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.

Deutetrabenazine (trade name Austedo) is a vesicular monoamine transporter 2 (VMAT2) inhibitor indicated for the treatment of chorea associated with Huntington’s disease. The drug was developed by Auspex Pharmaceuticals and is being commercialized by Teva Pharmaceuticals. Deutetrabenazine is a deuterated derivative of tetrabenazine. The incorporation of deuterium in place of hydrogen at the sites of primary metabolism results in metabolic clearance being slowed, allowing less frequent dosing and better tolerability.

Niraparib (MK-4827) displays excellent PARP 1 and 2 inhibition. Inhibition of PARP in the context of defects in other DNA repair mechanisms provide a tumor specific way to kill cancer cells. Niraparib is in development with TESARO, under licence from Merck & Co, for the treatment of cancers (ovarian, fallopian tube and peritoneal cancer, breast cancer, prostate cancer and Ewing's sarcoma). Niraparib was characterized in a number of preclinical models before moving to phase I clinical trials, where it showed excellent human pharmacokinetics suitable for once a day oral dosing, achieved its pharmacodynamic target for PARP inhibition, and had promising activity in cancer patients. It is currently being tested in phase 3 clinical trials as maintenance therapy in ovarian cancer and as a treatment for breast cancer.

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.

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.

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.

Crisaborole is a topically administered, boron-containing, anti-inflammatory compound that inhibits the phosphodiesterase-4 (PDE4) activity and thereby suppresses the cytokine release of TNFalpha, IL-12, IL-23 and other cytokines. PDE4 is an an enzyme that converts the intracellular second messenger 3'5'-cyclic adenosine monophosphate (cAMP) into the active metabolite adenosine monophosphate (AMP). By inhibiting PDE4 and thus increasing levels of cAMP, crisaborole controls inflammation. The use of boron chemistry enabled synthesis of a low-molecular-weight compound (251 daltons), thereby facilitating effective penetration of crisaborole through human skin. Crisaborole is in clinical development for the topical treatment of psoriasis and being pursued for the topical treatment of atopic dermatitis. Preliminary studies in children and adults demonstrated favorable efficacy and safety profiles. Crisaborole may represent an anti-inflammatory option that safely minimizes the symptoms and severity of AD and that can be used for both acute and long-term management.