Asset Details
Do you wish to reserve the book?
Small molecule inhibition of cAMP response element binding protein in human acute myeloid leukemia cells
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Small molecule inhibition of cAMP response element binding protein in human acute myeloid leukemia cells
Do you wish to request the book?
Small molecule inhibition of cAMP response element binding protein in human acute myeloid leukemia cells
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Small molecule inhibition of cAMP response element binding protein in human acute myeloid leukemia cells
2016
Overview
The transcription factor CREB (cAMP Response-Element Binding Protein) is overexpressed in the majority of acute myeloid leukemia (AML) patients, and this is associated with a worse prognosis. Previous work revealed that CREB overexpression augmented AML cell growth, while CREB knockdown disrupted key AML cell functions
in vitro
. In contrast, CREB knockdown had no effect on long-term hematopoietic stem cell activity in mouse transduction/transplantation assays. Together, these studies position CREB as a promising drug target for AML. To test this concept, a small molecule inhibitor of CREB, XX-650-23, was developed. This molecule blocks a critical interaction between CREB and its required co-activator CBP (CREB Binding Protein), leading to disruption of CREB-driven gene expression. Inhibition of CBP–CREB interaction induced apoptosis and cell-cycle arrest in AML cells, and prolonged survival
in vivo
in mice injected with human AML cells. XX-650-23 had little toxicity on normal human hematopoietic cells and tissues in mice. To understand the mechanism of XX-650-23, we performed RNA-seq, ChIP-seq and Cytometry Time of Flight with human AML cells. Our results demonstrate that small molecule inhibition of CBP–CREB interaction mostly affects apoptotic, cell-cycle and survival pathways, which may represent a novel approach for AML therapy.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 38/39
/ 42/109
/ 59/5
/ 631/67
/ 96/100
/ Animals
/ Antineoplastic Agents - pharmacology
/ Cell Cycle Checkpoints - drug effects
/ CREB-Binding Protein - antagonists & inhibitors
/ CREB-Binding Protein - metabolism
/ Cyclic AMP response element-binding protein
/ Humans
/ Leukemia
/ Leukemia, Myeloid, Acute - drug therapy
/ Leukemia, Myeloid, Acute - mortality
/ Medicine
/ Mice
/ Oncology
/ Patients
/ Peptide Fragments - metabolism
/ Protein Binding - drug effects
/ Proteins
/ Sialoglycoproteins - metabolism
/ Survival
/ Toxicity
