Basimglurant is a potent, selective, and safe mGlu5 inhibitor with good oral bioavailability and long half-life supportive of once-daily administration, good brain penetration, and high in vivo potency. It has antidepressant properties that are corroborated by its functional magnetic imaging profile as well as anxiolytic-like and antinociceptive features. In electroencephalography recordings, basimglurant shows wake-promoting effects followed by increased delta power during subsequent non-rapid eye movement sleep. Basimglurant has favorable drug-like properties, a differentiated molecular mechanism of action, and antidepressant-like features that suggest the possibility of also addressing important comorbidities of MDD including anxiety and pain as well as daytime sleepiness and apathy or lethargy. Basimglurant is being under development by Roche for the treatment of treatment-resistant depression (as an adjunct). It is in phase II clinical trials for this indication.

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.

Acolbifene, the active metabolite of EM-800, was identified as a pure antagonist that acts on both activation domains of the ERs. It is in Phase III clinical trials for the prevention of breast cancer and vasomotor symptoms (Hot flush) in postmenopausal women. Most commonly reported adverse events included irregular menses, leg/muscle cramps, diarrhea, and hot flashes. No serious adverse events were reported.

R-etodolac (SDX-101) is the non-cyclooxygenase 2-inhibiting R-enantiomer of the non-steroid anti-inflammatory drug etodolac (1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid). The absolute configuration of the enantiomer is R-(-)-etodolac. R-etodolac specifically bound retinoid X receptor (RXRalpha), inhibited RXRalpha transcriptional activity, and induced its degradation by a ubiquitin and proteasome-dependent pathway. In addition R-etodolac can disrupt the beta-catenin signaling pathway. R-etodolac exerts antineoplastic properties. R-etodolac was in phase 2 studies for the treatment of hematologic malignancies however development was discontinued.

GV 150526A (gavestinel) is an investigational drug for a neuroprotective therapy of acute ischemic stroke within 6 hours of symptom onset. It is a potent and selective non-competitive antagonist at the glycine site of the N-methyl-D-aspartate receptor (NMDA) which reduces infarct volume in experimental stroke models. Gavestinel acts at the strychnine-insensitive glycine binding site of the NMDA receptor-channel complex with nanomolar affinity (pKi = 8.5), coupled with high glutamate receptor selectivity. Gavestinel displays higher than 1000-fold selectivity over NMDA, AMPA and kainate binding sites and is orally bioavailable and active in vivo. GV 150526A inhibited convulsions induced by NMDA in mice, when administered by both IV and po routes (ED50 = 0.06 and 6 mg/kg, respectively). The safety and efficacy of GV150526 were studied in two phase III randomized placebo-controlled clinical trials of acute ischemic stroke patients within 6 h from onset [The Glycine Antagonist in Neuroprotection (GAIN) International and GAIN Americas Trials] sponsored by GlaxoSmithKline. The results of these trials suggested that gavestinel was not of substantial benefit or harm to patients with primary intracerebral hemorrhage.

Hyodeoxycholic acid, also known as HDCA, is a secondary bile acid. Natural 6alpha-hydroxylated bile acids are receptor-specific activators of nuclear liver X receptor alpha (LXRalpha), a nuclear receptor regulating the expression of the cholesterol 7alpha-hydroxylase gene. AHRO-001 (Hyodeoxycholic acid) is in phase I clinical trials for the treatment of atherosclerosis. Through a complex signaling processes utilizing LXR receptors, the compound is designed to increase the efficiency of cholesterol efflux using the HDL cells, which act on all cholesterol in the arterial circulation as well as in the lipid core of plaque deposits in the artery walls. Use of AHRO-001 has shown no adverse effects on morbidity, mortality or toxicity and has been well tolerated at high doses.

18alpha-Glycyrrhetinic acid (18-GA), a derivative of enoxolone, is used to inhibit gap junctions and furthermore, it has anti-proliferative properties against various cancer types by affecting the cell cycle proteins. 18alpha-Glycyrrhetinic acid, is a non-selective inhibitor of 11beta-hydroxysteroid dehydrogenases isozymes and results in increased whole body insulin sensitivity and decreased glucose production.

Cucurbitacin I (JSI-124) is a novel selective triterpenoid that acts as a potent inhibitor of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway with anti-proliferative and anti-tumor properties. Cucurbitacin I specifically suppresses levels of tyrosine phosphorylated STAT3 in v-Src-transformed NIH 3T3 cells and in A549 cells (IC50 = 500 nM) resulting in inhibition of STAT3 DNA binding and reduced STAT3-mediated gene transcription. It also suppresses JAK2 phosphorylation but does not affect Src, ERK, JNK or Akt. In nude mice, cucurbitacin I (1 mg/kg/day) suppressed the growth of various tumors expressing constitutively active STAT3.1 It promotes the differentiation of dendritic cells and macrophages and enhances the effect of cancer immunotherapy. Cucurbitacin I (1 µM for 2 hours) reduced clonogenicity of nasopharyngeal carcinoma cells in vitro and suppresses tumor growth in mice (1.3 mg/kg).

11-NOR-9-CARBOXY-DELTA9-TETRAHYDROCANNABINOL (THC-COOH) is the main the non-psychoactive metabolite of Delta9-Tetrahydrocannabinol. Being most abundant in bodily fluids, it has become an established marker of cannabis consumption in forensic, clinical and environmental analyses. Among the cannabinoids tested as potential inhibitors of the drug efflux transporter P-glycoprotein (Pgp), which is responsible for the multidrug-resistance of a tumour and normal cells, THC-COOH behaved as a substrate and was the most active in stimulating Pgp-dependent ATPase. It displayed analgesic and anti-inflammatory properties apparently by inhibiting cyclooxygenase and 5-lipoxygenase activities. THC-COOH was not an anxiolytic or anxiogenic drug but abolished the anxiogenic behavioral effect of Delta9-Tetrahydrocannabinol.

Eugenol is sometimes called clove oil because it is the active element in cloves. It causes the aromatic smell typical of cloves and because of this property is often found in perfumes. Eugenol’s properties make it a good local antiseptic and analgesic. It is used in dentist offices to make zinc-oxide eugenol paste for temporary fillings. Eugenol also demonstrates antifungal and antimicrobial activity, showing efficacy against Candida albicans biofilms, Listeria monocytogenes and Escherichia coli. Eugenol is further described to induce reactive oxygen species (ROS) production and to scavenge ROS, thus demonstrating prooxidant and antioxidant effects. Also, Eugenol is used as a pesticide.