9z1l: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older edit
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,331,615 edits
No edit summary
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,331,615 edits
No edit summary
 
Line 1: Line 1:
'''Unreleased structure'''


The entry 9z1l is ON HOLD  until Paper Publication
==Structure of KIT V654A mutant with Compound 1==
<StructureSection load='9z1l' size='340' side='right'caption='[[9z1l]], [[Resolution|resolution]] 1.54&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9z1l]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9Z1L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9Z1L FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.543&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1CZZ:~{N}2-methyl-~{N}4-[5-(1-methylpyrazol-4-yl)-4-propan-2-yloxy-pyridin-2-yl]pyrimidine-2,4-diamine'>A1CZZ</scene>, <scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9z1l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9z1l OCA], [https://pdbe.org/9z1l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9z1l RCSB], [https://www.ebi.ac.uk/pdbsum/9z1l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9z1l ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Gastrointestinal stromal tumor (GIST) is the most common type of sarcoma of the gastrointestinal tract, with approximately 5000 new cases annually in the USA. Approximately 80% of GIST cases are driven by activating mutations in KIT in exon 9 or 11. Resistance to present therapies like imatinib often arises from secondary KIT mutations, especially V654A (exon 13), which is the most frequent resistance mutation. Tyrosine kinase inhibitors (TKIs) currently approved for GIST can cause dose-limiting side effects due to off-target inhibition of other kinases. Herein, we report the discovery and optimization of BLU-654 (compound 18), a highly potent and kinome-sparing KIT V654A inhibitor. Preclinical efficacy studies demonstrated its prolonged antitumor activity in a KIT V654A cell-derived xenograft mouse model. BLU-654 offers a potent and selective profile suitable for combination therapy for KIT-mutant GIST patients.


Authors: Kim, J.L.
Design and Synthesis of BLU-654, a Potent and Selective Mutant KIT V654A Inhibitor for the Treatment of Imatinib-Resistant GIST.,Moine L, Hu W, Davis A, Perola E, Guo J, Barvian K, Choi YS, Grassian A, Kim JL, Ahmad OK, Dineen TA J Med Chem. 2026 Mar 10. doi: 10.1021/acs.jmedchem.5c03554. PMID:41807293<ref>PMID:41807293</ref>


Description: Structure of KIT V654A mutant with Compound 1
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Kim, J.L]]
<div class="pdbe-citations 9z1l" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Kim JL]]
Retrieved from "https://proteopedia.org/9z1l"