Streptonigrin is an antibiotic produced by Streptomyces flocculus. Streptonigrin exhibits activity as a broad spectrum antibiotic against both Gram-positive and Gram-negative bacteria. Streptonigrin shows antitumor activity against sarcomas, carcinomas, leukemias and lymphomas in vivo and in vitro. Due to its high toxicity, streptonigrin has not recieved widespread clinical use.

Amonafide L-malate (AS1413, Xanafide) is a DNA intercalator and topoisomerase II inhibitor that induces apoptosis by disrupting chromatin organisation independently of ATP. This is different from classical topoisomerase II inhibitors which induce apoptosis by causing extensive DNA damage. Amonafide L-malate is also able to evade P-glycoprotein and related transporters that contribute to multi-drug resistance. AS1413 had orphan drug status in both the U.S. and the E.U. for the treatment of AML and also received Fast Track status from the U.S. FDA for the treatment of secondary AML. Amonafide L-malate was originated by Xanthus Pharmaceuticals. It was added to Antisoma's pipeline through the acquisition of Xanthus Pharmaceuticals, Inc. in June 2008. Antisoma discontinued development of Amonafide L-malate after data from the open-label, international Phase III ACCEDE trial in over 420 patients showed that 600 mg/m 2 IV amonafide for 5 days plus cytarabine missed the primary endpoint of significantly improving initial remission rate, defined as the proportion of patients who achieve CR or CRi, vs. daunorubicin plus cytarabine.

Gaboxadol (or THIP) is a direct GABA mimetic ligand at delta-containing receptors. Gaboxadol went into human clinical trials to test if the drug promoted sleep. It was generally well tolerated. Gaboxadol enhances delta power in NREM sleep in humans. Gaboxadol failed in Phase III for sleep studies. The side effects of Gaboxadol have been described as mild and similar in quality to those of other GABA-mimetics. Gaboxadol is in development with Ovid Therapeutics as a treatment for Angelman syndrome, fragile X syndrome and epilepsy.

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.

Gossypol is a substance that is found in the cotton plant. It is removed from the seeds and used for medicine. Gossypol is effective as a nonhormonal male contraceptive; however, it has been documented to have irreversible effects on male fertility. Gossypol is reported to exhibit antioxidant, anticancer, antivirus, antiparasitic, and antimicrobial properties and lower plasma cholesterol. Nausea, emesis, anorexia, diarrhea, altered taste sensation, small intestine obstruction, and fatigue have been recorded in clinical trials as adverse reactions. Large amounts of gossypol can decrease potassium levels in the body. Low potassium levels can increase the side effects of digoxin.

R406 (TAMATINIB) is an ATP-competitive inhibitor of spleen tyrosine kinase (Syk), which plays a key role in the signaling of activating Fc receptors and the B-cell receptor (BCR). R406 blocked Syk-dependent FcR-mediated activation of monocytes/macrophages and neutrophils and BCR-mediated activation of B lymphocytes. R406 was selective as assessed using a large panel of Syk-independent cell-based assays representing both specific and general signaling pathways. Consistent with Syk inhibition, oral administration of R406 to mice reduced immune complex-mediated inflammation in a reverse-passive Arthus reaction and two antibody-induced arthritis models. R406 is the active compound of pro-drug Fostamatinib (R-788). Fostamatinib is being developed by Rigel Pharmaceuticals for the treatment of immune thrombocytopenic purpura (ITP) and IgA nephropathy.

4-Amino-N-(3-chloro-4-fluorophenyl)-N'-hydroxy-1,2,5-oxadiazole-3-carboximidamide (Epacadostat) is an orally available hydroxyamidine and inhibitor of indoleamine 2,3-dioxygenase (IDO1), with potential immunomodulating and antineoplastic activities. epacadostat targets and binds to IDO1, an enzyme responsible for the oxidation of tryptophan into kynurenine. By inhibiting IDO1 and decreasing kynurenine in tumor cells, epacadostat increases and restores the proliferation and activation of various immune cells, including dendritic cells (DCs), NK cells, and T-lymphocytes, as well as interferon (IFN) production, and a reduction in tumor-associated regulatory T cells (Tregs). Activation of the immune system, which is suppressed in many cancers, may inhibit the growth of IDO1-expressing tumor cells. IDO1 is overexpressed by a variety of tumor cell types and DCs. Epacadostat is in clinical development as a novel orally active immuno-oncological therapy.

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. ( )- idazoxan is equipotent for antagonizing postsynaptic alpha-I and alpha-2 adrenoceptors. It is also a potent alpha-2 antagonist at presynaptic and central sites and is 4-8 times more potent than (-)- idazoxan but less selective.

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.