BMN-673 (8R,9S) is the (8R,9S) enantiomer of BMN-673, known as talazoparib. BMN 673 is a novel inhibitor of nuclear enzyme poly (ADP-ribose) polymerase (PARP) with potential antineoplastic activity.

Encorafenib, also known as BRAFTOVI or LGX818, is an orally available mutated BRaf V600E inhibitor with potential antineoplastic activity, which was developed by Novartis. LGX818 possesses selective anti-proliferative and apoptotic activity in cells expressing BRAFV600E. In the A375 (BRAFV600E) human melanoma cell line LGX818 suppresses phospho-ERK (EC50 = 3 nM) leading to potent inhibition of proliferation (EC50 = 4 nM). No significant activity was observed against a panel of 100 kinases (IC50 > 900 nM) and LGX818 did not inhibit proliferation of > 400 cell lines expressing wild-type BRAF. On June 27, 2018, the Food and Drug Administration approved encorafenib and Binimetinib (BRAFTOVI and MEKTOVI, Array BioPharma Inc.) in combination for patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, as detected by an FDA-approved test. Encorafenib and binimetinib target two different kinases in the RAS/RAF/MEK/ERK pathway. Compared with either drug alone, co-administration of encorafenib and binimetinib result in greater anti-proliferative activity in vitro in BRAF mutation-positive cell lines and greater anti-tumor activity with respect to tumor growth inhibition in BRAF V600E mutant human melanoma xenograft studies in mice. In addition to the above, the combination of encorafenib and binimetinib acted to delay the emergence of resistance in BRAF V600E mutant human melanoma xenografts in mice compared with the administration of either drug alone. Encorafenib is in phase III for Metastatic Colorectal Cancer and in phase II for Relapsed or Refractory Multiple Myeloma.

Lutetium Lu 177 dotatate binds to somatostatin receptors with highest affinity for subtype 2 receptors (SSRT2). Upon binding to somatostatin receptor expressing cells, including malignant somatostatin receptor-positive tumors, the compound is internalized. The beta emission from Lu 177 induces cellular damage by formation of free radicals in somatostatin receptor-positive cells and in neighboring cells. LUTATHERA® (lutetium Lu 177 dotatate) is indicated for the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults.

Apalutamide (developmental code name ARN-509) is a selective and competitive androgen receptor inhibitor with IC50 of 16 nM, useful for prostate cancer treatment. Apalutamide binds to AR in target tissues thereby preventing androgen-induced receptor activation and facilitating the formation of inactive complexes that cannot be translocated to the nucleus. This prevents binding to and transcription of AR-responsive genes. This ultimately inhibits the expression of genes that regulate prostate cancer cell proliferation and may lead to an inhibition of cell growth in AR-expressing tumor cells. Apalutamide is currently in phase III clinical trials for castration-resistant prostate cancer.

Eravacycline, known as Xerava by Tetraphase Pharmaceuticals, is a fully synthetic fluorocycline antibiotic of the tetracycline class with activity against clinically significant gram-negative, gram-positive aerobic, and facultative bacteria. This includes most of those bacteria resistant to cephalosporins, fluoroquinolones, β-lactam/β-lactamase inhibitors, multidrug-resistant strains, and carbapenem-resistant Enterobacteriaceae, and the majority of anaerobic pathogens. It was first approved by the FDA on August 27, 2018. Eravacycline disrupts bacterial protein synthesis by binding to the 30S ribosomal subunit thus preventing the incorporation of amino acid residues into elongating peptide chains.

Stiripentol is an anticonvulsant drug used in the treatment of epilepsy. It recently proved to increase the GABAergic transmission in vitro in an experimental model of immature rat. Clinical studies were based on the fact that STP also acts as an inhibitor of CYP3A4, CYP1A2, and CYP2C19 in vivo in epileptic patients. Side effects are largely due to the increase in plasma concentrations of other anticonvulsants and can be reduced by lowering the dose of those drugs. Nausea and vomiting are particularly noted when used in combination with sodium valproate. It appears to increase the potency of phenobarbital, primidone, phenytoin, carbamazepine, clobazam and diazepam.

Prucalopride is a novel enterokinetic compound and is the first representative of the benzofuran class. Prucalopride is a potent, selective and specific serotonin 5-HT4 receptor (5-HT4-R) agonist. Prucalopride (Resolor®), a highly selective serotonin 5-HT4 receptor agonist, is indicated in the European Economic Area for the treatment of adults with chronic idiopathic constipation (CIC) in whom laxatives have failed to provide adequate relief.

Fostamatinib is a pro-drug of a Syk inhibitor R406 initially developed by Rigel Pharmaceuticals, but then in-licensed by AstraZeneca. It reached phase III of clinical trials for such diseases as Rheumatoid Arthritis and Immune Thrombocytopenic Purpura, however, AstraZeneca decided not to proceed with regulatory filings and return the rights to the compound to Rigel Pharmaceuticals. In 2018 the drug was approved by the FDA for treatment of chronic immune thrombocytopenia. Fostamatinib is being developed for Autoimmune Hemolytic Anemia (phase II), graft versus host disease (phase I) and ovarian cancer (phase I).

Avatrombopag is an orally bioavailable, small molecule thrombopoietin (TPO) receptor agonist that stimulates proliferation and differentiation of megakaryocytes from bone marrow progenitor cells resulting in increased production of platelets. Avatrombopag does not compete with TPO for binding to the TPO receptor and has an additive effect with TPO on platelet production. Avatrombopag was discovered by Yamanouchi Pharmaceutical, developed by AkaRx which late became acquired by Dova Pharmaceuticals. In 2018 avatrombopag was approved by the FDA for thrombocytopenia in adults with chronic liver disease scheduled to undergo a procedure.

Amifampridine (Firdapse), currently approved in the European Union, is the first and only approved drug for the symptomatic treatment of Lambert-Eaton Myasthenic Syndrome (LEMS) in adults, a rare autoimmune disease with the primary symptoms of muscle weakness. In LEMS, the body’s own immune system attacks connections between nerves and muscles and disrupts the ability of nerve cells to send signals to muscle cells. Amifampridine blocks voltage-dependent potassium channels, thereby prolonging pre-synaptic cell membrane depolarization. Prolonging the action potential enhances the transport of calcium into the nerve ending. The resulting increase in intracellular calcium concentrations facilitates exocytosis of acetylcholine containing vesicles, which in turn enhances neuromuscular transmission. Amifampridine phosphate has been granted Orphan Drug Designation and Breakthrough Therapy designation by the FDA for the treatment of Lambert-Eaton Myasthenic Syndrome (LEMS).