E+00
• Experimental Note: Discovered Using In-vivo Testing Model
• Experiment for Molecule Alteration: Efflux pump genes expression analysis
• Mechanism Description: Ketorolac-fluconazole in vitro combination would be a promising strategy for further clinical in vivo trials to overcome fluconazole resistance in AML patients on induction chemotherapy. To our knowledge, the current study is the first in vitro report on the use of ketorolac in reverting fluconazole resistance in C. albicans isolated from AML patients. Resistance of C. albicans to azole antifungals is associated with overexpression of efflux pump genes especially CDR1 and MDR1.

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa_circ_0001946 [1]

• Sensitive Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• Experiment for Molecule Alteration: Efflux pump genes expression analysis
• Mechanism Description: Ketorolac-fluconazole in vitro combination would be a promising strategy for further clinical in vivo trials to overcome fluconazole resistance in AML patients on induction chemotherapy. To our knowledge, the current study is the first in vitro report on the use of ketorolac in reverting fluconazole resistance in C. albicans isolated from AML patients. Resistance of C. albicans to azole antifungals is associated with overexpression of efflux pump genes especially CDR1 and MDR1.

ICD-01: Infectious/parasitic diseases

Staphylococcal or streptococcal diseases [ICD-11: 1B5Z]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Biofilms [2]

• Sensitive Disease: staphylococcal infection [ICD-11: 1B5Z]
• Molecule Alteration: .; .
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: S. aureus ATCC 12600, L1101; 5833
• In Vitro Model: S. epidermidis ATCC 35984, L1116; 5833
• Experiment for Molecule Alteration: Gene expression analysis
• Experiment for Drug Resistance: Susceptibility testing; Adherent bacteria count assay; MBEC assay; Scanning electron microscopy assay; Membrane fluidity assay
• Mechanism Description: Gentamicin-ketorolac (GS-KT) combination demonstrated synergistic antibacterial action against planktonic Staphylococci. Control and clinical strains showed distinct biofilm growth dynamics and an increase in biofilm maturity was shown to confer further resistance to gentamicin for both 'low-risk' and 'high-risk' biofilms. The addition of ketorolac enhanced the antibiofilm activity of gentamicin against acquired resistance in staphylococcal biofilms. Mechanistic studies revealed that the synergistic action of gentamicin-ketorolac interferes with biofilm morphology and subverts bacterial stress response altering bacterial physiology, membrane dynamics, and biofilm properties.

References

• Ref 1: Ketorolac-fluconazole: A New Combination Reverting Resistance in Candida albicans from Acute Myeloid Leukemia Patients on Induction Chemotherapy: In vitro Study .J Blood Med. 2021 Jun 15;12:465-474. doi: 10.2147/JBM.S302158. eCollection 2021. 10.2147/JBM.S302158
• Ref 2: Synergistic use of anti-inflammatory ketorolac and gentamicin to target staphylococcal biofilms. J Transl Med. 2024 Jan 25;22(1):102.