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.

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.

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.

Entrectinib (previously known as RXDX-101, NMS-E628) is an investigational drug, potent inhibitor of ALK, ROS1, and, importantly, of TRK family kinases, which shows promise for therapy of tumors bearing oncogenic forms of these proteins. Entrectinib (RXDX-101) is a selective inhibitor for all three Trk receptor tyrosine kinases encoded by the three NTRK genes, as well as the ROS1 and ALKreceptor tyrosine kinases.This investigational drug is active at low nanomolar concentrations, allowing for once-daily oral administration to patients whose tumors have been shown to have gene rearrangements in NTRK, ROS1, or ALK. Nerviano Medical Sciences, the original sponsor for entrectinib (formerly referred to as NMS-1191372), initiated the first-in-human Phase 1 study ALKA-372-001 in Italy in October 2012. The study is currently ongoing in Italy. Entrectinib is currently being tested in a global phase 2 basket clinical trial called STARTRK-2. In the U.S., entrectinib has orphan drug designation and rare pediatric disease designation for the treatment of neuroblastoma and orphan drug designation for treatment of TrkA-, TrkB-, TrkC-, ROS1- and ALK-positive non-small cell lung cancer (NSCLC) and metastatic colorectal cancer (mCRC).

Triclabendazole, (brand name Avomec, Egaten, etc) is a member of the benzimidazole family of anthelmintics used to treat liver flukes, specifically fascioliasis and paragonimiasis. Triclabendazole used routinely since 1983 in veterinary practice for the treatment of fascioliasis. It was not used in humans until the 1989 epidemic of fascioliasis near the Caspian Sea when Iranian authorities approved the use of the veterinary formulation to treat the infection. Fasciolicidal not only against the adult worms present in the biliary ducts, but also against the immature larval stages of Fasciola migrating through the hepatic parenchyma. Triclabendazole is shown to penetrate into liver flukes by transtegumentary absorption followed by inhibition of the parasite's motility, probably related to the destruction of the microtubular structure, resulting in the death of the parasite; the immobilizing effect is paralleled by changes in the parasite's resting tegumental membrane potential, strongly inhibiting the release of proteolytic enzymes, a process that appears critical to the survival of the parasite. Side effects are generally few, but can include abdominal pain and headaches. Biliary colic may occur due to dying worms. While no harms have been found with use during pregnancy, triclabendazole has not been well studied in this population. Triclabendazole is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. It is not commercially available in the United States.

Pexidartinib (PLX3397) is a small-molecule receptor tyrosine kinase (RTK) inhibitor with potential antineoplastic activity. Pexidartinib binds to and inhibits phosphorylation of stem cell factor receptor (KIT), colony-stimulating factor-1 receptor (CSF1R) and FMS-like tyrosine kinase 3 (FLT3), which may result in the inhibition of tumor cell proliferation and down-modulation of macrophages, osteoclasts and mast cells involved in the osteolytic metastatic disease. FDA has granted Breakthrough Therapy Designation to pexidartinib (PLX3397) for the treatment of tenosynovial giant cell tumor (TGCT) where surgical removal of the tumor would be associated with potentially worsening functional limitation or severe morbidity. In addition to Breakthrough Therapy Designation, pexidartinib (PLX3397) has been granted Orphan Drug Designation by FDA for the treatment of pigmented villonodular synovitis (PVNS) and giant cell tumor of the tendon sheath (GCT-TS). It also has received Orphan Designation from the European Commission for the treatment of TGCT.

Lorlatinib is an investigational medicine that inhibits the anaplastic lymphoma kinase (ALK) and ROS1 proto-oncogene. Lorlatinib was specifically designed to inhibit tumor mutations that drive resistance to other ALK inhibitors. Lorlatinib has in vitro activity against ALK and number of other tyrosine kinase receptor related targets including ROS1, TYK1, FER, FPS, TRKA, TRKB, TRKC, FAK, FAK2, and ACK. Lorlatinib demonstrated in vitro activity against multiple mutant forms of the ALK enzyme, including some mutations detected in tumors at the time of disease progression on crizotinib and other ALK inhibitors. Moreover, lorlatinib possesses the capability to cross the blood-brain barrier, allowing it to reach and treat progressive or worsening brain metastases as well. Lorlatinib is a third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) indicated for the treatment of patients with ALK-positive metastatic non-small cell lung cancer (NSCLC) whose disease has progressed on a) the prior use of crizotinib and at least one other ALK inhibitor for metastatic disease, or b) the prior use of alectinib as the first ALK inhibitor therapy for metastatic disease, or c) the prior use of certinib as the first ALK inhibitor therapy for metastatic disease.

Tecovirimat (ST-246) is a low-molecular-weight compound (molecular weight = 376), that is potent (concentration that inhibited virus replication by 50% = 0.010 microM), selective (concentration of compound that inhibited cell viability by 50% = >40 microM), and active against multiple orthopoxviruses, including vaccinia, monkeypox, camelpox, cowpox, ectromelia (mousepox), and variola viruses. The antiviral activity is specific for orthopoxviruses and the compound does not inhibit the replication of other RNA- and DNA-containing viruses or inhibit cell proliferation at concentrations of compound that are antiviral. ST-246 targets vaccinia virus p37, a viral protein required for envelopment and secretion of extracellular forms of virus. The compound is orally bioavailable and protects multiple animal species from lethal orthopoxvirus challenge. rug substance and drug product processes have been developed and commercial scale batches have been produced using Good Manufacturing Processes (GMP). Human phase I clinical trials have shown that ST-246 is safe and well tolerated in healthy human volunteers. Based on the results of the clinical evaluation, once a day dosing should provide plasma drug exposure in the range predicted to be antiviral based on data from efficacy studies in animal models of orthopoxvirus disease.

Enasidenib, aslo known as AG-221 and CC-90007, is a potent and selective IDH2 inhibitor with potential anticancer activity (IDH2 = Isocitrate dehydrogenase 2). The mutations of IDH2 present in certain cancer cells result in a new ability of the enzyme to catalyze the NAPH-dependent reduction of α-ketoglutarate to R(-)-2-hydroxyglutarate (2HG). The production of 2HG is believed to contribute to the formation and progression of cancer. The inhibition of mutant IDH2 and its neoactivity is therefore a potential therapeutic treatment for cancer. Enasidenib is an orally available, selective, potent inhibitor of the mutated IDH2 protein, making it a highly targeted investigational medicine for the potential treatment of patients with cancers that harbor an IDH2 mutation. Enasidenib has received orphan drug and fast track designations from the U.S. FDA. Enasidenib mesylate is in phase II clinical trials for Solid tumours and phase III clinical trials for the treatment of acute myeloid leukaemia.

Naldemedine (Symproic) is an opioid antagonist indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain. Naldemedine is an opioid antagonist with binding affinities for mu-, delta-, and kappa-opioid receptors. Naldemedine functions as a peripherally-acting mu-opioid receptor antagonist in tissues such as the gastrointestinal tract, thereby decreasing the constipating effects of opioids. Naldemedine is a derivative of naltrexone to which a side chain has been added that increases the molecular weight and the polar surface area, thereby reducing its ability to cross the blood-brain barrier (BBB). Naldemedine is also a substrate of the P-glycoprotein (P-gp) efflux transporter. Based on these properties, the CNS penetration of naldemedine is expected to be negligible at the recommended dose levels, limiting the potential for interference with centrally-mediated opioid analgesia. Naldemedine was approved in 2017 in both the US and Japan for the treatment of Opioid-induced Constipation.