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.

Fexofenadine is a second-generation, long lasting H1-receptor antagonist (antihistamine) which has a selective and peripheral H1-antagonist action. Histamine is a chemical that causes many of the signs that are part of allergic reactions, such as the swelling of tissues. Histamine is released from histamine-storing cells (mast cells) and attaches to other cells that have receptors for histamine. The attachment of the histamine to the receptors causes the cell to be "activated," releasing other chemicals which produce the effects that we associate with allergy. Fexofenadine blocks one type of receptor for histamine (the H1 receptor) and thus prevents activation of cells by histamine. Unlike most other antihistamines, Fexofenadine does not enter the brain from the blood and, therefore, does not cause drowsiness. Fexofenadine lacks the cardiotoxic potential of terfenadine, since it does not block the potassium channel involved in repolarization of cardiac cells. Fexofenadine is sold under the trade name Allegra among others. ALLEGRA is indicated for the relief of symptoms associated with seasonal allergic rhinitis in adults and children 2 years of age and older.

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.

Topotecan, a semi-synthetic derivative of camptothecin (a plant alkaloid obtained from the Camptotheca acuminata tree), is an anti-tumor drug with topoisomerase I-inhibitory activity similar to irinotecan. DNA topoisomerases are enzymes in the cell nucleus that regulate DNA topology (3-dimensional conformation) and facilitate nuclear processes such as DNA replication, recombination, and repair. During these processes, DNA topoisomerase I creates reversible single-stranded breaks in double-stranded DNA, allowing intact single DNA strands to pass through the break and relieve the topologic constraints inherent in supercoiled DNA. The 3'-DNA terminus of the broken DNA strand binds covalently with the topoisomerase enzyme to form a catalytic intermediate called a cleavable complex. After DNA is sufficiently relaxed and the strand passage reaction is complete, DNA topoisomerase reattaches the broken DNA strands to form the unaltered topoisomers that allow transcription to proceed. Topotecan interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal cells can be affected by the medicine, other effects may also occur. Unlike irinotecan, topotecan is found predominantly in the inactive carboxylate form at neutral pH and it is not a prodrug. Topotecan has the same mechanism of action as irinotecan and is believed to exert its cytotoxic effects during the S-phase of DNA synthesis. Topoisomerase I relieves torsional strain in DNA by inducing reversible single strand breaks. Topotecan binds to the topoisomerase I-DNA complex and prevents religation of these single strand breaks. This ternary complex interferes with the moving replication fork, which leads to the induction of replication arrest and lethal double-stranded breaks in DNA. As mammalian cells cannot efficiently repair these double strand breaks, the formation of this ternary complex eventually leads to apoptosis (programmed cell death). Topotecan mimics a DNA base pair and binds at the site of DNA cleavage by intercalating between the upstream (−1) and downstream (+1) base pairs. Intercalation displaces the downstream DNA, thus preventing religation of the cleaved strand. By specifically binding to the enzyme–substrate complex, Topotecan acts as an uncompetitive inhibitor. Topotecan is used for the treatment of advanced ovarian cancer in patients with disease that has recurred or progressed following therapy with platinum-based regimens. Also used as a second-line therapy for treatment-sensitive small cell lung cancer, as well as in combination with cisplatin for the treatment of stage IV-B, recurrent, or persistent cervical cancer not amenable to curative treatment with surgery and/or radiation therapy. Topotecan is sold under the trade name Hycamtin.

Docetaxel was protected by patents (U.S. patent and European patent) which were owned by Sanofi-Aventis, and so was available only under the Taxotere brand name internationally. The European patent expired in 2010. Docetaxel is a clinically well-established anti-mitotic chemotherapy medication used for the treatment of patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy. Also used as a single agent in the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of prior platinum-based chemotherapy. It is also used in combination with prednisone, in the treatment of patients with androgen independent (hormone refractory) metastatic prostate cancer. Furthermore, docetaxel has uses in the treatment of gastric adenocarcinoma and head and neck cancer. Docetaxel interferes with the normal function of microtubule growth. Whereas drugs like colchicine cause the depolymerization of microtubules in vivo, docetaxel arrests their function by having the opposite effect; it hyper-stabilizes their structure. This destroys the cell's ability to use its cytoskeleton in a flexible manner. Specifically, docetaxel binds to the β-subunit of tubulin. Tubulin is the "building block" of mictotubules, and the binding of docetaxel locks these building blocks in place. The resulting microtubule/docetaxel complex does not have the ability to disassemble. This adversely affects cell function because the shortening and lengthening of microtubules (termed dynamic instability) is necessary for their function as a transportation highway for the cell. Chromosomes, for example, rely upon this property of microtubules during mitosis. Further research has indicated that docetaxel induces programmed cell death (apoptosis) in cancer cells by binding to an apoptosis stopping protein called Bcl-2 (B-cell leukemia 2) and thus arresting its function.

