Darbufelone mesylate is a dual inhibitor of cellular prostaglandin and leukotriene production. Darbufelone potently inhibits PGHS-2 (IC50 = 0.19 uM) but is much less potent with PGHS-1 (IC50= 20 uM). Darbufelone is a dual inhibitor of cellular PGF2R and LTB4 production. Darbufelone is orally active and nonulcerogenic in animal models of inflammation and arthritis. Darbufelone mesylate was in phase III clinical trials by Pfizer and Zhuhai United Laboratories for the treatment of rheumatoid arthritis.

Cimicoxib is a selective cyclooxygenase 2 inhibitor used in veterinary medicine to treat dogs for pain and inflammation associated with osteoarthritis and for the management of pain and inflammation associated with surgery. Limited data are available on cimicoxib, with one study documenting non-inferiority compared to carprofen in managing postoperative pain for dogs undergoing either orthopedic or soft tissue surgery. There are some data available as part of cimicoxib’s approval process in Europe to support its use for chronic pain.

Demethoxycurcumin is a derivative or curcumin and represents one of the major active components of curcumin products isolated from Curcumae sp. In preclinical models, Demethoxycurcumin inhibits LPS-induced nitric oxide (NO) production, and expression of iNOS and COX2 in RAW264.7 cells by blocking NF-kB activation. Demethoxycurcumin also inhibits NF-kB dependent iNOS, TNFα and IL-1β expression in LPS-treated rat microglial cells. Demethoxycurcumin suppresses the expression of MMPs and ICAM-1 in MDA-MB-231 human breast cancer cells by inhibition of NF-kB. Demethoxycurcumin is currently in Phase I clinical trials.

GW406381 is an investigational, highly selective cyclooxygenase-2 (COX-2) inhibitor for inflammatory pain treatment. It showed effectiveness in animal models of central sensitization such as chronic constriction injury and capsaicin-induced hyperalgesia. It's effect was also evaluated in several clinical trials in patients with peripheral nerve injury (Phase I ), rheumatoid arthritis (Phase III), the signs and symptoms of osteoarthritis of the knee to control of pain and improvement in function (Phase III), and in treating the signs and symptoms of dental pain following third molar tooth extraction (Phase III). Possessing favourable pharmacokinetic profiles and analgesic activity in vivo, GW406381 have also demonstrated relatively high brain penetration in the rat compared with the clinically available compounds, which may ultimately prove beneficial in the treatment of pain.

Apricoxib, (CS-706, 1) 2-(4-ethoxyphenyl)-4-methyl-1-(4-sulfamoylphenyl)-pyrrole, a small-molecule, orally active, selective COX-2 inhibitor was discovered by investigators at Daiichi Sankyo in 1996. Apricoxib binds to and inhibits the enzyme cyclooxygenase-2 (COX-2), thereby inhibiting the conversion of arachidonic acid into prostaglandins. Apricoxib-mediated inhibition of COX-2 may induce tumor cell apoptosis and inhibit tumor cell proliferation and tumor angiogenesis. COX-related metabolic pathways may represent crucial regulators of cellular proliferation and angiogenesis. Clinical studies demonstrated potent analgesic activity and preclinical studies demonstrated good pharmacokinetics, pharmacodynamics and gastrointestinal tolerability. As an anticancer agent, preclinical studies demonstrated efficacy in biliary tract cancer models and colorectal carcinoma. Phase IIa trial data indicated that apricoxib was a potent analgesic in the treatment of pain in postoperative dental surgery. Apricoxib, a novel once-daily selective cyclooxygenase-2 inhibitor, was investigated in combination with erlotinib for recurrent stage IIIB/IV nonsmall cell lung cancer. Apricoxib plus erlotinib was well tolerated and yielded a 60% disease control rate. A phase II trial was investigating 400 mg/day apricoxib plus 150 mg/day erlotinib in patients selected based on change in urinary PGE-M. However, in 2015 development was abandoned due to poor clinical trial results.

Ampyrone (4-Aminoantipyrine or AAP) is a metabolite of aminophenazone and is an aromatic substance with analgesic, antipyretic and anti-inflammatory properties. When combined with the antineoplastic agents, ampyrone decreased their genotoxic, mutagenic, apoptotic, and phagocytic effects. However, ampyrone usually produces side effects, such as the risk of agranulocytosis. Although ampyrone is scarcely ever administered as an analgesic because of the potential side effects, as a raw material, it is mostly used to produce ampyrone derivatives, which have better biological activities. In addition, it is used as a reagent for biochemical reactions producing peroxides or phenols and can also be used to detect phenols in the environment. Exposure to ampyrone could induce changes in the enzyme catalase structure and function.

Chrysophanic acid (Chrysophanol) is a member of the anthraquinone family abundant in rhubarb, a widely used herb for obesity treatment in Traditional Korean Medicine. Chrysophanol has been shown to induce cell death in different types of cancer cells. Chrysophanol inhibits EGF-induced phosphorylation of EGFR and suppresses activation of AKT and mTOR/p70S6K. Chrysophanol also effectively suppresses breast cancer cell proliferation and facilitates chemosentivity through modulation of the NF-κB signaling pathway. A treatment of chrysophanol could reduce significantly the clinical signs and the levels of inflammatory mediators in a colitis model caused by DSS treatment. The anti-inflammatory activities of chrysophanol could be attributed, at least in part, to the inhibition of proinflammatory cytokine production (TNF-α and IL-6), COX-2, and iNOS protein expression. These effects of chrysophanol are caused by the inhibition of LPS-induced NF-κB activation, IκB-α degradation, and caspase-1 activation. These results provide experimental evidence showing that chrysophanol might prove useful in the treatment of inflammatory diseases.