Pitolisant (INN) or tiprolisant (USAN) is a histamine receptor inverse agonist/antagonist selective for the H3 subtype. It has stimulant and nootropic effects in animal studies and may have several medical applications, having been researched for the treatment of narcolepsy, for which it has been granted orphan drug status in the EU and US. It is currently in clinical trials for schizophrenia and Parkinson’s disease. Pitolisant hydrochloride was approved by European Medicine Agency (EMA) on Mar 31, 2016. It was developed and marketed as Wakix® by Bioprojet in EU. Wakix® is available as the tablet for oral use, containing 4.5 mg and 18 mg of Pitolisant hydrochloride. The initial dose of 9 mg (two 4.5 mg, tablets) per day, and it should be used at the lowest effective dose, depending on individual patient response and tolerance, according to an up-titration scheme, without exceeding the dose of 36 mg/day. Pitolisant was the first clinically used H3 receptor inverse agonist.

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.

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.

Upadacitinib (ABT-494) is a Janus kinase 1 (JAK1) inhibitor currently being developed by AbbVie for the treatment of rheumatoid arthritis (RA), Crohn’s disease, ulcerative colitis, atopic dermatitis, and psoriatic arthritis. It is also being investigated as a potential treatment for people with active ankylosing spondylitis (AS). Currently, upadacitinib is being evaluatedin six global phase III studies in RA and twophase III studies in psoriatic arthritis (PsA), inaddition to phase II studies in Crohn’s disease and atopicdermatitis and a combined phase II/III study inulcerative colitis. Upadacitinib is a potent and selective Janus kinase (JAK) 1 inhibitor with an IC50 of 43 nM.

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.

Elagolix (ABT-620) is an oral gonadotropin-releasing hormone antagonist being studied for the treatment of endometriosis and uterine fibroids. The U.S. Food and Drug Administration (FDA) approved AbbVie's elagolix under the brand name Orilissa as the first and only oral gonadotropin-releasing hormone (GnRH) antagonist specifically developed for women with moderate to severe endometriosis pain.

Revefenacin (trade name Yupelri is a long-acting muscarinic antagonist developed by Mylan Ireland ltd for the treatment of chronic obstructive pulmonary disease (COPD). It has similar affinity to the subtypes of muscarinic receptors M1 to M5. In the airways, it exhibits pharmacological effects through inhibition of M3 receptor at the smooth muscle leading to bronchodilation. The competitive and reversible nature of antagonism was shown with human and animal origin receptors and isolated organ preparations. In preclinical in vitro as well as in vivo models, prevention of methacholine- and acetylcholine-induced bronchoconstrictive effects was dose-dependent and lasted longer than 24 hours.

Duvelisib (IPI-145), is an orally available, small-molecule, selective dual inhibitor of phosphatidylinositol 3 kinase (PI3K) δ and γ isoforms originated by Intellikine (owned by Takeda) and developed by Infinity Pharmaceuticals. Orally administered duvelisib was rapidly absorbed, with a dose-proportional increase in exposure. The compound produced a half-life of approximately 7-12 hours, following 14 days of dosing. Duvelisib exerts profound effects on adaptive and innate immunity by inhibiting B and T cell proliferation, blocking neutrophil migration, and inhibiting basophil activation. Duvelisib blockade of PI3K-δ and PI3K-γ potentially lead to significant therapeutic effects in multiple inflammatory, autoimmune, and hematologic diseases. The molecule is in phase III development as a combination therapy for patients with haematological malignancies such as chronic lymphocytic leukemia and follicular lymphoma.

Baricitinib (trade name Olumiant) is an investigational drug for rheumatoid arthritis (RA), being developed by Incyte and Eli Lilly. Baricitinib is a selective JAK1 and JAK2 inhibitor with IC50 of 5.9 nM and 5.7 nM in cell-free assays. In February 2017 Baricitinib was approved for use in the European Union as a second-line therapy for moderate to severe active rheumatoid arthritis in adults, either alone or in combination with methotrexate. On 31 May 2018 FDA approved Barictinib for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more TNF antagonist therapies.

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.