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).

Balaglitazone, also known as DRF-2593; NNC-61-0645; NNC-61-2344; NN-2344; NNC-610645; NNC-612344, is an agonist of peroxisome proliferator-activated receptor (PPAR)γ. Balaglitazone plays an important role in the regulation of insulin, triglycerides and lipid metabolism. It is an attractive target for the therapy of Type II Diabetes. Balaglitazone is a partial agonist of PPARγ. It has showed potent effects on lowering blood glucose in various animal models. Balaglitazone passed phase III clinical trial for the treatment of type 2 diabetes. However, Dr. Reddy's Laboratories decided to terminate further clinical development of balaglitazone. Balaglitazone exists as two enantiomers: BALAGLITAZONE, (S)- and BALAGLITAZONE, (R)-. A capillary electrophoresis method for separation of a racemic mixture of glitazone compounds has being used. The method separated the R and S enantiomers of balaglitazone, and showed that the samples contained an equal (50:50) quantity of the enantiomers as a mixture. The Rs for the separations were 3.5 for balaglitazone enantiomers.

Balaglitazone, also known as DRF-2593; NNC-61-0645; NNC-61-2344; NN-2344; NNC-610645; NNC-612344, is an agonist of peroxisome proliferator-activated receptor (PPAR)γ. Balaglitazone plays an important role in the regulation of insulin, triglycerides and lipid metabolism. It is an attractive target for the therapy of Type II Diabetes. Balaglitazone is a partial agonist of PPARγ. It has showed potent effects on lowering blood glucose in various animal models. Balaglitazone passed phase III clinical trial for the treatment of type 2 diabetes. However, Dr. Reddy's Laboratories decided to terminate further clinical development of balaglitazone. Balaglitazone exists as two enantiomers: BALAGLITAZONE, (S)- and BALAGLITAZONE, (R)-. A capillary electrophoresis method for separation of a racemic mixture of glitazone compounds has being used. The method separated the R and S enantiomers of balaglitazone, and showed that the samples contained an equal (50:50) quantity of the enantiomers as a mixture. The Rs for the separations were 3.5 for balaglitazone enantiomers.

Olesoxime (TRO19622) a small-molecule with a cholesterol-like structure has remarkable neuroprotective properties for motor neurons in cell culture and in rodents. The biopharmaceutical company Trophos initially developed this compound. This medicine is in phase II clinical trial in treating spinal muscular atrophy and in phase I for patients with stable relapsing remitting multiple sclerosis. This drug was also investigated in phase III clinical trial for amyotrophic lateral sclerosis, but it did not demonstrate a significant increase in survival versus placebo and that study was discontinued. Preclinical studies have demonstrated that the olesoxime promoted the function and survival of neurons and other cell types under disease-relevant stress conditions through interactions with the mitochondrial permeability transition pore (mPTP).

1,9-Dideoxyforskolin (DFK) is an inhibitor of glucose transporter, has been synthesized in 8 steps and 37% overall yield. 1,9-Dideoxyforskolin is a biologically inactive forskolin analog and does not stimulate adenylyl cyclase. DFK mimics some activity of forskolin, demonstrating alteration of K+ channel activity, reversal of doxorubicin resistance in multidrug resistant sarcoma cells, protection against TNF-α-mediated cytotoxicity, and desensitization at GABAA receptors. The inhibitory effect of DFK on high K (+)-induced contraction was antagonized by an increase in extracellular Ca2+ concentration. DFK inhibited the increase in cytosolic Ca2+ level and contraction in parallel whereas forskolin inhibited the contraction more strongly than the cytosolic Ca2+ level. These results suggest that DFK, but not forskolin, inhibits vascular smooth muscle contraction by a Ca2+ channel blocker-like action.

