A PHP Error was encountered

Severity: Warning

Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests

Filename: helpers/my_audit_helper.php

Line Number: 143

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 143
Function: file_get_contents

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 209
Function: simplexml_load_file_from_url

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 994
Function: getPubMedXML

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3134
Function: GetPubMedArticleOutput_2016

File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global

File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword

File: /var/www/html/index.php
Line: 316
Function: require_once

Correspondence on "Synergy and Antagonism between Allosteric and Active-Site Inhibitors of Abl Tyrosine Kinase". | LitMetric

AI Article Synopsis

  • Soellner’s research reveals that ATP-competitive inhibitors of ABL kinase bind differently than allosteric inhibitors like asciminib, which cannot bind to ABL at the same time as ATP-competitive drugs.
  • Our own studies, however, indicate that combining asciminib with other ATP-competitive inhibitors like imatinib, nilotinib, or dasatinib results in additive effects rather than synergy or antagonism on BCR-ABL-dependent cell growth.
  • Additionally, advanced techniques show that asciminib can form complexes with ATP-competitive inhibitors, suggesting potential benefits for patients with chronic myeloid leukemia.

Article Abstract

Soellner published on the interplay between allosteric and adenosine triphosphate (ATP)-competitive inhibitors of ABL kinase, showing that the latter preferably binds to different conformational states of ABL compared to allosteric agents that specifically target the ABL myristate pocket (STAMP) and deducing that asciminib cannot bind to ABL simultaneously with ATP-competitive drugs. These results are to some extent in line with ours, although our analyses of dose-response matrices from combinations of asciminib with imatinib, nilotinib or dasatinib, show neither synergy nor antagonism, but suggest additive antiproliferative effects on BCR-ABL-dependent KCL22 cells. Furthermore, our X-ray crystallographic, solution nuclear magnetic resonance (NMR), and isothermal titration calorimetry studies show that asciminib can bind ABL concomitantly with type-1 or -2 ATP-competitive inhibitors to form ternary complexes. Concomitant binding of asciminib with imatinib, nilotinib, or dasatinib might translate to benefit some chronic myeloid leukaemia patients.

Download full-text PDF

Source
http://dx.doi.org/10.1002/anie.202117276DOI Listing

Publication Analysis

Top Keywords

inhibitors abl
8
atp-competitive inhibitors
8
asciminib bind
8
bind abl
8
asciminib imatinib
8
imatinib nilotinib
8
nilotinib dasatinib
8
abl
6
correspondence "synergy
4
"synergy antagonism
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!