Mifamurtide (liposomal muramyl tripeptide phosphatidylethanolamine; trade name Mepact) is an immunomodulator with antitumor effects that appear to be mediated via activation of monocytes and macrophages. After intravenous administration, mifamurtide is selectively phagocytosed by monocytes and macrophages. Cytosolic Mifamurtide specifically interacts with nucleotide-binding oligomerization domain 2 (NOD2) receptor that induces nuclear factor (NF)-kB activation and is implicated in innate immune defense. Activation of monocyte-mediated tumoricidal function was observed following in vivo treatment with mifamurtide in phase I/II clinical trials. Intravenous administration of mifamurtide inhibited tumor growth and increased survival in rodent models of lung and liver metastasis. In a large, randomized, open-label, multicenter, phase III trial, the addition of adjuvant (postoperative) mifamurtide to three- or four-drug combination chemotherapy (doxorubicin, cisplatin, and high-dose methotrexate with, or without, ifosfamide) was associated with a statistically significant improvement in overall survival in patients with newly diagnosed, high-grade, non-metastatic, resectable osteosarcoma. The pattern of outcome was generally similar in a small cohort of patients with metastatic disease who were enrolled in this trial. Mifamurtide is generally well tolerated; adverse events attributed to administration of the drug include chills, fever, headache, nausea, and myalgias. In the EU, mifamurtide is indicated in children, adolescents, and young adults for the treatment of high-grade, resectable, non-metastatic osteosarcoma after macroscopically complete surgical resection; it is administered by intravenous infusion in conjunction with postoperative multiagent chemotherapy. In the US, mifamurtide is currently an investigational agent that holds orphan drug status for the treatment of osteosarcoma.

Tilarginine is L-N-monomethyl arginine (L -NMMA), a non-selective inhibitor of nitric oxide synthase (NOS), which has been studied in the treatment of septic shock and cardiogenic shock complicating myocardial infarction. Despite strong evidence that excessive nitric oxide (NO) production plays a pivotal role in the pathogenesis of septic shock and may contribute to the pathogenesis of cardiogenic shock complicating myocardial infarction, outcome studies in these two disorders have proved disappointing. Tilarginine therapy was associated with an excess mortality, particularly at doses > 5 mg/(kg h), in septic shock, whereas the effects of a lower dose (1 mg/(kg h)) in cardiogenic shock complicating myocardial infarction were neutral. The excess mortality in patients with septic shock was almost certainly the result of unfavorable hemodynamic changes induced by Tilarginine (decreased cardiac output, increased pulmonary vascular resistance and reduced tissue oxygen delivery) whereas the lack of benefit in patients with cardiogenic shock complicating myocardial infarction may have been because the dose of Tilarginine was too low.

Vaniprevir (MK-7009) is an non-covalent competitive macrocyclic inhibitor of Hepatitis C virus NS3/4A protease genotype 1a and 1b proteases at subnanomolar concentrations with modestly shifted potency against genotype 2a and 2b proteases at low nanomolar concentrations. Merck & Co. developed vaniprevir in combination with standard therapy for the twice-daily treatment of hepatitis C virus infections. The product has been launched in Japan under name VANIHEP, and Merck reported in its 2014 annual report that the product will only be available in this region.

S-Adenosylmethionine (often referred to as SAMe) is a methyl donor and a cofactor for enzyme-catalyzed methylations, including catechol O-methyltransferase (COMT) and DNA methyltransferases (DNMT). Although present in all cells, it is concentrated in liver where 85% of all methylation reactions occur. SAM is anti-apoptotic in normal hepatocytes and normal colon epithelial cells but pro-apoptotic in liver human hepatocellular carcinoma (HCC), HepG2 cells and colon cancer cells. Because of structural instability, stable salt forms of SAM are required for its use as an oral drug. The commonly used salts: tosylate, butanedisulfonate, disulfate tosylate, disulfate ditosylate, and disulfate monotosylate. SAMe has been marketed in some European countries since the mid-1980s for the treatment of depression and for other medical conditions such as osteoarthritis (joint disease that causes joint pain and stiffness), fibromyalgia (widespread pain and stiffness). In addition, it is used to treat liver disease and migraine headaches. However, it is not formally approved in the UK for the treatment of depression, and in the USA, it is classified only as a dietary supplement. Some research suggests that it is more effective than placebo in treating mild-to-moderate depression and is just as effective as antidepressant medications without the side effects (headaches, sleeplessness, and sexual dysfunction). In addition, antidepressants tend to take 6 to 8 weeks to begin working, while It seems to begin more quickly. Researchers are not sure how SAMe works to relieve depression. But they speculate it might increase the amount of serotonin in the brain just as some antidepressants do. Many studies have examined injectable forms of SAMe, not oral supplements.

trans-Sobrerol is a mucolytic known due its emplyment in therapy for respiratory diseases. In preclinical studies sobrerol, administered daily at the oral dose of 400 mg/rat, markedly decreased the monocrotaline-induced alterations and regulate the development of pulmonary hypertension. Treatment with sobrerol was well tolerated and significantly reduced frontal headache and rhinorrhoea, efficacy being confirmed by rhinomanometry.

Oxyfedrine, an amino ketone derivative and partial agonist at beta receptors, has been shown to have potent antianginal properties and to increase coronary blood flow in normal and ischemic myocardial regions.

Imidapril (Tanatril), through its active metabolite imidaprilat, acts as an ACE inhibitor to suppress the conversion of angiotensin I to angiotensin II and thereby reduce total peripheral resistance and systemic blood pressure (BP). In clinical trials, oral imidapril was an effective antihypertensive agent in the treatment of mild to moderate essential hypertension. Some evidence suggests that imidapril also improves exercise capacity in patients with chronic heart failure (CHF) and reduces urinary albumin excretion rate in patients with type 1 diabetes mellitus. Imidapril was well tolerated, with a lower incidence of dry cough than enalapril or benazepril, and is a first choice ACE inhibitor for the treatment of mild to moderate essential hypertension.

Delapril is a lipophilic nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor, which has been shown to exert potent ACE inhibitory activity and is marketed as an antihypertensive drug. Delapril has been shown to exist in solution as a mixture of s-cis and s-trans conformational isomers, as a result of restricted rotation about the amide bond.

Tebipenem pivoxil is an oral carbapenem prodrug that was originated by Wyeth (now Pfizer). It was approved by Pharmaceuticals and Medical Devices Agency of Japan (PMDA) on Apr 22, 2009. It was developed and marketed as Orapenem® by Meiji Seika in Japan. Tebipenem pivoxil is a broad-spectrum orally-administered antibiotic, from the carbapenem subgroup of β-lactam antibiotics. Carbapenems are a class of beta-lactam antibiotics, which act by inhibiting the synthesis of the peptidoglycan layer of bacterial cell walls. It is used to treat otorhinolaryngological infection, otitis media and bacterial pneumonia. Orapenem® is available as granules for oral use, containing 100 mg Tebipenem pivoxil/g granules. According to the weight of children, 4 mg/kg, and twice a day after dinner.

Levormeloxifene (INN) is an experimental selective estrogen receptor modulator (SERM) that was being developed as an alternative to estrogen replacement therapy for the treatment and prevention of postmenopausal bone loss. Levormeloxifene is the levorotatory enantiomer of non-hormonal, non-steroidal oral contraceptive -- ormeloxifene (trade names Novex-DS, Centron, and Sevista). The development of Levormeloxifene was stopped because of a high incidence of gynecologic adverse events during clinical trials.