Sulindac is a nonsteroidal anti-inflammatory agent (NSAIA) of the arylalkanoic acid class that is marketed in the U.S. by Merck as Clinoril. Like other NSAIAs, it may be used in the treatment of acute or chronic inflammatory conditions. Sulindac is a prodrug, derived from sulfinylindene, that is converted in vivo to an active sulfide compound by liver enzymes. The sulfide metabolite then undergoes enterohepatic circulation; it is excreted in the bile and then reabsorbed from the intestine. This is thought to help maintain constant blood levels with reduced gastrointestinal side effects. Some studies have shown sulindac to be relatively less irritating to the stomach than other NSAIA's except for drugs of the cyclooxygenase-2 (COX-2) inhibitor class. The exact mechanism of its NSAIA properties is unknown, but it is thought to act on enzymes COX-1 and COX-2, inhibiting prostaglandin synthesis.

Exisulind (tentative trade name Aptosyn) is an antineoplastic agent, which was originally developed by Cell Pathways. This drug is an inhibitor of phosphodiesterase (PDE) isozymes: PDE5 and PDE4. Inhibition of PDE5 appears to be pharmacologically relevant, which leads to increase cGMP and activate protein kinase G at doses that induce apoptosis, whereas cyclic AMP levels were not changed. Exisulind has been in phase III clinical trials for the treatment of Non-Small Cell Lung Cancer and for the treatment of polyps in patients who have familial adenomatous polyposis (Colorectal Cancer and Small Intestine Cancer). In addition, this drug was in phase II/III for the treatment of Prostate Cancer, however, there studies have been discontinued.

Sulindac sulfide, an active metabolite of the nonsteroidal anti-inflammatory drug (NSAID) sulindac, directly binds to the Ras gene product p21ras in a non-covalent manner. Sulindac sulfide strongly inhibits Ras-induced malignant transformation and Ras/Raf dependent transactivation, due to its action at the most critical site in Ras signaling. Sulindac sulfide was proposed as a lead compound in the search for novel anti-cancer drugs, which directly inhibit Ras-mediated cell proliferation and malignant transformation. Experiments on rodents have revealed that sulindac sulfide effectively inhibited tumor growth in colorectal cancer cell xenografts mice. In addition, was shown, that sulindac sulfide inhibited ABCC1-mediated transport of appropriate endogenous and xenobiotic substrates. The drug was selectivity for ABCC1 as compared with ABCB1 and ABCG2. These properties allow designing novel ABCC1 inhibitors by chemically modifying sulindac sulfide to improve potency and selectivity to inhibit ABCC1-mediated efflux for preventing drug resistance and tumor recurrence or secondary tumor formation following chemotherapy.