Peficitinib (formerly known as ASP015K) is a pyrrolo[2,3-b]pyridine derivative orally administered once-daily JAK inhibitor in development for the treatment of Rheumatoid Arthritis. In preclinical studied Peficitinib inhibited JAK1 and JAK3 with IC50 of 3.9 and 0.7 nM, respectively. Peficitinib also inhibited IL-2-dependent T cell proliferation in vitro and STAT5 phosphorylation in vitro and ex vivo. Furthermore, Peficitinib dose-dependently suppressed bone destruction and paw swelling in an adjuvant-induced arthritis model in rats via prophylactic or therapeutic oral dosing regimens.In clinical trials, Peficitinib treatment prescribed at 50, 100 and 150 mg amounts each showed statistically significantly higher ACR20 response rates compared to the placebo and response rates increased up to the 150 mg dosage. Adverse events included neutropenia, headache, and abdominal pain. The treatment-emergent adverse events occurring more frequently in the Peficitinib group compared with the placebo group included diarrhea, nasopharyngitis, and increased serum creatine phosphokinase activity. No cases of serious infections were reported. Herpes zoster occurred in four patients (two each in the peficitinib 25 and 100 mg cohorts). The authors concluded that treatment with peficitinib as monotherapy for 12 weeks in Japanese patients with moderate to severe RA is efficacious and showed an acceptable safety profile.

Mephedrone (4-methylmethcathinone) is a β-ketoamphetamine belonging to the family of synthetic cathinones, an emerging class of designer drugs known for their hallucinogenic and psychostimulant properties as well as for their abuse potential. Mephedrone is a stimulant of dopamine (DA) release and blocks its reuptake through its interaction with the dopamine transporter. Furthermore, it has some affinity for various 5-hydroxytryptamine (5-HT) receptor subtypes. Neurotoxic effect of mephedrone on 5-HT and DA systems remains controversial. Although some studies in animal models reported no damage to DA nerve endings in the striatum and no significant changes in brain monoamine levels, some others suggested a rapid reduction in 5-HT and DA transporter function. Persistent serotonergic deficits were observed after binge like treatment in a warm environment and in both serotonergic and dopaminergic nerve endings at high ambient temperature. Oxidative stress cytotoxicity and an increase in frontal cortex lipid peroxidation were also reported. Despite the re-classification of mephedrone as a Class B restricted substance by the United Kingdom and restrictive legislation by the United States, international policy regarding mephedrone control is still developing and interest in synthetic amphetamine-like drugs could drive the development of future mephedrone analogues.

LADARIXIN is a dual inhibitor of chemokine receptors CXCR1 and CXCR2. It inhibits human polymorphonuclear leukocyte (PMN) migration to chemokine CXCL8 in vitro and prevents PMN infiltration and tissue damage in several models of cerebral ischemia/reperfusion in vivo. It is under development for the treatment of type 1 diabetes.

LEVOFENFLURAMINE is a levorotatory enantiomer of fenfluramine, a substituted amphetamine which was formerly used to treat obesity. LEVOFENFLURAMINE has dopamine-antagonistic properties and, at high doses, increases dopamine concentrations in rat striatal dialysates. It is essentially inactive to reduce food intake in human subjects.

Arctigenin is a plant lignan extracted from Arctium lappa that has been shown to have estrogenic properties. In ER-positive MCF-7 cells, arctigenin efficiently inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cell migration and invasion. Arctigenin confers anti-metastatic effects by inhibiting MMP-9 and uPA via the Akt, NF-κB and MAPK signaling pathways on breast cancer, regardless of ER expression. Intake of arctigenin could be an effective supplement for breast cancer patients. Arctigenin is a phenylpropanoid dibenzylbutyrolactone lignan compound possessing antitumor, anti-inflammatory, anti-influenza, antioxidant, antibacterial, and hypoglycaemic activities. Arctigenin exhibited significant antiproliferative activity against CCRF-CEM cells after 72 h treatment with IC50 values of 1.21 ± 0.15 um. It arrested CCRF-CEM cells in the S phase. It induced apoptosis in CCRF-CEM cells in a concentration- and time-dependent manner. Arctigenin is a good candidate for the development of novel agents against T-cell lymphoma. Arctigenin has been found to act as an agonist of adiponectin receptor 1 (AdipoR1). Arctigenin is an antagonist of MR and effectively decreases the Na/K-ATPase 1 gene expression, thus highlighting its potential as an anti-hypertensive drug lead compound.

Mericitabine is a specific inhibitor of hepatitis C virus (HCV) replication that target NS5B polymerase. Mericitabine, a prodrug, is hydrolyzed in vivo to produce PSI-6130. It had been studied in phase II clinical trials for the treatment of chronic hepatitis C. However, while it showed a good safety profile in clinical trials, it was not sufficiently effective to be used as a standalone agent.

CGI-1842 (also known as JI-101) is an oral multi-kinase inhibitor that targets vascular endothelial growth factor receptor type 2 (VEGFR-2), platelet derived growth factor receptor β (PDGFR-β), and ephrin type-B receptor 4 that has been used in trials studying the treatment of Cancer, Colon Cancer, Neuroendocrine, Ovarian Cancer, and Advanced Solid Tumors. By targeting multiple angiogenesis signaling pathways in tumor vessel beds, CGI-1842 has the potential to inhibit multiple stages of tumor angiogenesis and thus enhance anti-tumor efficacy. In preclinical models, CGI-1842 induced concentration-dependent blocking of both EphB4- and VEGF-stimulated signaling pathways and has shown excellent antitumor activity. CGI-1842 is well tolerated in cancer patients and has shown impressive activity in Phase I clinical trials.

Orvepitant is a novel generation brain penetrant, selective and potent, small molecule NK-1 receptor antagonist. Orvepitant’s (GW823296) mode of action and developability characteristics made it a suitable development candidate for the treatment of common anxiety disorders, posttraumatic stress disorder and major depressive disorder. It’s in phase II clinical trials as an effective inhibitor of itch-associated response.

Tradipitant is a neurokinin 1 receptor antagonist. The dose of 50 mg of tradipitant given orally for 4 weeks was not superior to placebo in reducing itch intensity in patients with atopic dermatitis. However, in a subsequent study, in which a higher dose (85 mg) was administered for 8 weeks, significant antipruritic effect compared with placebo was recorded. Tradipitant is in phase III clinical trial for the treatment of atopic dermatitis and gastroparesis. Vanda Pharmaceuticals plans a phase III trial in Motion Sickness in 2019.

Pagoclone is an anxiolytic agent from the cyclopyrrolone family, related to better-known drugs such as the sleeping medication zopiclone. It binds with the roughly equivalent high affinity (0.7–9.1 nM) to the benzodiazepine binding site of human GABAA receptors containing either a α1, α2, α3 or α5 subunit. It is a partial agonist at α1-, α2- and α5-containing GABAA receptors and a full agonist at receptors containing a α3 subunit. Pagoclone produces anxiolytic effects with little sedative or amnestic actions at low doses.