ALK
Dec 05 2012
The significance of transition from preclinical to clinical studies has been recognized leading to the re-organization of research units into ALK Inhibitors translational groups bringing involved disciplines closer together. The intent is to leverage basic science to better support the translation of in vitro and in vivo preclinical data into clinical decisions
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Oct 30 2012
Inhibition of KSP affects the formation of the bipolar spindle for the separation and purification of chromosomes w During mitosis. This chromosome abnormality leads to programmed cell death in mitotic cells. Here we have shown that SB715992 cell death induced apoptosis significantly PC 3 prostate cancer cells
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Mar 20 2012
ALK (ANAPLASTIC LYMPHOMA KINASE) RECEPTOR:
Anaplastic lymphoma kinase or ALK is encoded by ALK gene and it is also called as CD246 (Cluster of Differentiation-246). This kinase is famous for the brain development but by the genetic fusion of any other gene it can be an oncogenic gene, another reason for its genetic variability is due to the normally found mutations of DNA. In case of ALCLs or large cell lymphomas, NPM (nucleophosmin) is present in fusion form with ALK and this is responsible for the 60% of this cancer. In some of the other cancers like NSCLC (non-small cell lung cancer) and most of adenocarcinomas, the ALK-EML4 fused genes are found as the main cause of tumor formation. Similarly in a pediatric cancer that is known as neuroblastoma, mutated ALK is reported as the main reason in various studies. All of these important examples enlighten the significance of this pathway in different cancers and tumors therefore the discovery or development of such compounds which inhibit the ALK TKs pathway is important. Certain approved inhibitors like Crizotinib used for lung cancer treatment enhances the uses of different inhibitors found in inhibitor library including SB-431542 ALK inhibitor.
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Mar 13 2012
Introduction: Inhibitors of ALK
Activin receptor like-kinases (ALK1) are defined as being a type 1 receptor specifically for the transforming growth factor ß (TGF-ß) family of proteins. It is recorded that ALK1 expression is found in blood vessels and may be linked to vascular formation. Since tumor growth is dependant on generating a vascular skeleton to support itself ALK1 appears to be a potential target for chemotherapeutic action. Analysis of hereditary hemorrhagic telangiectasia disorders revealed a mutation n the ALK1 gene transcription. ALK is encoded by ALK gene and plays an important role in the development of brain function. Fusion of the ALK gene with other genes such as the nucleophosmin gene or the EML4 gene is can be linked to specifc types of carcinomas. In NSCLC the EML4- ALK fusion is theroised to be the driving force behind the tumor. Inhibition of the ALK, therefore presents itself forward a potential target for chemotherapy. This is confirmed by the EML4-ALK inhibitor Crizotinib which has achieved approval for use in NSCLC patients. Potentially SB-431542 is another small molecule which could make a huge impact since the SB-431542 IC50 has been determined to be 94nM for ALK5, it remains to be determined whether this can be translated into a sucessfuly chemotherapy agent.
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Aug 19 2011
This article reviews the ALK pathway and the Clinical–Translational Advances of different ALK inhibitors.
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Jul 19 2011
This review which was published in Nature Reviews Cancer concludes the pathways which ALK is involved in and targets that ALK is related to. The content also includes ALK as a therapeutic target in cancer.
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