Otenzepad is the first competitive muscarinic M2 antagonist that is cardioselective and had been in phase III clinical trials for the treatment of arrhythmias and bradycardia. Otenzepad was originally developed by Boehringer Ingelheim Pharma KG (Boehringer Ingelheim) in Germany. The parent company is developing oral and IV formulations of the drug for use in symptomatic bradycardia, sinus bradycardia, sick sinus syndrome and symptomatic arrhythmias after intoxication. However, all these research has been discontinued. Otenzepad binds to muscarinic cholinergic receptors in a simple competitive manner. Its affinity for cardiac (M2) muscarinic receptors is about 7 times greater than for ganglionic (M1) receptors and about 36 times greater than for glandular (M3) receptors. The (+)-enantiomer of otenzepad is about 8 times more potent at M2-receptors than the (−)-enantiomer. In a double-blind study, 48 healthy male volunteers were randomised to single oral doses of placebo or otenzepad (120, 240 or 480mg). Heart-rate (HR) was significantly increased by the 250 and 480mg doses (by 15 and 21 beats/minute, respectively). The 480mg dose also increased Diastolic Blood Pressure (DBP) significantly compared with placebo. The oral pharmacokinetics of otenzepad were investigated in a double-blind study in which 48 healthy male volunteers were randomised to single oral doses of placebo or otenzepad (120, 240 or 480mg). Otenzepad bioavailability was 45%, mean residence time (MRT) was 12.5 hours and tmax occurred 2.5 hours postdose.

Sitravatinib (MGCD516) is a receptor tyrosine kinases (RTK) inhibitor that blocks a wide array of RTKs known to be amplified/overexpressed in sarcomas, which are key regulators of signaling pathways that lead to cell growth, survival and tumor progression. It is involved in driving sarcoma cell growth with IC50 of 3980 nM and is superior to other multi-kinase inhibitors in inhibiting cell proliferation, RTK phosphorylation, and phosphorylation of downstream effectors. The efficacy of sitravatinib was tested using a wide panel of sarcoma cell lines, including malignant peripheral nerve sheath tumor (MPNST), Ewing sarcoma (A673), osteosarcoma (Saos2), and liposarcoma (DDLS, LS141). Both in vitro and in vivo efficacy sitravatinib was significantly better that the other two multi-kinase inhibitors, imatinib and crizotinib. Sitravatinib treatment not only inhibits tumor cell proliferation at low nanomolar concentrations in vitro but also results significant tumor growth suppression in vivo in mouse xenograft models. Sitravatinib is being evaluated in a Phase 1b dose expansion cohort in selected patients with specific genetic alterations that are drivers of tumor growth, with an initial focus on Non-Small-Cell Lung carcinoma (NSCLC) and in other solid tumors where sitravatinib may confer a benefit. Its efficacy and safety is also being tested in Phase II clinical trials in patients with advanced liposarcoma as a monotherapy and NSCLC in combination with nivolumab.

Corticosterone is an adrenocortical steroid, the major glucocorticoid that has modest but significant activities as a mineralocorticoid and a glucocorticoid. Corticosterone is of minor importance in humans but is known, that it has a profound effect on the structure and function of the hippocampus. Brain corticosterone may involve memory storage and emotional stress might cause increases in plasma corticosterone.

18-Methoxycoronaridine (18-MC) is a derivative of ibogaine invented in 1996 by the research team around the pharmacologist Stanley D. Glick from the Albany Medical College and the chemist Martin E. Kuehne from the University of Vermont. In animal studies it has proved to be effective at reducing self-administration of morphine, cocaine, methamphetamine, nicotine and sucrose. 18-MC is a α3β4 nicotinic antagonist and, in contrast to ibogaine, has no affinity at the α4β2 subtype nor at NMDA-channels nor at the serotonin transporter, and has significantly reduced affinity for sodium channels and for the σ receptor, but retains modest affinity for μ-opioid receptors where it acts as an antagonist, and κ-opioid receptors. The sites of action in the brain include the medial habenula, interpeduncular nucleus, dorsolateral tegmentum and basolateral amygdala. Unlike ibogaine and its principal metabolite noribogaine, 18-MC does not increase expression of glial cell line-derived neurotrophic factor (GDNF) in a dopaminergic–like cell line. 18-Methoxycoronaridine is a potent leishmanicide effect against Leishmania amazonensis, a causative agent of cutaneous and diffuse cutaneous leishmaniasis in the New World.

Sepetoprost (also known as ONO-9054), prostaglandin analog was developed as a dual agonist of prostaglandin E3 (EP3) and prostaglandin F (FP) receptors. It is known, that the use of a dual prostaglandin EP3 and prostaglandin F receptor agonists is a novel approach for the reduction of intraocular pressure (IOP) in open-angle glaucoma and ocular hypertension. Sepetoprost was successfully studied in clinical trials phase II for the treatment of open-angle glaucoma, ocular hypertension, and mild open angle-glaucoma.

JNJ-42396302 was under investigation in clinical trial NCT01732237 (A Study to Investigate the Pharmacokinetics of JNJ-42396302, JNJ-53773187, and JNJ-42692507 in Healthy Male Participants).

Camptothecin-20(S)-O-propionate (CZ48) is a prodrug of camptothecin, an alkaloid isolated from the Chinese tree Camptotheca acuminata, with potential antineoplastic activity. Upon entry into cells, camptothecin-20(S)-O-propionate is hydrolyzed by esterases into the active form camptothecin. Camptothecin selectively stabilizes topoisomerase I-DNA covalent complexes, thereby inhibiting religation of topoisomerase I-mediated single-strand DNA breaks and producing potentially lethal double-strand DNA breaks when encountered by the DNA replication machinery. CZ48 is being investigated in clinical trials for the treatment of advanced solid tumors and lymphomas.

Milataxel, a taxane that binds to and stabilizes tubulin, resulting in the inhibition of microtubule depolymerization. Milataxel has completed phase II clinical trials for non-small cell lung cancer patients, and for colorectal cancer patients. Besides, it was studied for malignant mesothelioma. However, the drug has been discontinued due to toxicity issues at the dose level of 35 mg/m 2.