Sodium phenylbutyrate is a salt of an aromatic fatty acid. The compound is used to treat urea cycle disorders, because its metabolites offer an alternative pathway to the urea cycle to allow excretion of excess nitrogen. Sodium phenylbutyrate is also a histone deacetylase inhibitor and chemical chaperone, leading respectively to research into its use as an anti-cancer agent and in protein misfolding diseases such as cystic fibrosis. It is used as adjunctive therapy for the management of chronic urea cycle disorders due to deficiencies in carbamylphosphate (CPS), ornithine transcarbamylase (OTC), or argininosuccinic acid synthetase. It is indicated in all neonatal- onset efficiency presenting within the first 28 days of life. Also indicated in patients with late-onset, presenting after the first month of life with a history of hyperammonemic encephalopathy. Sodium phenylbutyrate is a pro-drug and is rapidly metabolized to phenylacetate. Phenylacetate is a metabolically active compound that conjugates with glutamine via acetylation to form phenylacetylglutamine. The kidneys then excrete Phenylacetylglutamine. PBA (phenylbutyric acid) is absorbed from the intestine and converted by way of β-oxidation to the active moiety, phenylacetic acid (PAA). PAA is conjugated with glutamine in the liver and kidney by way of N-acyl coenzyme A-l-glutamine N-acyltransferase to form phenylacetylglutamine (PAGN). Like urea, PAGN incorporates two waste nitrogens and is excreted in the urine. On a molar basis, it is comparable to urea (each containing two moles of nitrogen). Therefore, phenylacetylglutamine provides an alternate vehicle for waste nitrogen excretion.

Irinotecan is an antineoplastic enzyme inhibitor primarily used in the treatment of colorectal cancer. Irinotecan is sold under the brand name Camptosar among others. CAMPTOSAR is a topoisomerase inhibitor indicated for: • First-line therapy in combination with 5-fluorouracil and leucovorin for patients with metastatic carcinoma of the colon or rectum. • Patients with metastatic carcinoma of the colon or rectum whose disease has recurred or progressed following initial fluorouracil-based therapy. Irinotecan is a derivative of camptothecin. Camptothecins interact specifically with the enzyme topoisomerase I, which relieves torsional strain in DNA by inducing reversible single-strand breaks. Irinotecan and its active metabolite SN-38 bind to the topoisomerase I-DNA complex and prevent religation of these single-strand breaks. Current research suggests that the cytotoxicity of irinotecan is due to double-strand DNA damage produced during DNA synthesis when replication enzymes interact with the ternary complex formed by topoisomerase I, DNA, and either irinotecan or SN-38. Mammalian cells cannot efficiently repair these double-strand breaks.

Zileuton is an asthma drug that differs chemically and pharmacologically from other antiasthmatic agents. It blocks leukotriene synthesis by inhibiting 5-lipoxygenase, an enzyme of the eicosanoid synthesis pathway. Current data indicates that asthma is a chronic inflammatory disorder of the airways involving the production and activity of several endogenous inflammatory mediators, including leukotrienes. Sulfido-peptide leukotrienes (LTC4, LTD4, LTE4, also known as the slow-releasing substances of anaphylaxis) and LTB4, a chemoattractant for neutrophils and eosinophils, are derived from the initial unstable product of arachidonic acid metabolism, leukotriene A4 (LTA4), and can be measured in a number of biological fluids including bronchoalveolar lavage fluid (BALF) from asthmatic patients. In humans, pretreatment with zileuton attenuated bronchoconstriction caused by cold air challenge in patients with asthma. Zileuton is a specific inhibitor of 5-lipoxygenase and thus inhibits leukotriene (LTB4, LTC4, LTD4, and LTE4) formation. Both the R(+) and S(-) enantiomers are pharmacologically active as 5-lipoxygenase inhibitors in in vitro systems. Leukotrienes are substances that induce numerous biological effects including augmentation of neutrophil and eosinophil migration, neutrophil and monocyte aggregation, leukocyte adhesion, increased capillary permeability, and smooth muscle contraction. These effects contribute to inflammation, edema, mucus secretion, and bronchoconstriction in the airways of asthmatic patients. Zileuton is marketed under the trade name ZYFLO.

Nilutamide is an antineoplastic hormonal agent primarily used in the treatment of prostate cancer. Nilutamide is a pure, nonsteroidal anti-androgen with affinity for androgen receptors (but not for progestogen, estrogen, or glucocorticoid receptors). Consequently, Nilutamide blocks the action of androgens of adrenal and testicular origin that stimulate the growth of normal and malignant prostatic tissue. Prostate cancer is mostly androgen-dependent and can be treated with surgical or chemical castration. To date, antiandrogen monotherapy has not consistently been shown to be equivalent to castration. The relative binding affinity of nilutamide at the androgen receptor is less than that of bicalutamide, but similar to that of hydroxuflutamide. Nilutamide competes with androgen for the binding of androgen receptors, consequently blocking the action of androgens of adrenal and testicular origin that stimulate the growth of normal and malignant prostatic tissue. This blockade of androgen receptors may result in growth arrest or transient tumor regression through inhibition of androgen-dependent DNA and protein synthesis. Nilutamide is used in combination with surgical castration for the treatment of metastatic prostate cancer involving distant lymph nodes, bone, or visceral organs (Stage D2). Nilutamide is sold under the brand names Nilandron (US), Anandron (CA)).

Nevirapine is a non-nucleoside reverse transcriptase inhibitor (nNRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). HIV-2 RT and eukaryotic DNA polymerases (such as human DNA polymerases alpha, beta, or sigma) are not inhibited by nevirapine. Nevirapine is, in general, only prescribed after the immune system has declined and infections have become evident. It is always taken with at least one other HIV medication such as Retrovir or Videx. The virus can develop resistance to nevirapine if the drug is taken alone, although even if used properly, nevirapine is effective for only a limited time. Nevirapine binds directly to reverse transcriptase (RT) and blocks the RNA-dependent and DNA-dependent DNA polymerase activities by causing a disruption of the enzyme's catalytic site. The activity of nevirapine does not compete with template or nucleoside triphosphates. Nevirapine is used for use in combination with other antiretroviral drugs in the ongoing treatment of HIV-1 infection.