Aliskiren – the only direct renin inhibitor which is clinically used as an antihypertensive drug. Aliskiren is the first of a new class of antihypertensive agents. Aliskiren is a new renin inhibitor of a novel structural class that has recently been shown to be efficacious in hypertensive patients after once-daily oral dosing. In short-term studies, it was effective in lowering blood pressure either alone or in combination with valsartan and hydrochlorothiazide, and had a low incidence of serious adverse effects. It was approved by the Food and Drug Administration in 2007 for the use as a monotherapy or in combination with other antihypertensives. Aliskiren is marketed under the trade name Tekturna. Aliskiren effectively reduces functional plasma renin activity by binding to renin with high affinity, preventing it from converting angiotensinogen to angiotensin I. The inhibition of renin by aliskiren is associated with a reduction in circulating levels of angiotensin I and II, with a resultant increase in plasma renin concentration and inhibit activation of mitogen-activated protein kinases ERK1 (p44) and ERK2 (p42).

Temsirolimus is an intravenous drug for the treatment of renal cell carcinoma (RCC), developed by Wyeth Pharmaceuticals and approved by the FDA in late May 2007, and was also approved by the European Medicines Agency (EMEA) on November 2007. It is a derivative of sirolimus and is sold as Torisel. Temsirolimus is an inhibitor of mTOR (mammalian target of rapamycin). Temsirolimus binds to an intracellular protein (FKBP-12), and the protein-drug complex inhibits the activity of mTOR that controls cell division. Inhibition of mTOR activity resulted in a G1 growth arrest in treated tumor cells. When mTOR was inhibited, its ability to phosphorylate p70S6k and S6 ribosomal protein, which are downstream of mTOR in the PI3 kinase/AKT pathway was blocked. In in vitro studies using renal cell carcinoma cell lines, temsirolimus inhibited the activity of mTOR and resulted in reduced levels of the hypoxia-inducible factors HIF-1 and HIF-2 alpha, and the vascular endothelial growth factor.

Decitabine was first synthesized by Pliml and Sorm in the Institute of Organic Chemistry, Czechoslovak Academy of Sciences in 1964. Later, the drug was approved by FDA for the treatment of myelodysplastic syndromes in patients with cancer. Upon administration the decitabine is metabolized to the active phosphorylated metabolite which is incorporated into DNA and thus inhibits DNA methyltransferase (decitabine deplete DNMT1).

Sunitinib (marketed as Sutent by Pfizer, and previously known as SU11248) is an oral, small-molecule, multi-targeted receptor tyrosine kinase inhibitor that was approved by the FDA for the treatment of renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor. Sunitinib was evaluated for its inhibitory activity against a variety of kinases and was identified as an inhibitor of platelet-derived growth factor receptors (PDGFRa and PDGFRb), vascular endothelial growth factor receptors (VEGFR1, VEGFR2, and VEGFR3), stem cell factor receptor (KIT), Fms-like tyrosine kinase-3 (FLT3), colony-stimulating factor receptor Type 1 (CSF-1R), and the glial cell-line derived neurotrophic factor receptor (RET). Sunitinib adverse events are considered somewhat manageable and the incidence of serious adverse events low. The most common adverse events associated with sunitinib therapy are fatigue, diarrhea, nausea, anorexia, hypertension, yellow skin discoloration, hand-foot skin reaction, and stomatitis. In the placebo-controlled Phase III GIST study, adverse events which occurred more often with sunitinib than placebo included diarrhea, anorexia, skin discoloration, mucositis/stomatitis, asthenia, altered taste, and constipation. Dose reductions were required in 50% of the patients studied in RCC in order to manage the significant toxicities of this agent.

Deferasirox (marketed as Exjade, Desirox, Deferasirox) is an iron chelator. Its main use is to reduce chronic iron overload in patients who are receiving long term blood transfusions for conditions such as beta-thalassemia and other chronic anemias. It is the first oral medication approved for this purpose in the USA by FDA in November 2005. It is approved in the European Union by the European Medicines Agency (EMA) for children 6 years and older for chronic iron overload from repeated blood transfusions. Deferasirox is highly selective for iron as Fe3+. In approximately 1-year clinical trials of patients with transfusional chronic iron overload associated with beta-thalassaemia, sickle cell disease, myelodysplastic syndrome or other rare chronic anaemias, deferasiroxhad a beneficial effect on liver iron concentrations (LIC) and serum ferritin levels. Deferasirox can cause acute renal failure, fatal in some patients and requiring dialysis in others. It was showed that most fatalities occurred in patients with multiple comorbidities in advanced stages of their hematological disorders.

