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ERLOTINIB (OSI-420) –A SALT OF HCL

by Selleckchem | May 01 2012

INTRODUCTION:
Erlotinib drug is commonly known as HCl salt. It is also called as OSI-420 EGFR inhibitor. It is a small molecule of tyrosine kinase inhibitor that works against the receptor for epidermal growth factor. This epidermal growth factor results usually very high levels of expression and mostly gets mutated in case of various types of tumors, hence a valuable and attractive target for anti-tumor therapy [1]. One can order OSI-420 to any of the supplier OSI-420. So one can purchase OSI-420 by paying Erlotinib price to its supplier that is around $65 for 1000 mg vial. Erlotinib structure describes that it has 2 rings of quinazoline. OSI-420 has found to be inhibiting the autophosphorylation of epidermal growth factor to render downstreaming of already stopped signaling cascade by binding to ATP binding site of EGFR in the reversible manner leading to a permanat change in its conformation or structure. Erlotinib solubility is 18 mg/ml in DMSO while it is very poorly soluble in water and ethanol. To inhibit EGFR tyrosine kinase enzyme in human, Erlotinib IC50 was found to be almost 20 nM [2]. OSI-420 EGFR inhibitor must be kept far away from different oxidizing agents so that it will remain stable and safe.

ERLOTINIB: PANCREATIC, BREAST AND LUNG CANCER
Erlotinib is an orally administered drug and a reversible epidermal growth factor inhibiting molecule. It was tested against various types of tumors like pancreatic, lung and breast cancer and it was found to exhibiting very remarkable results. An in vitro study of Erlotinib against lung cancer patients in pre-clinical and clinical trials reveals that this drug is quite suitable and less toxic in the cellular systems [3]. OSI-420 EGFR inhibitor was used alone and also in combination with Rapamycin or some other chemotherapeutic agents for lung cancer [4-6] and with these chemical agents it exhibited good and synergistic results also showing higher efficiency and no resistance development regarding breast, colon, pancreatic and lung cancers [6]. A detail dose of Erlotinib was also assessed in case of breast tumors according to the drug’s toxicity profile, pharmacokinetic properties and clearance rate [7] and also further used for the treatment of gliomas [8]. Effects of Erlotinib were also tested against EGFR pathway [8] and was also tested Erlotinib alone and in combination with Gemcitabine against pancreatic cancer [9-10]. According to another research the involvement of Akt and NF-kB cascades was also observed as a mechanism of OSI-420 to stimulate the repression in pancreatic cancer [11] hence threw a new light on mode of activity of OSI-420 and explored a new horizon of its therapeutic potential.

ERLOTINIB IN CLINICAL TRIALS
For its successful results in clinical trials of phase II against pancreatic, breast and lung cancers OSI-420 Desmethyl Erlotinib has proved itself very valuable medicine for their treatment. Erlotinib was also proved very remarkable against small cell lung carcinoma after the failure of Gefitinib [12] as cancer cells are known to have potential of adapting evasion strategies for ongoing therapeutic field hence shifted the paradigm from Gefitinib to Erlotinib triggered apoptosis in Gefitinib-resistant cell lines. Regarding pancreatic cancer, a clinical trial of phase II, Erlotinib promised better results and in case of advanced metastatic hepatocellular carcinoma caused its regression [13]. This drug has also found to exhibit good tolerance in clinical trials phase II of patients of elder lung cancer [14] as those patients were complaining about secondary complications generated by side effects of induction of drug. In OSI-420 lung cancer patients under phase III clinical trials, it has been reported that the there was an overall improvement of survival, side effects and low toxicity levels along with the regression in the volume of tumor. OSI-420 has experienced very remarkable success when used against patients lung cancer patients who have a known smoking history [16]. This medicine has also been used for pancreatic cancer patients under clinical trials phase 3 [17] and also as a combinational therapeutic tool in case of breast tumors [18-19] so now it is a great therapeutic horizon for above all three types of cancers.

REFERENCES:
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