4. You develop the covalently-acting irreversible kinase inhibitor ibrutinib shown on the left that reacts potently with a cysteine in the ATP binding pocket of the cancer-promoting kinase Bruton's Tyrosin Kinase (BTK). You would like to know whether ibrutinib engages and selectively targets BTK in vivo in the tumor of a mouse model of cancer. Describe experimentally how you would use activity-based protein profiling to assess whether ibrutinib inhibited BTK in vivo in the tumor and also determine how selectively ibrutinib engaged BTK compared to other kinases in the tumor? ( NH, H₂N- N ibrutinib OH OH OH OH activity-based probe for kinases that covalently modifies active-site lysine of all kinase ATP binding pocket W ta t C

4. You develop the covalently-acting irreversible kinase inhibitor ibrutinib shown on the left that reacts potently with a cysteine in the ATP binding pocket of the cancer-promoting kinase Bruton's Tyrosin Kinase (BTK). You would like to know whether ibrutinib engages and selectively targets BTK in vivo in the tumor of a mouse model of cancer. Describe experimentally how you would use activity-based protein profiling to assess whether ibrutinib inhibited BTK in vivo in the tumor and also determine how selectively ibrutinib engaged BTK compared to other kinases in the tumor? ( NH, H₂N- N ibrutinib OH OH OH OH activity-based probe for kinases that covalently modifies active-site lysine of all kinase ATP binding pocket W ta t C

Biology (MindTap Course List)

11th Edition

ISBN:9781337392938

Author:Eldra Solomon, Charles Martin, Diana W. Martin, Linda R. Berg

Publisher:Eldra Solomon, Charles Martin, Diana W. Martin, Linda R. Berg

Chapter6: Cell Communication

Section: Chapter Questions

Problem 16TYU

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