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.

PF-04965842 is an orally administered selective Janus kinase 1 (JAK1) inhibitor. PF-04965842 is currently in clinical trials for the treatment of autoimmune diseases.

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).

Osilodrostat (INN, USAN) (developmental code name LCI-699) is an orally active, non-steroidal corticosteroid biosynthesis inhibitor which is under development by Novartis for the treatment of Cushing's syndrome and pituitary ACTH hypersecretion (a specific subtype of Cushing's syndrome). Osilodrostat specifically acts as a potent and selective inhibitor of aldosterone synthase (CYP11B2) and at higher dosages of 11β-hydroxylase (CYP11B1). Osilodrostat decreases plasma and urinary aldosterone levels and rapidly corrects hypokalemia, in patients with primary aldosteronism and hypertension. At doses ≥1 mg o.d. Osilodrostat markedly increases 11-deoxycortisol plasma levels and blunts ACTH-stimulated cortisol release in ≈20% of patients, consistent with the inhibition of CYP11B1. In patients with resistant hypertension, Osilodrostat produces a non-significant reduction in blood pressure, possibly due to the increase in 11-deoxycortisol levels and the stimulation of the hypothalamic-pituitary-adrenal feedback axis. Because of the lack of selectivity, poor antihypertensive effect, and short half-life, the development of Osilodrostat as antihypertensive was halted. As of 2017, Osilodrostat is in phase III and phase II clinical trials for the treatment of pituitary ACTH hypersecretion and Cushing's syndrome, respectively.

GBT440 (previously GTx011) is a potent and direct drug for sickle cell treatment. In sickle cell anemia, abnormal hemoglobin molecules are formed, which causes problems for the flow of blood and oxygen through the body. GBT440 can selectively bind to hemoglobin, thereby increasing its affinity for oxygen. By inhibiting hemoglobin polymerization, it also prevents deformation of the red blood cells. GBT440, renamed Voxelotor, is thought to help prevent sickle cells blocking blood vessels, and therefore reduces pain (sickle cell crisis) experienced by patients. GBT440 is well absorbed following intravenous and oral administration, and quickly partitions into the red blood cell with a small part re‐distributed into the plasma. GBT440 was well tolerated in a randomized, placebo‐controlled, double blind, parallel group phase I/II study in healthy volunteers and sickle cell disease patients. Headache is the most reported adverse event related to the use of this drug, and no serious adverse events are known. A phase 3 clinical trial examining the efficacy and safety of the drug (compared to placebo) is planned to be completed in 2019. Voxelotor was also studied as a potential therapy for treatment of low oxygen levels in the blood of idiopathic pulmonary fibrosis patients, but this program was discontinued because of a lack of clinical benefits.

LEFAMULIN is a pleuromutilin antibiotic under development for the treatment of community-acquired bacterial pneumonia, as well as acute bacterial skin and skin structure infections. It inhibits bacterial protein synthesis by binding to the peptidyl transferase center of the 50S ribosome, resulting in the cessation of bacterial growth.

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.

Trifarotene is a novel first-in-class fourth-generation topical retinoid. It is a potent and selective RAR gamma-agonist. In multiple mouse models, trifarotene exhibited superior comedolytic, anti-inflammatory and depigmenting activity compared with other topical retinoids. In this 52-week study, trifarotene was safe, well-tolerated and effective in moderate facial and truncal acne. Trifarotene is in phase II clinical trial for the treatment of ichthyosis.