SGI-1776 is a PIM-kinase inhibitor, developed by SuperGen Inc. SGI-1176 was tested in clinical trials against relapsed/refractory leukemias, prostate cancer and Non Hodgkin's Lymphoma, but the dose limiting toxicity of cardiac QTc prolongation was identified and clinical development of SGI-1776 was terminated.

JNJ-26854165 (Serdemetan), a novel tryptamine derivative, was developed as an activator of p53, and its initially proposed mechanism of action involved preventing the association of HDM2 with the proteasome and thereby stabilizing HDM2 substrates such as p53. Consistent with this proposed mechanism, Serdemetan induced apoptosis in acute myeloid and lymphoid leukemia cell lines and in primary acute leukemia isolates. Serdemetan is currently being evaluated in Phase I clinical trials in patients with non-small cell lung cancer; prostate cancer; solid tumours.

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.

Japan Tobacco developed JTV-519 (known also as K201) as an antiarrhythmic agent. This drug was in Phase II trials for the potential treatment of Atrial Fibrillation, but study was terminated. In experimental myofibrillar overcontraction models, JTV-519 demonstrated greater cardioprotectant effects than propranolol, also, this drug investigated against heart failure, but then these researches have been discontinued. In addition, K201 was in phase II clinical trial for investigation its topical implementation for Atopic Dermatitis. The mechanism of its action is both complex and controversial, known that it is a non-specific blocker of sodium, potassium and calcium channels (multiple-channel blocker). It is believed to stabilize the closed state of the RyR2 (cardiac ryanodine receptor) by increasing its affinity for the FKBP12.6 (12.6 kDa FK506 binding protein), in addition was suggested, that suppression of spontaneous Ca2 release and the activity of RyR2 contributes, at least in part, to the anti-arrhythmic properties of K201.

Fluperlapine is dibenzazepine chemically and pharmacologically similar to clozapine. Fluperlapine had no cataleptogenic effect and did not inhibit the apomorphine- and d-amphetamine-induced stereotypes. Fluperlapine is fairly effective neuroleptic drug with a fast-acting antipsychotic affect. The effects in movement disorders imply that fluperlapine is less liable than traditional neuroleptics to induce acute extrapyramidal side effects and tardive dyskinesia and is particularly beneficial in the treatment of patients vulnerable to neurological side-effects. It was demonstrated efficacy in the treatment of a variety of medical conditions including schizophrenia, psychosis associated with Parkinson's disease and dystonia. It has the capacity for producing life-threatening agranulocytosis.

Perzinfotel (EAA-090) is a novel squaric acid amide derivative that has been identified as a potential treatment for ischemic brain damage resulting from stroke. EAA-090 is a competitive inhibitor at the NMDA-selective subtype of the glutamate receptor. The compound demonstrates potent inhibitory activity in both in vitro and in vivo models of NMDA-induced excitotoxicity and provides neuroprotective efficacy in several animal models of stroke. EAA-090 is unique among competitive NMDA antagonists in displaying a clear separation between predicted efficacious dose and doses that induce PCP-like psychotomimetic side effects in both animals and humans. This unique profile makes EAA-090 an exciting candidate for assessing the neuroprotective potential of the competitive NMDA mechanism.

AstraZeneca was developing AZD-7762 for the treatment of solid tumours. AZD-7762 is a potent inhibitor of Chk1 that binds in the ATP binding pocket (IC50 of 5nM; Ki of 3.6nM). AZD-7762 has activity on a range of other kinases {examples with a < 5 fold selectivity included Rous sarcoma oncogene cellular homolog (SRC) family members (e.g., Fgr, Fyn, lymphocyte-specific protein-tyrosine kinase [Lck], and Lyn, but not SRC), Flt1/3, colony stimulating factor receptor (CSF1R), RET, Abelson tyrosine kinase (Abl), and checkpoint kinase 2 (Chk2)}. It is not known if these in vitro kinase inhibitions translate into an effect in vivo. In combination with DNA-damaging agents (gemcitabine, topotecan, doxorubicin, and cisplatin), AZD-7762 inhibits tumour cell growth in vitro with a mode of action that correlates with Chk1 inhibition and abrogation of the Gap 2 (G2) and S phase checkpoints. Rightward shifts in 50% growth inhibition (GI50) values over DNA-damaging agents alone ranged from 5- to 20-fold with gemcitabine demonstrating the largest shifts followed by topotecan. In combination with radiation, AZD-7762 enhances tumour cell growth inhibition and death with survival enhancement ratios ranging from 1.7 to 1.9. Triple combinations with AZD-7762, gemcitabine, and radiation yield the largest survival enhancement ratios. AZD-7762 had been in phase I clinical trials by AstraZeneca for the treatment of solid tumors. However, this study was terminated for the safety reason in 2011.

Norletimol is a Schiff base with promising anti-inflammatory properties. The time taken for elimination of 50% of the Norletimol dose in the urine was approximately five hours. As an antirheumatic agent it was tested in clinical trials in Iraq. It was used in progressive myopia in children.

Bardoxolone methyl, the C-28 methyl ester of 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO) known as CDDO-Me or RTA 402, is one of the derivatives of synthetic triterpenoids. Bardoxolone methyl directly blocks IKKbeta activity and thereby the NF-kappaB pathway by interacting with Cys-179 in the IKKbeta activation loop. Binding of bardoxolone methyl to Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1 (Keap1) disrupts its critical cysteine residues, leading to the release of the nuclear factor erythroid 2-related factor 2 (Nrf2), which hinders its ubiquitination and finally leads to its stabilization and nuclear translocation. In the nucleus, Nrf2 activates the transcription of phase 2 response genes, leading to a coordinated antioxidant and anti-inflammatory response. In addition, it acts as an antagonist of the peroxisome proliferator-activated receptor gamma. Through Keap1/Nrf2 and nuclear factor-κB pathways, this agent can modulate the activities of a number of important proteins that regulate inflammation, redox balance, cell proliferation and programmed cell death. This agent is generally well tolerated, but it may increase adverse cardiovascular events. Presently, it is being further tested for the treatment of patients with chronic kidney disease, cancer, and pulmonary arterial hypertension.