Expert opinion on investigational drugs
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Expert Opin Investig Drugs · Feb 2008
ReviewCelecoxib analogs that lack COX-2 inhibitory function: preclinical development of novel anticancer drugs.
Celecoxib is an NSAID that was developed as a selective inhibitor of COX-2 and approved by the FDA for the treatment of various forms of arthritis and the management of acute or chronic pain. In addition, it was more recently approved as an oral adjunct to prevent colon cancer development in patients with familial adenomatous polyposis and is presently being investigated for its chemotherapeutic potential in the therapy of advanced cancers. However, in laboratory studies it was discovered that celecoxib was able to suppress tumor growth in the absence of any apparent involvement of COX-2, and additional pharmacologic activities associated with this drug were found. ⋯ This dualism enabled the synthesis of close structural analogs of celecoxib that exhibited increased antitumor potency in the absence of COX-2 inhibition. In theory, such compounds should be superior to celecoxib for antitumor purposes because they might reduce gastrointestinal and cardiovascular risks and the life-threatening side effects that appear during the long-term use of selective COX-2 inhibitors. In this review, the authors present the status of preclinical development of anticancer analogs of celecoxib that are COX-2 inactive, with an emphasis on 2,5-dimethyl-celecoxib (DMC) and OSU-03012.