Salvinorin A has been reported to be the most potent naturally occurring hallucinogen, with an effective dose in humans in the 200- to the 1,000-μg range when smoked; it has been reported to induce an intense hallucinatory experience in humans, with a typical duration of action being several minutes to an hour or so. Salvinorin A is a highly selective agonist of the kappa-opioid receptor (KOR) with few off-target effects. It is a potent and selective dilator of the cerebral vasculature, exhibits rapid penetration through the blood-brain barrier, has potent anti-inflammatory properties, and has the ability to preserve neurovascular unit integrity. As such, salvinorin A is an ideal compound for the prevention and treatment of cerebral vasospasm following subarachnoid hemorrhage.

Licochalcone A (LicA) is a flavonoid isolated from the famous Chinese medicinal herb Glycyrrhiza uralensis Fisch and has a wide spectrum of pharmacological activities such as anti-oxidant, anti-bacterial, anti-viral, and anti-cancer. However, its pharmacological mechanism is not well defined. The anti-Inflammatory effects of LicA on IL-1β-Stimulated human osteoarthritis chondrocytes was reached by activating Nrf2 signaling pathway. LicA showed anti-proliferative and apoptotic effects in breast cancer cells through regulating Sp1 and apoptosis-related proteins in a dose- and a time-dependent manner. In addition, the chemotherapeutic potential of LicA for treatment of human cervical cancer was achieved by inhibition of PI3K/Akt/mTOR signaling.

Trichostatin A (TSA) was originally isolated as an antifungal antibiotic along with its fermentation congeners trichostatin B ((TSA)3-Fe) and the D-glucopyranosides trichostatin C and D. TSA inhibits HDAC in the low nanomolar range and is an inducer of histone hyperacetylation, both in vitro and in vivo. It inhibits all class I and II deacetylases to a similar extent in both tumor and non-tumor cells, although HDAC4 is slightly resistant when compared with HDAC1 and HDAC6. Class III HDAC is not affected by TSA. It has been shown that TSA dosedependently inhibits growth and induces apoptosis in a plethora of carcinoma cell lines in vitro. Recently, it was also found that TSA inhibits angiogenesis, which is important for the growth and metastasis of solid tumors, both in vivo and in vitro. In HT-29 colon carcinoma cells, a single dose of TSA induced transient hyperacetylation of histone H4 resulting in the induction of p21WAF1/Cip1 and inhibition of cellular proliferation at both the G1 and G2 phases of the cell cycle. Growth inhibition was associated with decreased cyclin D1 mRNA and cdk6 protein levels and increased cyclin D3 protein and p21WAF1/Cip1 mRNA levels. Cyclin D1 protein, cyclin D3 mRNA, cdk2 and cdk4 remained unaffected. In addition, TSA induced apoptosis by upregulating the expression of the pro-apoptotic genes ID1, ID2 and ID3, whereas the expression of the anti-apoptotic genes BclxL and Hsp27 was decreased In vivo, TSA induces differentiation and shows chemotherapeutic activity against N-methylnitrosureainduced rat mammary cancer without toxic side effects. TSA may also have therapeutic potential for the treatment of a variety of genetic and infectious diseases since silenced, transduced genes are reactivated probably due to structural changes of the chromatin on integrated viral sequences.

Oxi0-4503 (now known as combretastatin A1 phosphate), a diphosphate prodrug of combretastatin A1, was developed by Mateon therapeutics as a second-generation, dual-mechanism vascular disrupting agent from the combretastatin family. On November 21, 2012, Oxi-4503 has been granted orphan designation by the US Food and Drug Administration for the treatment of acute myelogenous leukemia. It is known that the orphan drug designation qualifies a company for several benefits, including the potential for market exclusivity, development grants, and tax credits. Oxi0-4503 is currently participating in phase I/II clinical trial the treatment of patients with acute myelogenous leukemia or myelodysplastic syndrome. In addition, phase I clinical trial was successfully completed where was studied the safety of Oxi0-4503 in patients with advanced solid tumors.

Latrunculin A is a naturally occurring toxin that can be purified from the red sea sponge Latrunculia magnifica. It disrupts actin polymerization and prevents mitotic spindle formation; therefore preventing proper cellular replication. It was discovered that latrunculin A has strong anticancer effects, and it was investigated as a treatment candidate for peritoneal dissemination of gastric cancer.

Bisphenol A is a small estrogenic monomer that is polymerized to produce polycarbonate plastic and resins used to line metal cans. It is also used to make some dental sealants. Bisphenol A had been considered to be a very weak environmental estrogen. It is able to interact with human estrogen receptors. In addition, it binds strongly to the estrogen-related receptor gamma. Bisphenol A inhibited androgen-induced androgen receptor transcriptional activity. Prenatal exposure to maternal Bisphenol A concentrations were related to higher levels of anxiety, depression, aggression, and hyperactivity in children. Bisphenol A exposure in childhood was associated with higher levels of anxiety, depression, hyperactivity, inattention, and conduct problems. It never found use as a drug.

9-(N-methyl-L-isoleucine)-cyclosporin A (NIM-811, SDZ 811) is a cyclosporin A analog that is completely devoid of immunosuppressive capacity but exhibits potent and selective anti-human immunodeficiency virus type 1 (HIV-1) activity. NIM-811 interferes at two stages of the viral replication cycle: (i) translocation of the preintegration complex to the nucleus and (ii) production of infectious virus particles. NIM-811 induces a concentration-dependent reduction of HCV RNA in the replicon cells with an IC50 of 0.66 uM at 48 h. NIM-811 blocks the mitochondrial permeability transition induced by calcium and inorganic phosphate. NIM-811 blocks cell killing and prevents in situ mitochondrial inner membrane permeabilization and depolarization during tumor necrosis factor-α–induced apoptosis to cultured rat hepatocytes.Novartis discontinued development of SDZ 811 as an oral therapy for hepatitis C and HIV-1 infections.