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ERLOTINIB (OSI-420) –A SALT OF HCL

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:
1. Raymond, E.e.a., Epidermal growth factor receptor tyrosine kinase as a target for anticancer therapy. Drugs, 2000. 60(1): p. 41-42.
2. Moyer, J.D.e.a., Induction of Apoptosis and Cell Cycle Arrest by erlotinib, an Inhibitor of Epidermal Growth Factor Receptor Tyrosine Kinase. Cancer Res, 1997. 57: p. 4838-4848.
3. Yauch, R.L.e.a., Epithelial versus Mesenchymal Phenotype Determines in vitro Sensitivity and Predicts Clinical Activity of Erlotinib in Lung Cancer Patients. Clin Cancer Res, 2005. 11: p. 8686.
4. Herbst, R.S.e.a., A Phase III Trial of Erlotinib Hydrochloride (OSI-774) Combined With Carboplatin and Paclitaxel Chemotherapy in Advanced Non-Small-Cell Lung Cancer. Journal of Clinical Oncology, 2005. 23(25): p. 5892-5899.
5. Eberhard, D.A.e.a., Mutations in the Epidermal Growth Factor Receptor and in KRAS Are Predictive and Prognostic Indicators in Patients With Non-Small-Cell Lung Cancer Treated With Chemotherapy Alone and in Combination With Erlotinib. Journal of Clinical Oncology, 2005. 23(25): p. 5900-5909.
6. Buck, E.e.a., Rapamycin synergizes with the epidermal growth factor receptor inhibitor erlotinib in non-small-cell lung, pancreatic, colon, and breast tumors. Mol Cancer Ther, 2006. 5(11): p. 2676-84.
7. Tan, A.R.e.a., Evaluation of Biologic End Points and Pharmacokinetics in Patients With Metastatic Breast Cancer After Treatment With Erlotinib, an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor. Journal of Clinical Oncology, 2004. 22(15): p. 3080-3090.
8. Haas, D.A.e.a., Epidermal Growth Factor Receptor, Protein Kinase B/Akt, and Glioma Response to Erlotinib. J Natl Cancer Inst. 97(12): p. 880-887.
9. Starling, N.e.a., Role of Erlotinib in the management of pancreatic cancer. Ther Clin Risk Manag., 2006. 2(4): p. 435-445.
10. Moore, M.J.e.a., Erlotinib Plus Gemcitabine Compared With Gemcitabine Alone in Patients With Advanced Pancreatic Cancer: A Phase III Trial of the National Cancer Institute of Canada Clinical Trials Group. Journal of Clinical Oncology, 2007. 25(15): p. 1960-1966.
11. Rayes, B.F.e.a., Potentiation of the Effect of Erlotinib by Genistein in Pancreatic Cancer: The Role of Akt and Nuclear Factor-κB. Cancer Res, 2006. 66: p. 10553.
12. Lee, D.H.e.a., Phase II study of erlotinib as a salvage treatment for non-small-cell lung cancer patients after failure of gefitinib treatment. Annals of Oncology, 2008. 19(12): p. 2039-2042.
13. Philip, P.A.e.a., Phase II Study of Erlotinib (OSI-774) in Patients With Advanced Hepatocellular Cancer. Journal of Clinical Oncology, 2005. 23(27): p. 6657-6663.
14. Jackman, D.M.e.a., Phase II Clinical Trial of Chemotherapy-Naïve Patients ≥ 70 Years of Age Treated With Erlotinib for Advanced Non-Small-Cell Lung Cancer. Journal of Clinical Oncology, 2007  25(7): p. 760-766.
15. Bezjak, A., Symptom Improvement in Lung Cancer Patients Treated With Erlotinib: Quality of Life Analysis of the National Cancer Institute of Canada Clinical Trials Group Study BR.21. Journal of Clinical Oncology, 2006. 24(24): p. 3831-3837.
16. Clark, G.M.e.a., Smoking History and Epidermal Growth Factor Receptor Expression as Predictors of Survival Benefit from Erlotinib for Patients with Non-Small-Cell Lung Cancer in the National Cancer Institute of Canada Clinical Trials Group Study BR.21. Clinical Lung Cancer, 2006. 7(6): p. 389-394.
17. Cutsem, E.V.e.a., Phase III Trial of Bevacizumab in Combination With Gemcitabine and Erlotinib in Patients With Metastatic Pancreatic Cancer. Journal of Clinical Oncology, 2009. 27(13): p. 2231-2237.
18. Slamon, D.J.e.a., Use of Chemotherapy plus a Monoclonal Antibody against HER2 for Metastatic Breast Cancer That Overexpresses HER2. N Engl J Med, 2001. 344: p. 783-792.
19. Romond, E.H.e.a., Trastuzumab plus Adjuvant Chemotherapy for Operable HER2-Positive Breast Cancer. N Engl J Med, 2005. 353: p. 1673-1684.

 

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Cat.No. Product Name Information Publications Customer Product Validation
S2205 OSI-420 OSI-420 (DesMethyl Erlotinib, CP-473420) is the active metabolite of Erlotinib (EGFR inhibitor with IC50 of 2 nM). (14) (1)

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