Sorafenib (BAY 43-9006), marketed as Nexavar by Bayer, is a drug approved for the treatment of advanced renal cell carcinoma (primary kidney cancer, hepatocellular carcinoma and for the treatment of patients with locally recurrent or metastatic, progressive, differentiated thyroid carcinoma (DTC) that is refractory to radioactive iodine treatment. It has also received "Fast Track" designation by the FDA for the treatment of advanced hepatocellular carcinoma (primary liver cancer), and has since performed well in Phase III trials. Sorafenib was shown to interact with multiple intracellular (CRAF, BRAF and mutant BRAF) and cell surface kinases (KIT, FLT- 3, VEGFR- 2, VEGFR- 3, and PDGFR- ß). Several of these kinases are thought to be involved in angiogenesis. Thus, sorafenib may inhibit tumor growth by a dual mechanism, acting either directly on the tumor (through inhibition of Raf and Kit signaling) and/or on tumor angiogenesis (through inhibition of VEGFR and PDGFR signaling). Sorafenib inhibited tumor growth of the murine renal cell carcinoma, RENCA, and several other human tumor xenografts in athymic mice. A reduction in tumor angiogenesis was seen in some tumor xenograft models.

Tipranavir (PNU-140690, trade mark APTIVUS) is a potent, orally bioavailable nonpeptidic HIV protease inhibitor of the 5,6-dihydro-4-hydroxy-2-pyrone sulfonamide class. Tipranavir has potent in vitro activity against a variety of HIV-1 laboratory strains and clinical isolates, including those resistant to ritonavir, as well as HIV-2. The drug is launched in several countries, including the US and in the EU. APTIVUS, co-administered with ritonavir, is indicated for combination antiretroviral treatment of HIV-1 infected patients who are treatment-experienced and infected with HIV-1 strains resistant to more than one protease inhibitor.

Lenalidomide (trade name Revlimid) is a derivative of thalidomide introduced in 2004. It is an immunomodulatory agent with anti-angiogenic properties. Revlimid in combination with dexamethasone is indicated for the treatment of patients with multiple myeloma (MM) who have received at least one prior therapy. Also is indicated for the treatment of patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities. In addition, Revlimid is indicated for the treatment of patients with mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib. The mechanism of action of lenalidomide remains to be fully characterized. Lenalidomide inhibited the secretion of pro-inflammatory cytokines and increased the secretion of anti-inflammatory cytokines from peripheral blood mononuclear cells. Lenalidomide causes a delay in tumor growth in some in vivo nonclinical hematopoietic tumor models including multiple myeloma. Immunomodulatory properties of lenalidomide include activation of T cells and natural killer (NK) cells, increased numbers of NKT cells, and inhibition of pro-inflammatory cytokines (e.g., TNF-α and IL-6) by monocytes. In multiple myeloma cells, the combination of lenalidomide and dexamethasone synergizes the inhibition of cell proliferation and the induction of apoptosis. Recently was discovered, that protein cereblon (CRBN) is a proximate, therapeutically important molecular target of lenalidomide. Low CRBN expression was found to correlate with drug resistance in multiple myeloma (MM) cell lines and primary MM cells. One of the downstream targets of CRBN identified is interferon regulatory factor 4 (IRF4), which is critical for myeloma cell survival and is down-regulated by (immune-modulatory drugs) treatment. CRBN is also implicated in several effects of immunomodulatory drugs, such as down-regulation of tumor necrosis factor-α (TNF-α) and T cell immunomodulatory activity, demonstrating that the pleotropic actions of the immunomodulatory drugs (IMiDs) are initiated by binding to CRBN. Future dissection of CRBN downstream signaling will help to delineate the underlying mechanisms for IMiD action and eventually lead to development of new drugs with more specific anti-myeloma activities. It may also provide a biomarker to predict IMiD response and resistance. Lenalidomide also inhibited the expression of cyclooxygenase-2 (COX-2) but not COX-1 in vitro.

Arranon is a nucleoside metabolic inhibitor indicated for the treatment of patients with T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma. It is a purine nucleoside analog converted to its corresponding arabinosylguanine nucleotide triphosphate (araGTP), resulting in inhibition of DNA synthesis and cytotoxicity. Administration of nelarabine in combination with adenosine deaminase inhibitors, such 195 as pentostatin, is not recommended. The most common (≥20%) adverse reactions were: anemia, thrombocytopenia, neutropenia, nausea, diarrhea, vomiting, constipation, fatigue, pyrexia, cough, and dyspnea

Erlotinib hydrochloride (trade name Tarceva, Genentech/OSIP, originally coded as OSI-774) is a drug used to treat non-small cell lung cancer, pancreatic cancer and several other types of cancer. Similar to gefitinib, erlotinib specifically targets the epidermal growth factor receptor (EGFR) tyrosine kinase. It binds in a reversible fashion to the adenosine triphosphate (ATP) binding site of the receptor. Erlotinib has recently been shown to be a potent inhibitor of JAK2V617F activity. JAK2V617F is a mutant of tyrosine kinase JAK2, is found in most patients with polycythemia vera (PV) and a substantial proportion of patients with idiopathic myelofibrosis or essential thrombocythemia. The study suggests that erlotinib may be used for treatment of JAK2V617F-positive PV and other myeloproliferative disorders. The mechanism of clinical antitumor action of erlotinib is not fully characterized. Erlotinib inhibits the intracellular phosphorylation of tyrosine kinase associated with the epidermal growth factor receptor (EGFR). Specificity of inhibition with regard to other tyrosine kinase receptors has not been fully characterized. EGFR is expressed on the cell surface of normal cells and cancer cells.