| Candidate ID: | R0165 |
| Source ID: | DB00482 |
| Source Type: | approved; investigational |
| Compound Type: |
small molecule
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| Compound Name: |
Celecoxib
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| Synonyms: |
p-(5-p-Tolyl-3-(trifluoromethyl)pyrazol-1-yl)benzenesulfonamide
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| Molecular Formula: |
C17H14F3N3O2S
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| SMILES: |
CC1=CC=C(C=C1)C1=CC(=NN1C1=CC=C(C=C1)S(N)(=O)=O)C(F)(F)F
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| Structure: |
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| DrugBank Description: |
Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is a nonsteroidal anti-inflammatory drug (NSAID) which is known for its decreased risk of causing gastrointestinal bleeding compared to other NSAIDS. It is used to manage symptoms of various types of arthritis pain and in familial adenomatous polyposis (FAP) to reduce precancerous polyps in the colon. It is marketed by Pfizer under the brand name Celebrex, and was initially granted FDA approval in 1998.
Interestingly, selective COX-2 inhibitors (especially celecoxib), have been evaluated as potential cancer chemopreventive and therapeutic drugs in clinical trials for a variety of malignancies.
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| CAS Number: |
169590-42-5
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| Molecular Weight: |
381.372
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| DrugBank Indication: |
Celecoxib is indicated for symptomatic treatment of adult osteoarthritis (OA) and adult rheumatoid arthritis (RA). Celecoxib is not a substitute for aspirin for cardiovascular event prophylaxis.
It may be also be used to treat acute pain from various sources, juvenile rheumatoid arthritis in children over 2, ankylosing spondylitis, and primary dysmenorrhea.
Celecoxib, in combination with , is indicated for the management of acute pain in adults severe enough to require an opioid analgesic and in whom alternative treatments are inadequate.
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| DrugBank Pharmacology: |
Celecoxib inhibits cyclooxygenase 2 (COX-2) enzyme, reducing pain and inflammation. It is important to note that though the risk of bleeding with celecoxib is lower than with certain other NSAIDS, it exists nonetheless and caution must be observed when it is administered to those with a high risk of gastrointestinal bleeding.
**A note on the risk of cardiovascular events**
Significant concerns regarding the safety of COX-2 selective NSAIDs emerged in the early 2000s. , another member of the COX-2 inhibitor drug class, also known as Vioxx, was withdrawn from the market due to prothrombotic cardiovascular risks. Following an FDA Advisory Committee meeting in 2005, in which data from large clinical outcome trials were evaluated, the FDA concluded that the risk for cardiovascular thrombotic events for both COX-2 selective NSAIDs and nonselective NSAIDs was evident. It was determined that the benefits of celecoxib treatment, however, outweighed the risks. Postmarketing cardiovascular outcomes trial (PRECISION) revealed that the lowest possible dose of celecoxib was similar in cardiovascular safety to moderate strength doses of both naproxen and ibuprofen. Patients who had previous cardiovascular events including acute MI, coronary revascularization, or coronary stent insertion were not evaluated in the trial. It is not advisable to administer NSAIDS to these groups of patients.
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| DrugBank MoA: |
Unlike most NSAIDs, which inhibit both types of cyclooxygenases (COX-1 and COX-2), celecoxib is a selective noncompetitive inhibitor of cyclooxygenase-2 (COX-2) enzyme. COX-2 is expressed heavily in inflamed tissues where it is induced by inflammatory mediators. The inhibition of this enzyme reduces the synthesis of metabolites that include prostaglandin E2 (PGE2), prostacyclin (PGI2), thromboxane (TXA2), prostaglandin D2 (PGD2), and prostaglandin F2 (PGF2). Resultant inhibition of these mediators leads to the alleviation of pain and inflammation.
By inhibiting prostaglandin synthesis, non-steroidal anti-inflammatory drugs (NSAIDs) cause mucosal damage, ulceration and ulcer complication throughout the gastrointestinal tract. Celecoxib poses less of an ulceration risk than other NSAIDS, owing to its decreased effect on gastric mucosal prostaglandin synthesis when compared to placebo.
Celecoxib exerts anticancer effects by binding to the cadherin-11 (CDH11)protein, which is thought to be involved in the progression of tumors, and inhibiting the 3-phosphoinositide-dependent kinase-1 (PDK-1) signaling mechanism. In addition, celecoxib has been found to inhibit carbonic anhydrase enzymes 2 and 3, further enhancing its anticancer effects.
As mentioned in the pharmacodynamics section of this drug entry, celecoxib may cause an increased risk of thrombotic events. The risk of thrombosis resulting from COX-2 inhibition is caused by the vasoconstricting actions of thromboxane A2, leading to enhanced platelet aggregation, which is uncontrolled when the actions of prostacyclin, a platelet aggregation inhibitor, are suppressed through the inhibition of COX-2.
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| Targets: |
Prostaglandin G/H synthase 2 inhibitor; 3-phosphoinositide-dependent protein kinase 1 inhibitor; Carbonic anhydrase 2 inhibitor; Carbonic anhydrase 3 inhibitor; Cadherin-11 inhibitor
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| Inclusion Criteria: |
Therapeutic strategy associated
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