The drug is getting evaluated for prostate and glioblastoma multiforme cancer sufferers in phase ? and ? trials and for various types of cancer in preclinical phases. Leflunomide is additionally getting applied for therapy of rheumatoid arthritis. In Table 3, an overview is given of single targeted and multi targeted PDGFR tyrosine kinase inhibitors in different phases of development. CDK inhibition Quite a few multi kinase inhibitors which are in development target the VEGFR family members as well as the PDGFR fam ily. The rationale behind that is that tumor survival, growth and metastasis depend on tumor cell proliferation and angiogenesis, the final of that is mediated by endothelial cell proliferation. Targeting these processes simultaneously by blocking RTKs on tumor cells and VEGF action on endothelial cells may be appropriate in cancer therapy.

Semax inib inhibits the tyrosine kinase receptors VEGFR 2, c KIT and FLT 3. The inhibitor showed good results Dopamine-β-Hydroxylase activity in phase ? AML trials. However, no goal response charges have been obtained in other forms of cancer. A additional se lective angiogenesis inhibitor is vatalanib, which inhibits VEGFR1, 2 and 3. At larger concentrations the receptors PDGFR? and c Kit may also be inhibited. Clinical studies in several sorts of cancer have already been concluded. The in hibitor sunitinib targets a number of kinase receptors like VEGFR, PDGFR, c KIT, and FLT 3, thereby resulting in the two direct antitumor likewise as antiangiogenic activity. It is actually approved for progressed GIST following imatinib therapy, for intolerated imatinib treatment for GIST and for advanced renal cell carcinoma.

One more authorized tyrosine kinase inhibitor for advanced renal Gene expression cell carcinoma is sorafenib, which targets both proliferation and angiogenesis by inhib iting c KIT and Flt 3 to the one hand and VEGFR and PDGFR about the other. In addition, it inhibits the serine/ threonine RAF/MEK/ERK pathway. Phase ? trials had been carried out in NSCLC by which the drug showed reasonable activity with sickness stabilization as well as the drug is in development for numerous other types of cancer. Its activity is especially promising in hepatocellular carcinoma. The mixture of sorafenib and erlotinib showed a superb response and sickness stabilization in NSCLC even in patients with K ras mutations, using a median time to progression of ten mo, which is considered for being on account of simultaneous inhibition of numerous signaling pathways, such because the Ras pathway.

The blend was additive to synergistic in NSCLC cells, together with the most pronounced effect found in cells with mu tant K ras. This combination is also becoming evaluated in hepatocellular carcinoma for which sorafenib is additionally regis tered. In Table 4, an overview potent AMPK activator is given of both authorized tyrosine kinase inhibitors and tyrosine kinase inhibitors in development that are targeted against both the PDGFR and the VEGFR tyrosine kinase families. The considerations to determine regardless of whether multiple single kinase inhibitors or possibly a single multi kinase inhibitor is pref erable in cancer treatment are according to aspects concerning efficacy, resistance, pharmacokinetics, selectivity and tu mor atmosphere.