Brivanib is a pyrrolotriazine-based compound and an inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) with potential antineoplastic activity. It specifically targets and strongly binds to human VEGFR-2, a tyrosine kinase receptor and pro-angiogenic growth factor expressed almost exclusively on vascular endothelial cells. Blockade of VEGFR-2 by this agent may lead to an inhibition of VEGF-stimulated endothelial cell migration and proliferation, thereby inhibiting tumor angiogenesis. Brivanib has a moderate potency compared to VEGFR-2 against VEGFR-1 and FGFR-1 as well. Brivanib is suggested to be efficient in treatment of hepatocellular carcinoma (HCC). As first-line and as second-line therapy brivanib demonstrated promising antitumor activity and a manageable safety profile in patients with advanced, unresectable HCC in phase II clinical trials. On 3 march 2011, orphan designation was granted by the European Commission to Bristol-Myers Squibb for brivanib alaninate for the treatment of hepatocellular carcinoma.[

Torcetrapib is a CETP inhibitor which was developed by Pfizer for the treatment of diseases associated with elevated level of cholesterol. The drug was tested in phase III (in combination with atorvastatin) of clinical trials in coronary heart disease patients as well as in patients with hyperlipoproteinemia, hypertriglyceridemia, hypercholesterolemia, hyperlipidemia, however its development was terminated due to the high risk of death and heart problems.

Rabusertib is a Chk1 kinase inhibitor which was developed by ICOS for the treatment of cancer. The drug was tested in phase II of clinical trials for pancreatic cancer and non small cell lung carcinoma, but its development was discontinued. Now the drug is undergoing phase I trial in Japanese patients with solid tumors.

Sanguinarine is an extract of the bloodroot plant Sanguinaria canadensis, a member of the poppy family. It is an inhibitor of protein phosphatases PP1, PP2C and PP2B in vitro. Also inhibits mitogen-activated protein kinase phosphatase-1 (MKP-1) and other enzymes. Sanguinarine exerts a protective effect in cerebral ischemia, and this effect is associated with its anti-inflammatory and anti-apoptotic properties. It was clinically tested as an agent against gingivitis and tooth plaques.

AMG-487 is a potent and selective orally bioavailable chemokine (C-X-C motif) receptor 3 (CXCR3) antagonist that displays dose- and time-dependent pharmacokinetics in human subjects after multiple oral dosing. AMG-487 is an 8-azaquinazolinone, it can prevent the chemokines I-IP-10 and I-ITAC from binding to CXCR3. The preclinical properties of AMG487 has been extensively studied. The compound displays a greater than 1000-fold selectivity for CXCR3 versus a panel of other receptors, including 11 chemokine receptors. The safety profile of AMG487, as assessed by various genotoxicity and cardiotoxicity assays, revealed no major concerns. The ability of AMG487 to inhibit inflammatory cell migration in vivo was confirmed in a mouse model of bleomycin-induced cellular recruitment, where AMG487 significantly reduced infiltration of macrophages and lymphocytes into the lungs in CXCR3-KO mice. In a mouse model for idiopathic pneumonia syndrome (IPS), AMG487 reduced recruitment of donor T cells to the lung after allogeneic stem cell transplantation, leading to improved survival rates. Likewise, reductions in inflammation, pannus formation, and cartilage damage were observed upon administering AMG487. The preclinical studies convincingly paved the way for clinical studies on two inflammation-related diseases: psoriasis and rheumatoid arthritis. In 2003, results of a Phase I trial on AMG487 were disclosed. The compound was assessed for safety and pharmacokinetics in 30 healthy males in a randomised, double blind, placebo-controlled dose-escalation study. Generally, the compound was well tolerated and adverse events were mild to moderate. Disappointingly, no significant differences in the endpoints (psoriasis severity index or physician global assessment scores) were seen between patient groups. AMG-487 progressed to Phase II clinical trials but has been withdrawn because of lack of efficacy.

Mobocertinib (EXKIVITY™) is a first-in-class EGFR tyrosine kinase inhibitor being developed for the treatment of EGFR exon 20 insertion (EGFRex20ins) -positive non-small cell lung cancer (NSCLC). Mobocertinib is a kinase inhibitor of the epidermal growth factor receptor (EGFR) that irreversibly binds to and inhibits EGFR exon 20 insertion mutations at lower concentrations than wild type (WT) EGFR. Two pharmacologically-active metabolites (AP32960 and AP32914) with similar inhibitory profiles to mobocertinib have been identified in the plasma after oral administration of mobocertinib. In vitro, mobocertinib also inhibited the activity of other EGFR family members (HER2 and HER4) and one additional kinase (BLK) at clinically relevant concentrations (IC50 values <2 nM). Based on efficacy in patients whose disease had progressed on or after platinum-based therapy in a phase I/II trial, mobocertinib was recently granted accelerated approval in the USA in this indication. The drug is also being assessed for marketing approval in various other countries and territories including the EU and China.

Rifamycin SV is a derivative of antibiotic rifamycin B (the natural fermentation product of S. mediterranei broths). The primary target of rifampicin on whole bacteria is the synthesis of RNA. Rifamycin belongs to the ansamycin class of antibacterial drugs and acts by inhibiting the beta subunit of the bacterial DNA-dependent RNA polymerase, blocking one of the steps in DNA transcription. This results in inhibition of bacterial synthesis and consequently growth of bacteria. Rifampicin exhibits bactericidal activity on Gram-positive and Gram-negative bacteria and on mycobacteria. Rifamycin SV MMX® (AEMCOLO), a non-absorbable rifamycin antibiotic formulated using the multi-matrix system, was designed to exhibit its pharmacological action on the distal small intestine and colon. AEMCOLO is indicated for the treatment of travelers’ diarrhea (TD) caused by non-invasive strains of Escherichia coli in adults.

Indacaterol is an ultra-long-acting beta-adrenoceptor agonist developed by Novartis. It was approved by the European Medicines Agency (EMA) under the trade name Onbrez Breezhaler on November 30, 2009, and by the United States Food and Drug Administration (FDA), under the trade name Arcapta Neohaler, on July 1, 2011. It needs to be taken only once a day, unlike the related drugs formoterol and salmeterol. It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD) (long-term data in patients with asthma are thus far lacking). It is delivered as an aerosol formulation through a dry powder inhaler.

Retapamulin is a topical antibiotic which was approved by FDA (Altabax brand name) for the treatment of impetigo due to Staphylococcus aureus (methicillin-susceptible isolates only) or Streptococcus pyogenes. Retapamulin exerts its antibacterial action by binding to 50S subunit of the bacterial ribosome.

Subitramine is a potent inhibitor of monoamines (serotonin, dopamine, noradrenaline) reuptake that was approved by FDA for the treatmen of obesity. Sibutramine is metabolized to metabolites M1 and M2 which are more active toward the monoamine transporters.The drug was withdrawn from the market because of clinical trial data indicating an increased risk of heart attack and stroke. It was sold under a variety of brand names including Reductil, Meridia and Sibutrex.