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INTRODUCTION Cancers show large scale of heterogenicity and account for a huge death toll. A normal functioning of different signaling pathways is very essential for the proper functioning of the cells. Amongst these pathways, the Ras activated MAPK pathway, is very important and its hyperactivation leads to cancer. Mutations within the Ras gene like K-ras mutations are the primary cause behind the majority of cancers. Tipifarnib adopts a novel mechanism to control this mutation. ROLE OF TIPIFARNIB IN CONTROLLING PANCREATIC CANCER Pancreatic cancer rate has increased enormously and it is generally cured with the help of chemoradiotherapy or gemcitabine based treatment. Especially to check the process of metastasis, gemcitabine has been found to be the only solution. Tipifarnib is a new inhibitor which performs a unique function of inhibiting FPT (farnesyl protein transferase) enzyme. A number of intracellular proteins like Ras protein have a CAAX-box in the C-terminal region and contain cysteine residues. FPT enzyme catalyses the transfer of farnesyl isoprenoid (consisting 15 carbon atoms) part to the cysteine residues. Ras proteins get anchored to the membrane in the presence of FTP enzyme and this farnesylation step is very critical. Around 90% cases of pancreatic cancers are associated with the K-ras mutations which stimulates the constitutive activation of the Ras oncoproteins. Hence if FTP action is inhibited, the K-ras mutation can also be controlled. Tipifarnib showed significant antiproliferative effects in large number of cancer cases. It inhibited the growth of the cancer cells at the concentration ranging between 9.5 – 500 nmol/L. A combination of Tipifarnib with gemcitabine was found to be more efficient in curing this kind of cancer. This combination was safe and did not project any adverse effects under physiological conditions [1]. TIPIFARNIB- EFFICIENTLY INHIBITS MYELOGENOUS LEUKEMIA Tipifarnib acts as an angiogenesis inhibitors in many pancreatic cancer cases [1]. The cause behind the occurrence of myeloid malignancies is different and cannot be generally cured with the help of normal cytotoxic drugs. Tipifarnib was studied under phase II clinical trials. When it was administered alone, patients suffering from secondary AML or those showing adverse cytogenetics, were benefited after the treatment [2]. PROAPOPTOTIC ACTIVITY OF IFN-? ENHANCED AFTER THE TREATMENT WITH TIPIFARNIB IFN-? stimulates EGFR which later activates the Ras dependent MAPK pathway. This pathway ultimately promotes survival and inhibits the process of apoptosis. When IFNalpha was administered in combination with Tipifarnib the process of proliferation was inhibited and apoptosis was promoted. The activation of Ras and Eek1/2 after IFNalpha induction, was completely reversed by this combination of IFNalpha with Tipifarnib. It also reduced the activity of Akt and delayed the growth of tumors. The immunoconjugate formation between Raf-1/bcl-2 was enhanced. The antitumor activity of IFNalpha is efficiently potentiated by Tipifarnib, under in vitro and in vivo conditions [3]. GENETIC PATHWAYS MODULATED BY TIPIFARNIB After thorough screening of the compound library of farnesyltransferase inhibitors, Tipifarnib was obtained. It alters a number of genetic pathways in case of myeloid leukemia (acute cases). The genes which are involved in the process of cell signaling, immunity, organization of the cytoskeletal parts are all affected by Tipifarnib inhibitor [4]. CONCLUSION In summary, Tipifarnib is a unique enzyme which acts on the FTP enzyme and regulates the MAPK pathway. REFERENCES 1. Cutsem EV, Velde HV, et al. Phase III Trial of Gemcitabine Plus Tipifarnib Compared With Gemcitabine Plus Placebo in Advanced Pancreatic Cancer. JCO 2001 April 15; 22(8):1430-1438. 2. Karp JE, Smith BD, et al. Phase II Trial of Tipifarnib as Maintenance Therapy in First Complete Remission in Adults with Acute Myelogenous Leukemia and Poor-Risk Features. Clin Cancer Res 2008 May 15; 14; 3077. 3. Caraglia M, Marra M, et al. The farnesyltransferase inhibitor R115777 (ZARNESTRA) enhances the pro-apoptotic activity of interferon-alpha through the inhibition of multiple survival pathways. Int J Cancer 2007 Nov 15; 121(10): 2317-30. 4. Raponi M, Belly RT, et al. Microarray analysis reveals genetic pathways modulated by tipifarnib in acute myeloid leukemia. BMC Cancer 2004; 4:56. Related Posts: SP600125 – A JNK INHIBITOR GDC-0879 – TARGETS B-RAF AND CONTROLS A VARIETY OF CANCERS Related to TIPIFARNIB – INHIBITS FTP ENZYME TIPIFARNIB – INHIBITS THE PATHWAYS WHICH INVOLVE ISOPRENYLATED PROTEINS INTRODUCTION Cytokines stimulate the process of apoptosis within the cancerous cells. Cytokines act through the MAPK pathway. Hence when hyperactivation of MAPK pathway takes place ... TIPIFARNIB (ZARNESTRA) – REGULATES FARNESYLATION INTRODUCTION Tipifarnib is alternatively known as R115777 and is marketed with the trade name Zarnestra. It inhibits the farnesyltransferase enzyme. It acts on the Ras ... SP600125 – AN INHIBITOR WITH ANTHRAPYRAZOLONE RING INTRODUCTION Inflammatory diseases are associated with an increase in immune proteins which make the pathology of the disease irreversible. Some transcription factors stimulate multiple genes ... We pays great attention to the purity, stability and activity of the products like Doxorubicin, Fingolimod, Adriamycin & more. Not only could we provides the chemical test data, such as HNMR, LC-MS and HPLC, but also provides the reviews overall evaluations of the products from the customers who have used our products. Western Blot, MTT, RT-PCR, ICH photos or figures provide a double guarantee for the biological activities of our products in life-science research.
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