Echinacoside is a caffeic acid glycoside which is constituted from a trisaccharide consisting of two glucose and one rhamnose moieties glycosidically linked to one caffeic acid and on hydroxytyrosol residue at the centrally situated rhamnose. Echinacoside is the basic component of the roots of E. angustifolia and E. pallida, ranging from 0.5 to 1.0%. Echinacoside is reported to possess the immunostimulatory and high antioxidant activities

Maslinic acid is a pentacyclic triterpene occur naturally in many herbs and plant foods. It is found in the protective wax-like coating of the leaves and fruit of Olea europaea and is one of the ingredients in olive oil. Benefits of the olive oil triterpenes (oleanolic and maslinic acid) on the primary prevention of cardiovascular disease in addition to their bioavailability and disposition have been investigated in Phase 3 clinical trial in healthy participants. Maslinic acid is used in skin care products and dietary supplements. Maslinic acid exerts a wide range of biological activities including antitumor, antidiabetic, anti-obesity, antioxidant, anti-inflammatory, cardioprotective, neuroprotective and antimicrobial. In vitro anti-diabetic effects of maslinic acid are exhibited by increasing glycogen content and inhibiting glycogen phosphorylase activity in HepG2 cells. It was shown to induce the phosphorylation level of IRβ-subunit, Akt, and GSK3β with specific activation of Akt. In vivo maslinic acid treatment of mice fed with a high-fat diet reduced the model-associated adiposity and insulin resistance, and increased the accumulated hepatic glycogen content. In hyperglycemia mice, the elevation of blood glucose level caused by adrenaline or glucose was antagonized by maslinic acid significantly. Diabetic rats pretreated with high-dose maslinic acid had lower blood glucose levels, reduced infarct volumes and improved neurological scores. Less glutamate overflow was also observed in maslinic acid -treated rats after 2 hours of ischemia followed by 24 and 72 hours of reperfusion. In addition, maslinic acid treatment enhanced the glial glutamate transporter GLT-1 expression at the protein and mRNA levels. Direct beneficial effect in cerebral ischemic injury in rats may be correlated with the promotion of glutamate clearance by NF-κB-mediated GLT-1 up-regulation. Through NF-kappa B and MAPK/AP-1 signaling pathways maslinic acid suppresses RANKL-induced osteoclastogenesis as well.

Selfotel is a competitive NMDA antagonist with (-)-enantiomer is more active than ( )-enantiomer. Selfotel was investigated in phase III clinical trials for ischemic stroke and severe head injury. Development of the drug was discontinued due to lack of efficacy and possible neurotoxicity discovered in clinical trials.

The mixture of artemotil and alpha-arteether is used in patients with cerebral malaria. Both beta and alpha/beta arteether have comparable activity and are curative at a dose of 5 mg/kg for 3 days against blood-induced Plasmodium cynomolgi B infection in the rhesus monkey; alpha arteether alone is slightly less active, with a 50% cure rate at the above dose. Alpha-arteether is a fourth generation anti-bacterial and anti-fungal drug. Alpha-arteether was found to inhibit the growth of E-coli strains defective in DNA-gyrase enzyme. DNA gyrase mutants were sensitive to α-arteether whereas the wild type of E-coli having intact DNA gyrase genes were not sensitive to α-arteethers. In fact, the isomer of this compound, β-arteether, does not exhibit this activity. The beta-isomer of arteether was characterized by a longer elimination half-life and a relatively larger volume of distribution than the alpha-isomer, suggesting that beta-arteether may be responsible for the prolonged in vivo schizontocidal activity.

Pseudohypericin is a predominant naphthodianthrone from St. John’s wort (Hypericum perforatum L.) phytomedicinal drug. It has been shown to specifically inhibit protein kinase C and dopamine-β-hydroxylase. Also, pseudohypericin induces apoptosis and selectively antagonizes corticotropin-releasing factor in murine models. Inhibition of thioredoxin system by pseudohypericin showed appreciable anticancer properties of this natural compound. Pseudohypericin has antiretroviral activity, it has potential therapeutic value in diseases such as AIDS. Pseudohypericin is implicated in the antidepressant efficacy of St. John's wort.