Vonoprazan (Vonoprazan fumarate or TAK-438) under brand name Takecab, discovered by Takeda, is a new medicine for treating acid-related diseases with a novel mechanism of action called potassium-competitive acid blockers (P-CABs) which competitively inhibits the binding of potassium ions to H+,K+-ATPase (also known as the proton pump) in the final step of gastric acid secretion in gastric parietal cells. The drug is approved in Japan for the treatment of acid-related diseases, including gastric ulcer, duodenal ulcer, reflux esophagitis and Adjunct to Helicobacter pylori eradication in the case of Helicobacter pylori gastritis.

Vericiguat, discovered at Bayer, is the first soluble guanylate cyclase (sGC) stimulator. Vericiguat is currently being studied in a Phase III clinical program for the treatment of heart failure with reduced ejection fraction (HFrEF).

OTL-0038 or OTL-38, a fluorescent-labelled folate receptor-α (FRα) targeted imaging agent that accumulates in vivo in tumor cells expressing FR. OTL38 is currently in ongoing Phase 3 clinical trial in ovarian cancer and successfully completed phase 2 clinical trial in lung cancer. OTL38 is being evaluated for its ability to help surgeons locate and remove hard-to-find cancerous lesions that are often widespread. In 2014, the OTL-38 molecule was granted orphan drug status which can be given to the maker of a drug that treats rare conditions or diseases and offers protection from competition for a period of time. In addition, OTL-38 was studied in phase II clinical trials in the Netherlands for the diagnosis of endometriosis.

KX-01 is a dual inhibitor of Src kinase and tubulin polymerization. KX01 promotes the induction of p53, G2/M arrest of proliferating cell populations and subsequent apoptosis via the stimulation of Caspase-3 and PARP cleavage. The drug was developed by Kinex Pharmaceuticals and reached phase II of clinical trials for the treatment of Castration-Resistant Prostate Cancer and Actinic Keratosis. KX-01 demonstrated good in vitro pofile against different cancer cell lines with IC50 in nanomolar range.

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.

Allopregnanolone is a neurosteroid metabolite of progesterone. It is an allosteric modulator of inhibitory γ-aminobutyric acid (GABA-A) receptors on neural stem cells and other cell types in the brain. Allopregnanolone has effects similar to those of other positive allosteric modulators of the GABA action at GABAA receptor such as the benzodiazepines, including anxiolytic, sedative, and anticonvulsant activity. A solution of allopregnanolone, SAGE-547 is an intravenous allosteric modulator of both synaptic and extrasynaptic γ-aminobutyric acid type A (GABAA)receptors. It's believed that allopregnanolone is effective as an anticonvulsant when prolonged seizure activity has become resistant to benzodiazepine treatment. Under the names brexanolone and SAGE-547, allopregnanolone is under development by SAGE Therapeutics as an intravenously administered drug for the treatment of super-refractory status epilepticus, postpartum depression, and essential tremor. Allopregnanolone is in phase III trials for the treatment of super-refractory status epilepticus (SRSE) and postpartum depression.

Alpelisib (BYL719) is a PI3Kα-selective inhibitor. PI3K-AKT-mTOR pathway is frequently activated in cancer, therefore investigational PI3K inhibitor alpelisib is considered to be effective as an anticancer agent and has been in clinical development by Novartis. Alpelisib have demonstrated activity in preclinical models of solid tumors and had favorable tolerability profiles, with the most common adverse events consistent with “on-target” inhibition of PI3K in early clinical studies. There are ongoing clinical trials of alpelisib in a range of cancer types, including breast cancer, head and neck squamous cell carcinoma, non-small cell lung carcinoma, lymphoma, and glioblastoma multiforme. Combination therapy with other chemo therapeutics may be preferable.

Lofexidine is newly FDA approved in the United States under the brand name LUCEMYRA for the treatment of opioid withdrawal symptoms in adults. Lofexidine acts as an agonist to α2 adrenergic receptors. These receptors inhibit adenylyl cyclase activity, leading to the inhibition of the second messenger, cyclic adenosine monophosphate (cAMP). The inhibition of cAMP leads to potassium efflux through calcium-activated channels, blocking calcium ions from entering the nerve terminal, resulting in suppression of neural firing, inhibition of norepinephrine release. Lofexidine replaces the opioid-driven inhibition of cAMP production and moderating the symptoms of opioid withdrawal.

Migalastat (Galafold)-a small molecule drug developed by Amicus Therapeutics that restores the activity of specific mutant forms of α-galactosidase-has been approved for the treatment of Fabry disease in the EU in patients with amenable mutations. Migalastat attaches to certain unstable forms of alpha-galactosidase A, stabilising the enzyme. This allows the enzyme to be transported into areas of the cell where it can break down GL-3. Under the trade name Galafold (formerly known as Amigal), Migalastat is used to treat patients aged 16 years or over with Fabry disease. Because the number of patients with Fabry disease is low, the disease is considered ‘rare’, and the US Food and Drug Administration (FDA) assigned Galafold orphan drug status in 2004, and the European Committee for Medicinal Products for Human Use (CHMP) followed in 2006.

Tezacaftor (VX-661) is an investigational compound developed by Vertex Pharmaceuticals to treat cystic fibrosis (CF). It is an oral corrector of the CF transmembrane regulator (CFTR) and is similar to lumacaftor, another N-aryl-1-(2,2-difluoro-1,3-benzodioxol-5-yl)cyclopropanecarboxamide derivative developed by Vertex. Cystic fibrosis is caused by defects in CFTR gene, which encodes an epithelial chloride channel. The most common mutant Δ508CFTR is a misfolded protein that does not reach the cell membrane. VX-661 corrects trafficking of Δ508CFTR and partially restores chloride channel activity. In vitro, a combination of VX-661 and ivacaftor, an FDA approved in 2012 CFTR potentiator which increases the time the CFTR channel is open, allowing chloride ions to flow through the CFTR proteins on the surface of epithelial cells, resulted in greater CFTR activity compared with VX-661 alone. In February 2012, a phase 2, double-blind, placebo-controlled study of VX-661 was initiated in CF patients who were homozygous or heterozygous for the F508del mutation. There is an ongoing Vertex Phase 3 development program of VX-661 in combination with ivacaftor which includes four studies on CF patients 1) with two copies of the F508del mutation, 2) one copy of the F508del mutation and a second mutation that results in residual CFTR function, 3) one copy of the F508del mutation and a second mutation that results in residual CFTR function gating defect in the CFTR protein and 4) one copy of the F508del mutation and a second mutation that results in minimal CFTR function.