Sanguinarine is an extract of the bloodroot plant Sanguinaria canadensis, a member of the poppy family. It is an inhibitor of protein phosphatases PP1, PP2C and PP2B in vitro. Also inhibits mitogen-activated protein kinase phosphatase-1 (MKP-1) and other enzymes. Sanguinarine exerts a protective effect in cerebral ischemia, and this effect is associated with its anti-inflammatory and anti-apoptotic properties. It was clinically tested as an agent against gingivitis and tooth plaques.

Mertansine (Maytansine) is a 19–member ansa macrolide structure attached to a chlorinated benzenering. It was originally isolated from the shrub Maytenus ovatus. Mertansine (DM1) is a tubulin inhibitor, it inhibits the assembly of microtubules by binding to tubulin, with a linker structure can create an antibody-drug conjugate (ADC). Mertansine is a potent microtubule-targeted compound that induces mitotic arrest and kills tumor cells at sub-nanomolar concentrations. The antimitotic effect of maytansine has been attributed to its ability to inhibit microtubule assembly by binding to tubulin with a KD of ~ 1 umol/L, at or near the vinblastine-binding site. Experimental ADCs with the SPP-DM1 design include lorvotuzumab mertansine. DM1 can also be linked to an antibody using the SMCC (4-(3-mercapto-2,5-dioxo-1-pyrrolidinylmethyl)-cylohexanecarboxylic acid) linker, in which case the International Nonproprietary Name of the conjugate formed contains the word emtansine. DM1 and its attachment via these linkers result from ImmunoGen Inc research. Trastuzumab emtansine (T-DM1) is an anti-HER2/neu antibody-drug conjugate.

GSK1070916 is a novel, azaindole derived, reversible and ATP-competitive inhibitor of the Aurora B/C kinases. GSK1070916 inhibits the proliferation of tumor cells and has antitumor effects in 10 human tumor xenograft models including breast, colon, lung, and two leukemia models. Nemucore Medical Innovations and Cancer Research UK are developing NMI 900 (previously GSK 1070916) for the intravenous treatment of cancer. The product was originally developed by GlaxoSmithKline. A phase I/II trial in patients with solid tumours has been completed in the UK. Phase II development in ovarian cancer is underway in the US.

INCB3284 or INCB-3284 Incyte’s internally developed, oral human CCR2 antagonist for the treatment of chronic inflammations. It is in Phase IIa trial of patients with rheumatoid arthritis (RA).

Levovirin is a guanosine nucleoside analog and the L-enantiomer of ribavirin. It is an investigational drug for the treatment of hepatitis C virus-mediated diseases. Levovirin has a similar immunomodulatory potency to ribavirin in vitro without accumulating in red blood cells or causing hemolytic anemia, a known side effect of ribavirin. Levovirin has been shown to stimulate host immune responses (enhanced Th1 and reduced Th2 cytokine expression). Significantly improved oral absorption of levovirin was achieved following administration of a valine ester prodrug of levovirin R1518. Levovirin was found more potent to inhibit Tick-borne encephalitis virus (TBEV) on the basis of robust binding affinity between protein-drug interactions. This finding may help to understand the nature of helicase and development of specific anti-TBEV therapies.

Acteoside (verbsacoside) is the one of the main active phenylethanoid glycosides from Cistanche deserticola, Lantana camara and some others herbs. It is known to have antioxidant and neuroprotective activity, and herbs containing it are used to enhance memory and can be studied for the treatment of Alzheimer's disease. It is known, that amyloid fibrils accumulation in cerebral can easily lead to neurodegenerative disorders. Acteoside has been reported to inhibit Aβ42 aggregation by activating nuclear translocation of the transcription factor NF-E2-related factor 2 (Nrf2), increasing heme oxygenase-1 (HO-1) expression. It has also been shown that acteoside could decrease nitric oxide synthase (NOS) activity and caspase-3 expression. Acteoside is a natural antioxidant product unlike other anti-tumor compounds, is an inhibitor of protein kinase C (PKC). In addition Reh-acteoside, a general acteoside of Rehmannia leaves was studied in phase 2/3 clinical trials for patients with IgA nephropathy.

Idazoxan is an alpha2 receptor antagonist which also shows activity at imidazoline I1 and I2 receptors and modulates the release of dopamine. Idazoxan was in phase II development in the US. Later the development of idazoxan for schizophrenia was discontinued. It was also in clinical trials for cognition disorders in United Kingdom, and was also discontinued. Idazoxan is used in scientific research as a tool for the study of alpha 2-adrenoceptors. Idazoxan`s diastereoisomers possess different relative selectivity for alpha2- pre- and postsynaptic receptors: (+)-idazoxan was 7-8 times more potent than (-)-idazoxan in inhibiting p-[3H]aminoclonidine binding, and 40 times more active in antagonizing clonidine at presynaptic level, indicating a better selectivity for alpha2-presynaptic sites. The pre- and postsynaptic alpha2-adrenoceptors have a different affinity for the two enantiomers of idazoxan. Although the stereoisomers are closely related structurally, (+)-idazoxan possesses a stronger affinity for presynaptic sites. This stereoselectivity was less evident for postsynaptic sites. In rats and dogs, both enantiomers antagonized the sympathoinhibitory effects of clonidine. In rats, (+)- idazoxan was 4-7 times more potent than (-)- idazoxan and 3-8 times more than (-)- idazoxan in dogs. A same order of potency was observed against the sedative effects of clonidine and azepexole in chicks, (+)- idazoxan being 8 times more potent than (-)- idazoxan. Although (+)- idazoxan was more potent than (-) idazoxan, binding studies revealed (-)- idazoxan to be more selective than (+)- idazoxan at central sites. It is concluded that (+)- idazoxan antagonizes both alpha-1 and alpha-2 adrenoceptors and (-)- idazoxan is selective for alpha-2 adrenoceptors. In the pithed rat, only (-)- idazoxan possesses both alpha-1 and alpha-2 agonistic effects.

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).

RO-20-1724 is a potent inhibitor of Phosphodiesterase 4 (PDE4) originally developed by Roche. It showed some promise as a potential treatment for psoriasis, but it was discontinued when it could not match the efficacy of existing treatments. RO-20-1724 was also investigated as a potential treatment for asthma and septic shock.

Shikonin is a major naphthoquinone compound found in the roots of Lithospermum erythrorhizon and exhibits powerful anticancer activities for various cancer cells. Shikonin and its derivatives are characterized by a wide spectrum of antibacterial activities: high antibacterial activity towards Gram-positive bacteria (Staphylococcus aureus et al.), a stable fungicidal effect towards Candida and Trichosporon fungi. Shikonin normalizes the production of the key mediators of inflammation IL-1 and IL-2, IFN-γ, reduces vascular permeability in the focus of inflammation, exhibiting a marked anti-inflammatory effect. Combined therapy with applications of a bio-polymeric film with shikonin and its esters (naphthoquinone derivatives) led to an obvious improvement of the clinical parameters and reduced the morphological signs of the buccal mucosal lesions. The drug was well tolerated by all patients and no side effects were recorded. Shikonin, as a naturally occurring, low-molecular-weight pan-chemokine receptor inhibitor, constitutes a basis for the development of novel anti-HIV therapeutic agents.