Momelotinib (CYT387) is an ATP-competitive small molecule that potently inhibits JAK1/JAK2 kinases. Momelotinib is developing by Gilead Sciences for the oral treatment of pancreatic and non-small cell lung cancers, and myeloproliferative disorders (including myelofibrosis, essential thrombocythaemia and polycythaemia vera).

Fruquintinib is a highly selective small molecule drug candidate that has been shown to inhibit VEGFR 24 hours a day via an oral dose, with lower off-target toxicities compared to other targeted therapies. Mechanistically, Fruquintinib selectively blocks VEGF-mediated receptor autophosphorylation, thus inhibiting endothelial cell proliferation and migration. In preclinical in vitro studies using a 32P-ATP assay, Fruquintinib selectively inhibited the tyrosine kinase activity associated with VEGFR-1, VEGFR-2, and VEGFR-3 at concentrations in the nanomolar range, but showed little inhibition against a panel of 254 kinases related to cell cycle or cell proliferation, including cyclin-dependent kinase (CDK1, 2, 5), the epidermal growth factor receptor (EGFR), the mesenchymal-epithelial transition factor (c-Met), and platelet-derived growth factor receptor β (PDGFRβ) kinase. In cellular assays, Fruquintinib potently inhibited VEGF-stimulated VEGFR phosphorylation and proliferation in human umbilical vein endothelial cells. Fruquintinib demonstrated potent antiangiogenic effect and anti-tumor activity in xenograft models of colon adenocarcinoma (HT-29), non-small cell lung cancer (NSCLC; NCI-H460), renal clear cell carcinoma (Caki-1), and gastric carcinoma (BGC823) in mice treated for 3 weeks. Fruquintinib is currently under joint development in China by Chi-Med and its partner Eli Lilly and Company (“Lilly”). Chi-Med and Lilly jointly announced top-line results from the FRESCO CRC trial on March 3, 2017. In addition, Fruquintinib is being studied in China in Phase III pivotal trial in non-small cell lung cancer (“NSCLC”), known as FALUCA; and a Phase II study using Fruquintinib combined with Iressa® (gefitinib) in the first-line setting for patients with advanced or metastatic NSCLC.

Bexagliflozin, also known as EGT1442, is a potent and selective SGLT2 inhibitor. Bexagliflozin is under investigation for the treatment of Type 2 Diabetes Mellitus. Bexagliflozin has been investigated for the treatment of Diabetes Mellitus and Type2 Diabetes Mellitus. Clinical studies have established that bexagliflozin significantly reduces blood glucose and glycated hemoglobin in subjects with diabetes. Treatment with bexagliflozin also induces weight loss and a reduction in systolic and diastolic blood pressure.

Remimazolam is an intravenous benzodiazepine sedative-hypnotic with rapid onset and offset of action. This compound undergoes organ-independent metabolism to an inactive metabolite. Like other benzodiazepines, remimazolam can be reversed with flumazenil to rapidly terminate sedation and anesthesia. Phase I and II clinical trials have shown that remimazolam is safe and effective when used for procedural sedation. Phase III clinical trials have been completed investigating efficacy and safety in patients undergoing bronchoscopy and colonoscopy. The developer of this drug has suggested that intensive care unit sedation (beyond 24 hours) could be another possible indication for further development, since it is unlikely that prolonged infusions or higher doses of remimazolam would result in accumulation and extended effect.

Amisulpride, a benzamide derivative, shows a unique therapeutic profile being atypical antipsychotic. At low doses, it enhances dopaminergic neurotransmission by preferentially blocking presynaptic dopamine D2/D3 autoreceptors. At higher doses, amisupride antagonises postsynaptic dopamine D2 and D3 receptors, preferentially in the limbic system rather than the striatum, thereby reducing dopaminergic transmission. In addition its antagonism at serotonin 5-HT7 receptors likely underlies the antidepressant actions. Amisulpride is approved for clinical use in treating schizophrenia in a number of European countries and also for treating dysthymia, a mild form of depression, in Italy.

Temsavir (BMS-626529) is an attachment inhibitor (AI) in clinical development (administered as prodrug BMS-663068) that binds to HIV-1 gp120. Temsavir displays in vitro activity against HIV-1 envelopes with C-C chemokine receptor type 5 (CCR5-), C-X-C chemokine receptor type 4 (CXCR4), and dual tropism. It also is active against almost all HIV-1 subtypes tested except for subtype CRF01-AE and possibly group O. Temsavir can inhibit both CD4-induced and CD4-independent formation of the "open state" four-stranded gp120 bridging sheet, and the subsequent formation and exposure of the chemokine co-receptor binding site. This unique mechanism of action prevents the initial interaction of HIV-1 with the host CD4+ T cell, and subsequent HIV-1 binding and entry. Temsavir is administered as a phosphonooxymethyl ester prodrug (BMS-663068), which was developed to improve the solubility and dissolution of Temsavir. Temsavir is currently being investigated clinically through the use of the prodrug BMS-663068, and a Phase III study of BMS-663068 in HIV-1-infected treatment-experienced subjects is ongoing (NCT02362503).

Selumetinib (AZD6244 or ARRY-142886) is a potent, selective, and ATP-uncompetitive inhibitor of Ras-Raf-mitogen-activated protein kinase kinase (MEK1/2). This inhibition can prevent ERK activation, disrupt downstream signal transduction, and inhibit cancer cell proliferation and survival. Selumetinib has shown tumour suppressive activity in multiple rodent models of human cancer including melanoma, pancreatic, colon, lung, and breast cancers. AstraZeneca is responsible for development and commercialization of selumetinib.

Lumateperone (ITI-722/ITI-007) is a dual 5HT2A receptor antagonist/dopamine phosphoprotein modulator (DPPM) for the treatment of schizophrenia. It is an orally available compound which combines potent 5HT2A receptor antagonism with cell-type-specific modulation of phosphoprotein pathways downstream of dopamine receptors. Lumateperone was developed by Intra-Cellular Therapies, Inc., and is being evaluated for the treatment of schizophrenia and bipolar depression. In 3 efficacy studies in patients with acute schizophrenia, lumateperone was well-tolerated with a favorable safety profile, and in 2 studies of 3 demonstrated significantly superior efficacy over placebo.

Tenapanor is an inhibitor of the sodium-proton (Na(+)/H(+)) exchanger NHE3 and reduces sodium absorption in the GI tract, thus increasing intestinal fluid. Ardelyx has completed Phase 3 development of tenapanor for the treatment of irritable bowel syndrome with constipation (IBS-C) and submitted a new drug application to the U.S. Food and Drug Administration for the treatment of patients with IBS-C. In addition, tenapanor successfully completed phase III clinical trial for the treatment of hyperphosphatemia in people with end-stage renal disease who are on dialysis and RDX013, a potassium secretagogue program for the potential treatment of high potassium, or hyperkalemia, a problem among certain patients with kidney and/or heart disease.

LASMIDITAN is a serotonin (5-HT) receptor agonist without vasoconstrictor activity, which selectively binds to the 5-HT(1F) receptor subtype. It is under development for the treatment of migraine.