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ERLOTINIB (OSI-420) – AN HCL SALT

by Selleckchem | Apr 02 2012

INTRODUCTION:
Erlotinib is commonly known as Erlotinib salt of HCl. It is a very small tyrosine kinase inhibitor molecule, works against the epidermal growth factor receptor. This EGFR usually gives high level of expression and most often gets mutated in different types of cancers, hence an attractive target for the anti-cancer therapy [1]. Researchers can purchase Erlotinib from supplier Erlotinib which sale it under the trading name of Tarceva. By paying Erlotinib prices around $65 for a 1000 mg vial one can buy OSI-420. Structure of Erlotinib reveals that it is having 2 rings of quinazoline. Erlotinib has found to inhibit the autophosphorylation of EGFR to render the downstreaming of stopped signaling pathway by binding to the ATP binding region of EGFR in a reversible manner causing a permanent conformational change in its structure. Erlotinib is poorly soluble in ethanol and water but gives a solution of 18 mg/ml upon heating in DMSO. For the inhibition of EGFR tyrosine kinase in human, Erlotinib IC50 is found to be near 20 nM [2]. Erlotinib must be stored far away from oxidizing agents to keep it safe and stable.

ERLOTINIB: BREAST, LUNG AND PANCREATIC CARCINOMA
Erlotinib as an oral and reversible EGFR inhibitor molecule was tested against different types of cancers like lung, pancreatic and breast cancer and it has exhibited very remarkable results there. According to an in vitro analysis of Erlotinib in case of clinical and preclinical trials of patients of lung carcinoma, it has proved itself quite suitable and minimum toxic in cellular system [3]. Erlotinib EGFR inhibitor was applied either alone or combined with Rapamycin or any other chemotherapeutic agent for lung carcinoma [4-6] and along with these agents it showed very good and synergistic results including high efficiency and lack of resistance development in case of lung, colon, breast and pancreatic cancers [6]. Erlotinib detailing dose according to its phamacokinetics, its toxicty profile and clearance rate were also assesed in breast carcinoma [7] and was further used for gliomas treatment [8]. Its effects on EGFR cascade were tested [8] and it was also tested alone and combined with Gemcitabine against pancreatic tumors [9-10]. Another study revealed the involvement of NF-B and Akt pathways as mechanism of Erlotinib to stimulate the regression in pancreatic carcinoma [11] hence throwing a new light on mode of action of Erlotinib and exploring a new avenue for its therapeutic potential.

ERLOTINIB: CLINICAL TRIALS
Due to its successful role in phase II clinical studies against breast, pancreatic and lung cancers, OSI-420 Desmethyl Erlotinib has become a valuable drug for their treatment. After the failure of treatment by Gefitinib, Erlotinib was proved very successful against small cell lung carcinoma [12] as tumor cells are usually known to adapt evasion strategies for the ongoing therapeutic field hence shifting of paradigm from the Gefitinib to Erlotonib stimulated apoptotic cell death in cells resistant for Gefitinib. A phase 2 clinical trial of Erlotinib pancreatic cancer promised good results in case of patients of advanced metastatic hepatocellular carcinoma by stopping its progression [13]. Erlotinib was also found to have a good tolerance in elder lung cancer patients under phase 2 clinical trials [14] who were complaining of secondary complications produced by the side effects of induced medication. Erlotinib lung cancer clinical trial phase III has reported the improved overall survival and less toxicity level and side effects along the regression in tumor volume. Erlotinib has experienced valuable success in case of using against the patients of lung cancer having known smoking background [16]. Erlotinib has been also used in the phase III clinical studies of pancreatic cancers [17] and as a combinational therapy in case of breast cancer [18-19] hence now a great therapeutic regime for these all three cancers.

REFERENCES:
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