Omaveloxolone (RTA-408) is a synthetic triterpenoid exerting antioxidant inflammation modulator properties. It activates the transcription factor Nrf2 and inhibits NF-κB signaling. Omaveloxolone demonstrated antioxidant, anti-inflammatory, and anticancer activities. Reata Pharmaceuticals is developing omaveloxolone for the treatment of cancers, Friedreich's ataxia and mitochondrial disorders.

VBP-15 FREE ALCOHOL, also known as Vamorolone and VBP-15, is an anti-inflammatory compound used in the treatment of muscular dystrophy. Vamorolone is a dissociative steroid that retains high affinity binding and nuclear translocation of both glucocorticoid (agonist) and mineralocorticoid (antagonist) receptors, but does not show pharmacodynamic safety concerns of existing glucocorticoid drugs at up to 20 mg/kg/day. Vamorolone is a first-in-class steroidal multi-functional drug that shows potent inhibition of pro-inflammatory NFkB pathways via high-affinity binding to the glucocorticoid receptor, high affinity antagonism for the mineralocorticoid receptor, and membrane stabilization properties. Pre-clinical data in multiple mouse models of inflammation showed retention of anti-inflammatory efficacy, but loss of most or all side effects. Vamorolone has received Orphan Drug Designation in the US and Europe and is being developed for chronic treatment of boys with Duchenne Muscular Dystrophy (DMD).

Juvantia Pharma and Orion developed ORM-12741, also known as ORM-10921, a novel selective antagonist of alpha-2C adrenoceptors for the treatment of depression and Alzheimer's disease. ORM-12741 participated in phase II clinical trial where was evaluated the safety and efficacy of the drug in patients with Alzheimer's disease. In spite of the successfully completed phase II, further study of the drug for this disease was discontinued. In addition, ORM-12741 participated in clinical trial phase II to prove the concept that this drug could prevent blood vessel spasms for Raynaud's phenomenon. Raynaud's phenomenon is a disorder of the digital blood vessels resulting in episodic impairment of blood flow. However, this study was terminated because of the recommendation by study Data and Safety Monitoring Committee to the sponsor following the interim analysis of 8 subjects.

Andrographolide, a diterpenoid, is known for its anti-inflammatory effects. It can be isolated from various plants of the genus Andrographis, commonly known as 'creat'. Andrographolide has been tested for its anti-inflammatory effects in various stressful conditions, such as ischemia, pyrogenesis, arthritis, hepatic or neural toxicity, carcinoma, and oxidative stress. Apart from its anti-inflammatory effects, andrographolide also exhibits immunomodulatory effects by effectively enhancing cytotoxic T cells, natural killer (NK) cells, phagocytosis, and antibody-dependent cell-mediated cytotoxicity (ADCC). The properties of andrographolide, such as its ability to induce apoptosis of cancer cells and inhibition of DTH, its anti-oxidative and cytoprotective effect, and its ability to enhance CTLs and NK cell activation makes it a potent antiviral agent. Andrographolide inhibited the growth of human breast, prostate, and hepatoma tumors. Andrographolide could be a potent anticancer agent when used in combination with other chemotherapeutic agents.

Dexanabinol is the synthetic cannabinoid. It is inactive as a cannabimimetic, but exhibits pharmacological properties characteristic of an N-methyl-D-aspartate (NMDA)-receptor antagonist. It blocks NMDA-receptors stereospecifically by interacting with a site close to, but distinct from, that of uncompetitive NMDA-receptor antagonists and from the recognition sites of glutamate, glycine, and polyamines. This agent also scavenges peroxy radicals and protects neurons from the damages of reactive oxygen species. Furthermore, dexanabinol inhibits the activity of nuclear factor kappa B (NF-kB), thereby preventing the expression of NF-kB target genes, such as tumor necrosis factor alpha, cytokines and inducible nitric oxide synthase. Dexanabinol is a potent cerebroprotective agent, with a therapeutic window of about 4 h. Dexanabinol is safe, but is not efficacious in the treatment of traumatic brain injury. It was introduced into clinical trials for breast cancer and advanced solid tumors.

Methysticin is a kavalactone originally found in Piper methysticum (kava plant). Methysticin exhibits neuroprotective, neuromodulatory, and antifungal activities. Methysticin may also display anti-inflammatory benefit, inhibiting activation of NF-κB in lung adenocarcinoma tissue. Methysticin activates Nrf2 in neurons and astroglia, protecting against amyloid-β (Aβ)-induced neurotoxicity. This compound displays antimicrobial efficacy against species of Fusarium, Trichoderma, and Colletotrichum. Additionally, methysticin inhibits peak amplitude of voltage-gated Na+ channels in hippocampal neurons. Methysticin administration activates the Nrf2 pathway and reduces neuroinflammation, hippocampal oxidative damage and memory loss in a mouse model of AD. Therefore, kavalactones might be suitable candidates to serve as lead compounds for the development of a new class of neuroprotective drugs.

(s)-Thalidomide is an enantiomer of immunomodulatory agent Thalidomide. Thalidomide enantiomers are converted to each other in vivo, and Thalidomide contains both left and right-handed isomers in equal amounts. (s)-Thalidomide has proven efficacy in multiple myeloma. s-thalidomide-induced apoptosis associated with increases in I-kB activity, downregulation of NF-kB activity and an increase in Bax: Bcl-2 ratio. In cells cultured with s-thalidomide, there was a four-fold downregulation of the NFkB gene that was associated with a significant decrease in its protein activity.