Auranofin (brand name Ridaura) is an organogold compound classified by the World Health Organization as an antirheumatic agent. Ridaura is indicated in the management of adults with active classical or definite rheumatoid arthritis (ARA criteria) who have had an insufficient therapeutic response to, or are intolerant of, an adequate trial of full doses of one or more nonsteroidal anti-inflammatory drugs. The mechanism of action of is not understood. In patients with adult rheumatoid arthritis, it may modify disease activity as manifested by synovitis and associated symptoms, and reflected by laboratory parameters such as ESR. There is no substantial evidence, however, that gold-containing compounds induce remission of rheumatoid arthritis. It may act as an inhibitor of kappab kinase and thioredoxin reductase, which would lead to a decreased immune response and decreased free radical production, respectively. In patients with inflammatory arthritis, such as adult and juvenile rheumatoid arthritis, gold salts can decrease the inflammation of the joint lining. This effect can prevent destruction of bone and cartilage. Ridaura should be added to a comprehensive baseline program, including non-drug therapies. Unlike anti-inflammatory drugs, RIDAURA does not produce an immediate response. Therapeutic effects may be seen after three to four months of treatment, although improvement has not been seen in some patients before six months.

Ascorbic acid (vitamin C) is a water-soluble vitamin. It occurs as a white or slightly yellow crystal or powder with a slight acidic taste. Ascorbic acid is an electron donor, and this property accounts for all its known functions. As an electron donor, ascorbic acid is a potent water-soluble antioxidant in humans. Ascorbic acid acts as an antioxidant under physiologic conditions exhibiting a cross over role as a pro-oxidant in pathological conditions. Oxidized ascorbic acid (dehydroascorbic acid (DHA) directly inhibits IkappaBalpha kinase beta (IKKbeta) and IKKalpha enzymatic activity in vitro, whereas ascorbic acid did not have this effect. These findings define a function for vitamin C in signal transduction other than as an antioxidant and mechanistically illuminate how vitamin C down-modulates NF-kappaB signaling. Vitamin C is recommended for the prevention and treatment of scurvy. Its parenteral administration is desirable for patients with an acute deficiency or for those whose absorption of orally ingested ascorbic acid (vitamin c) is uncertain. Symptoms of mild deficiency may include faulty bone and tooth development, gingivitis, bleeding gums, and loosened teeth. Febrile states, chronic illness, and infection (pneumonia, whooping cough, tuberculosis, diphtheria, sinusitis, rheumatic fever, etc.) increase the need for ascorbic acid (vitamin c). Hemovascular disorders, burns, delayed fracture and wound healing are indications for an increase in the daily intake.

Bardoxolone methyl, the C-28 methyl ester of 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO) known as CDDO-Me or RTA 402, is one of the derivatives of synthetic triterpenoids. Bardoxolone methyl directly blocks IKKbeta activity and thereby the NF-kappaB pathway by interacting with Cys-179 in the IKKbeta activation loop. Binding of bardoxolone methyl to Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1 (Keap1) disrupts its critical cysteine residues, leading to the release of the nuclear factor erythroid 2-related factor 2 (Nrf2), which hinders its ubiquitination and finally leads to its stabilization and nuclear translocation. In the nucleus, Nrf2 activates the transcription of phase 2 response genes, leading to a coordinated antioxidant and anti-inflammatory response. In addition, it acts as an antagonist of the peroxisome proliferator-activated receptor gamma. Through Keap1/Nrf2 and nuclear factor-κB pathways, this agent can modulate the activities of a number of important proteins that regulate inflammation, redox balance, cell proliferation and programmed cell death. This agent is generally well tolerated, but it may increase adverse cardiovascular events. Presently, it is being further tested for the treatment of patients with chronic kidney disease, cancer, and pulmonary arterial hypertension.

MLN120B is a potent and selective inhibitor of IKK-beta, which competes with ATP at the ATP-binding site. MLN120B has been shown to be a promising treatment in preclinical models of rheumatoid arthritis, non-Hodgkin's lymphoma and multiple myeloma.

Bay 65-1942 free base (Bay 65-1942) is a selective inhibitor of IKKβ with IC50 value of 10 uM and Ki value of 2 nM. Bay 65-1942 has been reported to provide cardioprotection through specific suppression of NF-κB signaling. It also afforded potent neuroprotection against LPS-induced neurodegeneration through selective inhibition of NF-kappaB activation and may be of potential benefit in the treatment of PD.

Gamabufotalin belongs to bufadienolides was first isolated from B. formosus Boulenger and described by Kotake in 1928. Gamabufotalin is a component of traditional Chinese medicinal preparations containing ChanSu, also known as toad venom, a dried product of the skin and parotid venom glands from the Asiatic toad (Bufo gargarizans). Gamabufotalin inhibits sodium/potassium-transporting ATPase activity and exhibited positive inotropic action in the papillary muscle preparations. Gamabufotalin demonstrates significant anti-tumor activity in vitro on cancer cells and in vivo on mouse tumor xenografts. Gamabufotalin, a major derivative of bufadienolide, inhibits VEGF-induced angiogenesis.

BMS-345541 is a highly selective inhibitor of I kappa B kinase that binds at an allosteric site of the enzyme and blocks NF-kappa B-dependent transcription in mice. BMS-345541 was identified as a selective inhibitor of the catalytic subunits of IKK (IKK-2 IC(50) = 0.3 uM, IKK-1 IC(50) = 4 uM). A binding model is proposed in which BMS-345541 binds to similar allosteric sites on IKK-1 and IKK-2, which then affects the active sites of the subunits differently. BMS-345541 was shown to have excellent pharmacokinetics in mice, and peroral administration showed the compound to dose-dependently inhibit the production of serum tumor necrosis factor alpha following intraperitoneal challenge with lipopolysaccharide. BMS-345541 is effective against NF-kappa B activation in mice and represents an important tool for investigating the role of IKK in disease models. BMS-345541 blocks both joint inflammation and destruction in collagen-induced arthritis in mice.

Acetyl-β-boswellic acid (or 3-O-acetyl-β-BA or AβBA) is a cytotoxic compound, which can be isolated from the gum resins of various Boswellia species. It was studied the mechanism of action of this compound on prostate cancer cells and was revealed, that AβBA inhibits IκB kinase (IKK) activity, leading to subsequent inhibition of the antiapoptotic proteins Bcl-2 and Bcl-xL and also cyclin D1, a crucial regulator of cell proliferation. This mechanism finally promote apoptosis of the androgen-independent prostate cancer cells. In addition was shown, that AβBA directly interacts with the antimicrobial peptide LL-37. This binding resulted in an inhibition of the functionality of LL-37, that might be a relevant mechanism underlying the anti-inflammatory properties of AβBA and suggested this compound as suitable chemical tools or potential agent for intervention with the antimicrobial peptide LL-37 and related disorders