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.

Oritavancin is an glycopeptide antibiotic with bactericidal activity effective in treating infections caused by Gram-positive organisms. It treats complicated skin and skin structure infections. This drug demonstrates similar activity to vancomycin, but it has stronger activity against Staphylococcus and Enterococcus. The pharmacokinetics and pharmacodynamics of oritavancin appear to be favourable and once-daily dosing is likely. The incidence of multi-drug resistant bacteria is increasing and explorations into additional treatment options are essential. Oritavancin is marketed under the brand name Orbactiv. Orbactiv is indicated for the treatment of adult patients with acute bacterial skin and skin structure infections caused or suspected to be caused by susceptible isolates of designated Gram-positive microorganisms. Oritavancin has the following mechanism of action: 1) Inhibition of the transglycosylation (polymerisation) step of cell wall biosynthesis by binding to the stem peptide of peptidoglycan precursors 2) Inhibition of the transpeptidation (crosslinking) step of cell wall biosynthesis by binding to the peptide bridging segments of the cell wall 3) Disruption of bacterial membrane integrity, leading to depolarisation, increased permeability and rapid cell death.

Alvimopan (LY246736, ADL 8-2698, trade name Entereg) is a potent, peripherally selective mu-opioid receptor antagonist. Alvimopan was developed by Adolor Corporation (now Cubist Pharmaceuticals) and GlaxoSmithKline for the treatment of postoperative ileus. Postoperative ileus is the impairment of gastrointestinal motility after intra-abdominal surgery or other non-abdominal surgeries. This may potentially delay gastrointestinal recovery and hospital discharge until its resolution. Morphine and other mu-opioid receptor agonists are universally used for the treatment of acute postsurgical pain; however, they are known to have an inhibitory effect on gastrointestinal motility and may prolong the duration of postoperative ileus. Following oral administration, alvimopan antagonizes the peripheral effects of opioids on gastrointestinal motility and secretion by competitively binding to gastrointestinal tract mu-opioid receptors.

Anidulafungin (brand names Eraxis (in U.S. and Russia) and Ecalta (in Europe)) is a semi-synthetic echinocandin with antifungal activity and it is active in vitro against many Candida, as well as some Aspergillus. Like other echinocandins, anidulafungin is not active against Cryptococcus neoformans, Trichosporon, Fusarium, or zygomycetes. This drug is indicated for the treatment of candidemia and the following Candida infections: intra-abdominal abscess and peritonitis; and for the treatment of esophageal candidiasis. Anidulafungin inhibits glucan synthase, an enzyme present in fungal, but not mammalian cells. This results in inhibition of the formation of 1,3--D-glucan, an essential component of the fungal cell wall.

Duloxetine (brand names Cymbalta, Yentreve, and in parts of Europe, Xeristar or Ariclaim) is indicated for the acute and maintenance treatment of major depressive disorder (MDD), as well as acute management of generalized anxiety disorder. Also used for the management of neuropathic pain associated with diabetic peripheral neuropathy, and fibromyalgia. Has been used in the management of moderate to severe stress urinary incontinence (SUI) in women. It is manufactured and marketed by Eli Lilly and Company. Duloxetine has not yet been FDA approved for stress urinary incontinence or for fibromyalgia. Duloxetine is a selective SNRI (selective serotonin-norepinephrine reuptake inhibitor). Duloxetine is a systemic drug therapy which affects the body as a whole. Known also under the code name LY248686, it is a potent dual reuptake inhibitor of serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine (NE), possessing comparable affinities in binding to NE- and 5-HT transporter sites. It is a less potent inhibitor of dopamine reuptake.

Pemetrexed is a new-generation antifolate, approved for the treatment of mesothelioma and non-small cell lung cancer, currently being evaluated for the treatment of a variety of other solid tumors. Pemetrexed, is a folate analog metabolic inhibitor that exerts its action by disrupting folate-dependent metabolic processes essential for cell replication. In vitro studies have shown that pemetrexed inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR), glycinamide ribonucleotide formyltransferase (GARFT) and and to a lesser extent aminoimidazole carboxamide ribonucleotide formyltransferase (AICARFT), which are folate-dependent enzymes involved in the de novo biosynthesis of thymidine and purine nucleotides. Pemetrexed is taken into cells by membrane carriers such as the reduced folate carrier and membrane folate binding protein transport systems. Once in the cell, pemetrexed is converted to polyglutamate forms by the enzyme folylpolyglutamate synthetase. The polyglutamate forms are retained in cells and are inhibitors of TS and GARFT. Polyglutamation is a time- and concentration-dependent process that occurs in tumor cells and, is thought to occur to a lesser extent, in normal tissues. Polyglutamated metabolites are thought to have an increased intracellular half-life resulting in prolonged drug action in malignant cells.

NAMENDA (marketed under the brands Namenda among others) is an N-methyl-D-aspartate (NMDA) receptor antagonist indicated for the treatment of moderate to severe dementia of the Alzheimer’s type. Persistent activation of central nervous system N-methyl-D-aspartate (NMDA) receptors by the excitatory amino acid glutamate has been hypothesized to contribute to the symptomatology of Alzheimer’s disease. Memantine is postulated to exert its therapeutic effect through its action as a low to moderate affinity uncompetitive (open-channel) NMDA receptor antagonist which binds preferentially to the NMDA receptor-operated cation channels. There is no evidence that memantine prevents or slows neurodegeneration in patients with Alzheimer’s disease. Memantine showed low to negligible affinity for GABA, benzodiazepine, dopamine, adrenergic, histamine and glycine receptors and for voltage-dependent Ca2+, Na+ or K+ channels. Memantine also showed antagonistic effects at the 5HT3 receptor with a potency similar to that for the NMDA receptor and blocked nicotinic acetylcholine receptors with one-sixth to one-tenth the potency. In vitro studies have shown that memantine does not affect the reversible inhibition of acetylcholinesterase by donepezil, galantamine, or tacrine.

