Neratinib (HKI-272) is a pan-HER inhibitor, this irreversible tyrosine kinase inhibitor binds and inhibits the tyrosine kinase activity of epidermal growth factor receptors, EGFR (or HER1), HER2 and HER4, which leads to reduced phosphorylation and activation of downstream signaling pathways. Neratinib is a modified form of the discontinued compound pelitinib, and was originally being develoAdditionally, phase II development of oral neratinib as a neoadjuvant therapy for breast cancer, as a second-line therapy for non-small cell lung cancer, and for other solid tumours is also in progress in numerous countries worldwide. ped by Wyeth (later Pfizer). Oral neratinib is awaiting approval as an extended adjuvant therapy for breast cancer in the EU and in the US. Blocking HER2 function by a small molecule kinase inhibitor, such as neratinib, represents an attractive alternate strategy for the growth inhibition of HER2-positive tumours.

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.

Abemaciclib, previously known as LY2835219, is a potent and selective inhibitor of cyclin-dependent kinases: CDK4 and CDK6, developed by Eli Lilly, which is in clinical trial phase III for the treatment of breast cancer and non-small cell lung cancer (NSCLC) and in phase II for investigation of its treatment glioblastoma and melanoma.

Vaborbactam (formerly RPX7009) is a new beta-lactamase inhibitor based on a cyclic boronic acid pharmacophore. Vaborbactam is a highly active beta-lactamase inhibitor that restores activity of meropenem and other beta-lactam antibiotics in beta-lactamase-producing bacteria, particularly KPC-producing CRE. Meropenem in combination with vaborbactam (VABOMERE) is indicated for the treatment of patients 18 years and older with complicated urinary tract infections including pyelonephritis caused by designated susceptible bacteria. The vaborbactam component of VABOMERE is a non-suicidal beta-lactamase inhibitor that protects meropenem from degradation by certain serine beta-lactamases such as Klebsiella pneumoniae carbapenemase (KPC). Vaborbactam does not have any antibacterial activity. Vaborbactam does not decrease the activity of meropenem against meropenem-susceptible organisms.

Ertugliflozin (PF-04971729) is a potent and selective sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor incorporating a unique dioxa-bicyclo[3.2.1]octane (bridged ketal) ring system. SGLT2 has become an important therapeutic target and several SGLT2-selective inhibitors are either approved or in clinical development for the management of blood glucose in patients with type 2 diabetes. Ertugliflozin demonstrated robust urinary glucose excretion in rats and an excellent preclinical safety profile. It was announced that FDA and EMA filing acceptances of three marketing applications for ertugliflozin-containing medicines for adults with type 2 diabetes.

Telotristat (telotristat etiprate) is an ethyl ester prodrug which is hydrolyzed to its active moiety LP-778902 both in vivo and in vitro. Telotristat etiprate is an orally bioavailable, small-molecule, tryptophan hydroxylase (TPH) inhibitor. It is the first investigational drug in clinical studies to target TPH, an enzyme that triggers the excess serotonin production within metastatic neuroendocrine tumor (mNET) cells leading to carcinoid syndrome. Unlike existing treatments of carcinoid syndrome which reduce the release of serotonin outside tumor cells, telotristat etiprate reduces serotonin production within the tumor cells. By specifically inhibiting serotonin production telotristat may provide patients with more control over their disease. Telotristat etiprate has received Fast Track and Orphan Drug designation from the U.S. Food and Drug Administration and has been granted priority review by the FDA with a Prescription Drug User Fee Act (PDUFA) target action date of February 28, 2017.

Secnidazole (trade names Flagentyl, Sindose, Solosec) is a nitroimidazole derivative used to in the treatment of amoebiasis and bacterial vaginosis. Secnidazole and other 5-nitroimidazole drugs enter micro-organisms by passive diffusion and undergo activation by reduction of the 5-nitro group. In anaerobic micro-organisms, such as Trichomonas, Giardia and Entamoeba spp., this intracellular reduction occurs via the pyruvate ferredoxin oxidoreductase complex and results in a concentration gradient across the cell membrane which, in tum, enhances transport of the parent drug into the cell. Because the electron affinity of the 5-nitroimidazoles is greater than that of reduced ferredoxin, the drug interrupts the normal electron flow. Aerobic micro-organisms have a more positive redox potential (i.e. are more efficient electron acceptors) than secnidazole and other 5-nitroimidazoles, which explains the selective toxicity of these drugs against anaerobic microorganisms. DNA is the intracellular target of the Secnidazole and other 5-nitroimidazoles. Secnidazole and other 5-nitroimidazoles possess selective activity against many anaerobic Gram-positive and Gram-negative bacteria and protozoa. In general, secnidazole and metronidazole were approximately equipotent in activity against Bacteroides fragilis, Trichomonas vaginalis, and Entamoeba histolytica, in in vitro studies. Secnidazole is rapidly and completely absorbed after oral administration. Plasma drug concentrations are linear over the therapeutic dose range of 0.5 to 2g. The tolerability profile of secnidazole does not differ markedly from other 5-nitroimidazoles. The most commonly reported adverse events in clinical trials involved the gastrointestinal tract (nausea, vomiting, glossitis, anorexia, epigastric pain and a metallic taste) and occurred in 2 to 10% of patients. A headache and dizziness were experienced by about 2% of patients. The drug was equally well tolerated in adults and children, and no adverse event required therapeutic intervention or treatment withdrawal.

Lifitegrast (under brand name Xiidra) was approved as an ophthalmic solution for the treatment of the signs and symptoms of dry eye disease. Lifitegrast binds to the integrin lymphocyte function-associated antigen-1 (LFA-1); a cell surface protein found on leukocytes and blocks the interaction of LFA-1 with its cognate ligand intercellular adhesion molecule-1 (ICAM-1). This LFA-1/ICAM-1 interaction is a key step in the inflammatory cascade that contributes to dry eye disease. Besides lifitegrast participates in phase II clinical trials for prevention of the signs and symptoms of allergic conjunctivitis.

Venetoclax (trade name Venclexta, also known as ABT-199) is a selective and orally bioavailable small-molecule inhibitor of BCL-2, an antiapoptotic protein. BCL-2 and its related proteins BCL-XL and MCL-1 bind to and sequester pro-apoptotic signals in the cell, causing a down-regulation of apoptosis. As an oncogene and an important regulator of apoptosis, BCL-2 overexpression therefore results in increased tumor cell survival and resistance to chemotherapy. FDA approved Venetoclax in April 2016 for the treatment of patients with chronic lymphocytic leukemia (CLL) with 17p deletion, as detected by an FDA approved test, who have received at least one prior therapy. Also this drug in phase 3 clinical trial in combination therapy for the treatment patients with refractory myeloma and Acute Myeloid Leukemia. Common side effects include neutropenia, nausea, anemia, diarrhea, upper respiratory tract infection. Major side effects include tumor lysis syndrome and severe neutropenia.

Rucaparib is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated for the treatment of advanced mutant BRCA ovarian cancer. Rucaparib is being investigated in clinical trials against prostate cancer, breast cancer and other neoplasms.