Repositioning Candidate Details

Candidate ID: R0157
Source ID: DB00465
Source Type: approved
Compound Type: small molecule
Compound Name: Ketorolac
Synonyms: rac-Ketorolac
Molecular Formula: C15H13NO3
SMILES: OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1
Structure:
DrugBank Description: Ketorolac is a Non-steroidal anti-inflammatory drug (NSAID) and is commercially available as an oral tablet, injectable, nasal spray and as an ophthalmic solution. It's analgesic properties make it a useful pain management tool across many settings including postoperative pain, rheumatoid arthritis, osteoarthritis, menstrual disorders, headaches, spinal and soft tissue pain, and ankylosing spondylitis. Impressively, ketorolac has a similar efficacy to standard doses of morphine and meperidine making it a useful opioid sparing agent.
CAS Number: 74103-06-3
Molecular Weight: 255.2686
DrugBank Indication: Ketorolac is a Non-steroidal anti-inflammatory drug (NSAID) and has antipyretic, analgesic and anti-inflammatory properties. It is indicated for short term management of acute pain that requires the calibre of pain management offered by opioids. Clinicians may choose to initiate ketorolac to manage post-operative pain, spinal and soft tissue pain, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, menstrual disorders and headaches among other ailments. Regardless of the etiology of pain, patients should use the lowest possible dose, and avoid using ketorolac for an extended period of time (ideally ≤ 5 days). A benefit of choosing ketorolac over other analgesics with similar potency is that that there does not appear to be a risk of dependence or tolerance with ketorolac use.
DrugBank Pharmacology: Ketorolac is a non-selective NSAID and acts by inhibiting both COX-1 and COX-2 enzymes which are normally responsible for converting arachidonic acid to prostaglandins. The COX-1 enzyme is constitutively active and can be found in platelets, gastric mucosa, and vascular endothelium. On the other hand, the COX-2 enzyme is inducible and mediates inflammation, pain and fever. As a result, inhibition of the COX-1 enzyme is linked to an increased risk of bleeding and risk of gastric ulceration, while the desired anti-inflammatory and analgesic properties are linked to inhibition of the COX-2 enzyme. Therefore, despite it's effectiveness in pain management, ketorolac should not be used long-term since this increases the risk of serious adverse effects such as gastrointestinal bleeding, peptic ulcers, and perforations.
DrugBank MoA: Ketorolac inhibits key pathways in prostaglandin synthesis which is crucial to it's mechanism of action. Although ketorolac is non-selective and inhibits both COX-1 and COX-2 enzymes, it's clinical efficacy is derived from it's COX-2 inhibition. The COX-2 enzyme is inducible and is responsible for converting arachidonic acid to prostaglandins that mediate inflammation and pain. By blocking this pathway, ketorolac achieves analgesia and reduces inflammation. Ketorolac is administered as a racemic mixture; however, the "S" enantiomer is largely responsible for it's pharmacological activity.
Targets: Prostaglandin G/H synthase 2 inhibitor; Prostaglandin G/H synthase 1 inhibitor
Inclusion Criteria: Therapeutic strategy associated

Strategy ID Strategy Synonyms Related Targets Related Drugs
S05 Anti-inflammatory inflammatory Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; Details

Target ID Target Name GENE Action Class UniProtKB ID Entry Name

Diseases ID DO ID Disease Name Definition Class
I15 1290 Bone disease A connective tissue disease that affects the structure or development of bone or causes an impairment of normal bone function. http://en.wikipedia.org/wiki/Bone_disease disease of anatomical entity/ musculoskeletal system disease/connective tissue disease Details