Atomoxetine is indicated for the treatment of Attention-Deficit/Hyperactivity Disorder. The precise mechanism by which atomoxetine produces its therapeutic effects in Attention-Deficit/Hyperactivity Disorder (ADHD) is unknown, but is thought to be related to selective inhibition of the pre-synaptic norepinephrine transporter. Most common adverse reactions are: nausea, vomiting, fatigue, decreased appetite, abdominal pain, and somnolence, constipation, dry mouth, dizziness, erectile dysfunction, and urinary hesitation. Atomoxetine is a substrate for CYP2D6 and hence concurrent treatment with CYP2D6 inhibitors such as bupropion (Wellbutrin) or fluoxetine (Prozac) is not recommended, as this can lead to significant elevations of plasma atomoxetine levels.

Raloxifene (marketed as Evista by Eli Lilly and Company) is an oral selective estrogen receptor modulator (SERM) that has estrogenic actions on bone and anti-estrogenic actions on the uterus and breast. Raloxifene binds to estrogen receptors, resulting in differential expression of multiple estrogen-regulated genes in different tissues. Raloxifene produces estrogen-like effects on bone, reducing resorption of bone and increasing bone mineral density in postmenopausal women, thus slowing the rate of bone loss. The maintenance of bone mass by raloxifene and estrogens is, in part, through the regulation of the gene-encoding transforming growth factor-β3 (TGF-β3), which is a bone matrix protein with antiosteoclastic properties. Raloxifene activates TGF-β3 through pathways that are estrogen receptor-mediated but involve DNA sequences distinct from the estrogen response element. The drug also binds to the estrogen receptor and acts as an estrogen agonist in preosteoclastic cells, which results in the inhibition of their proliferative capacity. This inhibition is thought to contribute to the drug's effect on bone resorption. Other mechanisms include the suppression of the activity of the bone-resorbing cytokine interleukin-6 promoter activity. Raloxifene also antagonizes the effects of estrogen on mammary tissue and blocks uterotrophic responses to estrogen. By competing with estrogens for the estrogen receptors in reproductive tissue, raloxifene prevents the transcriptional activation of genes containing the estrogen response element. As well, raloxifene inhibits the estradiol-dependent proliferation of MCF-7 human mammary tumor cells in vitro. The mechanism of action of raloxifene has not been fully determined, but evidence suggests that the drug's tissue-specific estrogen agonist or antagonist activity is related to the structural differences between the raloxifene-estrogen receptor complex (specifically the surface topography of AF-2) and the estrogen-estrogen receptor complex. Also, the existence of at least 2 estrogen receptors (ERα, ERβ) may contribute to the tissue specificity of raloxifene. Raloxifene is indicated for the treatment and prevention of osteoporosis in postmenopausal women. It is also used for reduction of risk and treatment of invasive breast cancer, and it also reduces breast density. For either osteoporosis treatment or prevention, supplemental calcium and/or vitamin D should be added to the diet if daily intake is inadequate. Common adverse events considered to be drug-related were hot flashes and leg cramps.

Olanzapine is a novel antipsychotic agent marketed by Lilly & Co. It has a pleotrophic pharmacology and affects dopaminergic, serotonergic, muscarinic and adrenergic activities. Olanzapine is used to treat the symptoms of psychotic conditions such as schizophrenia and bipolar disorder (manic depression) in adults and children who are at least 13 years old. Olanzapine is sometimes used together with other antipsychotic medications or antidepressants. The mechanism of action of olanzapine, as with other drugs having efficacy in schizophrenia, is unknown. However, it has been proposed that this drug’s efficacy in schizophrenia is mediated through a combination of dopamine and serotonin type 2 (5HT2) antagonism. The mechanism of action of olanzapine in the treatment of acute manic or mixed episodes associated with bipolar I disorder is unknown. Olanzapine treatment led to rapid phosphorylation of kinases from all three pathways in PC12 cells. Phosphorylation of Akt was blocked with selective inhibitors (wortmannin and LY294002), which implicates phosphoinositide 3-kinase (PI3K) in the signaling cascade. Short-term mitogenic effects of olanzapine were abolished with a selective inhibitor of Akt, but not by inhibition of the ERK pathway. Olanzapine is metabolized by the cytochrome P450 system; principally by isozyme 1A2 and to a lesser extent by 2D6. By these mechanisms more than 40% of the oral dose, on average, is removed by the hepatic first-pass effect. Drugs or agents that increase the activity of CYP1A2, notably tobacco smoke, may significantly increase hepatic first-pass clearance of Olanzapine; conversely, drugs which inhibit 1A2 activity (examples: Ciprofloxacin, Fluvoxamine) may reduce Olanzapine clearance. The most common side effects appear to be somnolence and weight gain. About 11% of patients gain weight -especially if on a high starting dose and if they were underweight pre-treatment. Sexual dysfunction is a problem for many patients, although sexual dysfunction in schizophrneia does not appear to be primarily attributable to drugs.