Sandbox Reserved 1704

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== Applications ==
== Applications ==
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Anaplastic lymphoma kinase's involvement as a proto-oncogene in various types of cancers has made it a target for drug therapies for these types of cancers. One therapeutic medication that has been increasingly used with high levels of success is Crizotinib. This medication was approved by the FDA in January of 2021 for the treatment of pediatric/young adult ALK-positive anaplastic large cell lymphoma. The treatment has an overall response rate of 90%. Crizotinib works by binding to the ATP binding site of the kinase domain. Crizotinib binds preferentially to ATP in this region and therefore can effectively block the binding of ATP. With the binding of ATP being blocked, the intercellular signaling cascade cannot begin which works to prevent the cancer from growing and spreading.
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Anaplastic lymphoma kinase's involvement as a proto-oncogene in various types of cancers has made it a target for drug therapies for these types of cancers <ref name=”Lewis”>PMID:22734674</ref>. One therapeutic medication that has been increasingly used with high levels of success is Crizotinib. This medication was approved by the FDA in January of 2021 for the treatment of pediatric/young adult ALK-positive anaplastic large cell lymphoma. The treatment has an overall response rate of 90%. Crizotinib works by binding to the ATP binding site of the kinase domain <ref name=”Sahu”>PMID:24455567</ref>. Crizotinib binds preferentially to ATP in this region and therefore can effectively block the binding of ATP <ref name=”Sahu”/>. With the binding of ATP being blocked, the intercellular signaling cascade cannot begin which works to prevent the cancer from growing and spreading <ref name=”Sahu”/>.

Revision as of 14:29, 15 March 2022

This Sandbox is Reserved from February 28 through September 1, 2022 for use in the course CH462 Biochemistry II taught by R. Jeremy Johnson at the Butler University, Indianapolis, USA. This reservation includes Sandbox Reserved 1700 through Sandbox Reserved 1729.
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Contents

Anaplastic Lymphoma Kinase (ALK)

Introduction

Anaplastic lymphoma kinase is a receptor tyrosine kinase (RTK) that is important in regulating functions within the central nervous system [1]. The route to the discovery of the structure of this protein was rather complex, spanning almost 20 years with the kinase domain being discovered in 1994, the full protein structure in 1997, and the ligand structures discovered in 2014. These structures were found using cryo-electron microscopy,nuclear magnetic resonance, and X-ray crystallography. Anaplastic lymphoma kinase is a proto-oncogene with mutations associated with various types of cancers, including non-small-cell lung cancer, anaplastic large cell lymphoma, squamous cell carcinoma, and inflammatory myofibroblastic cancer.

General Structure

Structure Specifics

Applications

Anaplastic lymphoma kinase's involvement as a proto-oncogene in various types of cancers has made it a target for drug therapies for these types of cancers [2]. One therapeutic medication that has been increasingly used with high levels of success is Crizotinib. This medication was approved by the FDA in January of 2021 for the treatment of pediatric/young adult ALK-positive anaplastic large cell lymphoma. The treatment has an overall response rate of 90%. Crizotinib works by binding to the ATP binding site of the kinase domain [3]. Crizotinib binds preferentially to ATP in this region and therefore can effectively block the binding of ATP Cite error: Invalid <ref> tag; refs with no content must have a name. With the binding of ATP being blocked, the intercellular signaling cascade cannot begin which works to prevent the cancer from growing and spreading Cite error: Invalid <ref> tag; refs with no content must have a name.


References

  1. ↑ Reshetnyak AV, Rossi P, Myasnikov AG, Sowaileh M, Mohanty J, Nourse A, Miller DJ, Lax I, Schlessinger J, Kalodimos CG. Mechanism for the activation of the anaplastic lymphoma kinase receptor. Nature. 2021 Dec;600(7887):153-157. doi: 10.1038/s41586-021-04140-8. Epub 2021, Nov 24. PMID:34819673 doi:http://dx.doi.org/10.1038/s41586-021-04140-8
  2. ↑ Lewis RT, Bode CM, Choquette D, Potashman M, Romero K, Stellwagen JC, Teffera Y, Moore E, Whittington DA, Chen H, Epstein LF, Emkey R, Andrews PS, Yu V, Saffran DC, Xu M, Drew AE, Merkel P, Szilvassy S, Brake RL. The discovery and optimization of a novel class of potent, selective and orally bioavailable Anaplastic Lymphoma Kinase (ALK) Inhibitors with potential utility for the treatment of cancer. J Med Chem. 2012 Jun 26. PMID:22734674 doi:10.1021/jm3005866
  3. ↑ Sahu A, Prabhash K, Noronha V, Joshi A, Desai S. Crizotinib: A comprehensive review. South Asian J Cancer. 2013 Apr;2(2):91-7. doi: 10.4103/2278-330X.110506. PMID:24455567 doi:http://dx.doi.org/10.4103/2278-330X.110506
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