Licarbazepine, (R)- is a hydroxy derivative of R-licarbazepine acetate. Eslicarbazepine acetate (ESL), or S-licarbazepine acetate (ESL), Licarbazepine, (R)- acetate and their racemic mixture, as well as other related compounds, were orally assessed in rats for anticonvulsant activity and compared with carbamazepine (CBZ) and oxcarbazepine (OXC). Metabolism of OXC and its derivatives varies considerably between species. Rats metabolize ESL to OXC with minimal (S)-licarbazepine or Licarbazepine, (R)- metabolites. Licarbazepine, (R)- undergoes a further oxidation to the trans-diol metabolite, demonstrating an increased predisposition to earlier inactivation. Administration of ESL and of eslicarbazepine significantly protected mice against Maximal electroshocks-induced seizures, whereas that of Licarbazepine, (R)- failed to provide protection. This finding raises doubts on the contribution of Licarbazepine, (R)- as an active anticonvulsant.

Daikenchuto (TU-100) is a traditional Japanese Kampo medicine composed of four crude drugs: dried Japanese pepper, processed ginger, ginseng radix and maltose powder. TU-100 is traditionally used in the treatment of chronic gastrointestinal disorders, and often prescribed to relieve abdominal pain, abdominal distention, Crohn’s disease, irritable bowel syndrome, adhesive ileus, and paralytic ileus. TU-100 improves gastrointestinal dysmotility and reduces serum CRP levels in patients with grade B liver damage after hepatectomy. TU-100 is an effective treatment option after hepatic resection in patients with liver cancer. Although the effects of TU-100 on gastrointestinal motility have been unexplored, recent studies have revealed its various other effects, including the following: firstly, an anti-inflammatory response through the selective inhibition of cyclooxygenase-2 (COX-2) and/or down-regulation of several inflammatory mediators such as tumor necrosis factor-a, interleukin-1b and endothelin-1; secondly, the prevention of bacterial translocation; and thirdly, the increase of gastrointestinal blood flow through the induction of calcitonin gene-related peptide (CGRP), substance P and vasoactive intestinal polypeptide (VIP). TU-100, which is manufactured by Tsumura & Co. (Tokyo, Japan), has been approved by the US Food and Drug Administration as an investigational drug, and several placebo-controlled double-blind trials have been launched in the US to investigate its use for constipation and Crohn’s disease. TU-100 was approved for manufacture as a prescription drug in 1986 by the Japanese Ministry of Health and Welfare and has been sold commercially as a prescription Kampo (a generic term for the system of traditional medicine that was developed in Japan after being introduced from China in the fourth century) drug in Japan for many years.

TAK-593 is an oral formulation containing a small-molecule receptor tyrosine kinase inhibitor of both vascular endothelial growth factor receptor 2 (VEGFR2) and platelet-derived growth factor receptor (PDGFR) with potential antineoplastic activity. TAK-593 selectively binds to and inhibits VEGFR and PDGFR, which may result in the inhibition of angiogenesis and tumor cell proliferation. It was in the phase I of clinical trial in subjects with nonhematologic advanced cancer and it was discontinued.

PLX8394 is a potent and selective inhibitor of B-Raf V600E (IC50 14 nM for WT and 3.8 nM for V600E mutant). Unlike vermurafenib, sorafenib and dabrafenib, PLX8394 does not cause paradoxical MAPK pathway activation. PLX8394 is under investigation in phase I/II of clinical trial for the treatment patients with advanced unresectable solid tumors.

Cipargamin is an experimental synthetic antimalarial molecule belonging to the spiroindolone class. It possesses both the potency (average IC50 of 550 pM against asexual blood-stage P. falciparum) and favorable pharmacokinetics (elimination half-life of ~24 hours in humans) needed for a single-dose cure, a feature that could help slow the onset of parasite resistance and that is not shared by existing, approved antimalarial drugs. KAE609 is also unique in its ability to block transmission to mosquitoes. Cipargamin is a parasite P-type ATPase4 inhibitor. Cipargamin in phase II clinical trials for the treatment of acute, uncomplicated malaria due to plasmodium falciparum monoinfection. Nausea was the most common reported adverse effect. The adverse events were generally mild and did not lead to any discontinuations of the drug.

SN38 (7-ethyl-10-hydroxy camptothecin) is a prominent and efficacious anticancer agent. It is poorly soluble in both water and pharmaceutically approved solvents; therefore, the direct formulation of SN38 in solution form is limited. SN38 is formed via hydrolysis of irinotecan by carboxylesterases and metabolized via glucuronidation by UGT1A1. Currently, the water soluble prodrug of SN38, irinotecan (CPT-11), is formulated as a low pH solution and is approved for chemotherapy. SN38 causes the strongest inhibition of DNA topoisomerase I, followed by CPT and then CPT-11. CPT-11 dose dependently shifts the position of relaxed DNA in the direction of nicked DNA, but SN38 and CPT shows no effect on the position of relaxed DNA. SN38 dose-dependently and time-dependently inhibit DNA synthesis. Respective IC50 values of SN38, in DNA synthesis is 0.077 uM.

JNJ-38877605 is an orally available, small molecule inhibitor of the proto-oncogene c-Met (hepatocyte growth factor receptor [HGFR]) with potential antineoplastic activity. c-Met inhibitor JNJ-38877605 selectively binds to c-Met, thereby inhibiting c-Met phosphorylation and disrupting c-Met signal transduction pathways. JNJ-38877605 was in Phase I clinical trials. Combined clinical and correlative preclinical studies suggest that renal toxicity of JNJ-38877605 is caused by the formation of species-specific insoluble metabolites. These observations preclude further clinical development of JNJ-38877605.

Lexanopadol is a potent ORL-1 agonist (opioid receptor like -1), nociceptin receptor agonists and opioid mu receptor agonists. Preliminary evidence suggests that targeting ORL-1 receptors may have synergistic effects with mu receptors hence enhancing the therapeutic profile of Lexanopadol in the treatment of pain. Lexanopadol is particularly suited for the management of moderate to severe chronic pain, including neuropathic pain. Lexanopadol hemicitrate is in phase II clinical trials for the treatment of pain. However there is no recent development reported.

Antienite oxalate is an anthelmintic agent. Antienite (R 8141) is a metabolite of antazonite (R 6438), which is about 4 times as active as the original compound. R 8141 is active as an anthelmintic in poultry and in rats.