View source for 9uzt


==Crystal structure of human PTPN2 with inhibitor K-38==
<StructureSection load='9uzt' size='340' side='right'caption='[[9uzt]], [[Resolution|resolution]] 2.17&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9uzt]] 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=9UZT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9UZT 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]] 2.17&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1EQR:~{N}-cycloheptyl-4-[3-fluoranyl-5-oxidanyl-4-[1,1,4-tris(oxidanylidene)-1,2,5-thiadiazolidin-2-yl]phenyl]-1~{H}-imidazole-2-carboxamide'>A1EQR</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=9uzt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9uzt OCA], [https://pdbe.org/9uzt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9uzt RCSB], [https://www.ebi.ac.uk/pdbsum/9uzt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9uzt ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PTN2_HUMAN PTN2_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Melanoma is a highly aggressive skin cancer with strong metastatic potential, posing significant clinical challenges. Currently, melanoma treatment commonly includes chemotherapy and immunotherapy; nevertheless, the treatment modalities have specific limitations. PTPN2 (protein tyrosine phosphatase nonreceptor type 2) has emerged as a promising therapeutic target. Through rational drug design, we identified compound K-38, a potent PTPN2 inhibitor (IC(50) = 7.05 nM) with high safety (hERG IC(50) &gt; 40 muM) and excellent liver metabolic stability (T(1/2) = 408 min). Compound K-38 also showed improved oral bioavailability (F = 10.46%) over AC-484 (F = 1.40%) (Zheng European Journal of Medicinal Chemistry 2024, 270, 116390, ). In vivo, compound K-38 significantly suppressed melanoma growth, especially when combined with anti-PD-1 therapy, outperforming AC-484. It enhanced lymphocyte infiltration into tumors and modulated IFN-gamma signaling pathways. These findings indicate that compound K-38 is a potent small molecule inhibitor of PTPN2, laying the groundwork for the future development of PTPN2-targeted therapeutics.

Targeting Protein Tyrosine Phosphatase Nonreceptor Type 2 with a Novel Inhibitor for the Treatment of Melanoma.,Kuang W, Li Q, Wang W, Wang D, Tong C, Song M, Han K, Liu J, Chen A, Chen Y, Wang L, Hao H, Wang X, Xiao Y, Yang P J Med Chem. 2025 Nov 27;68(22):24649-24671. doi: 10.1021/acs.jmedchem.5c02622. , Epub 2025 Nov 8. PMID:41204903<ref>PMID:41204903</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9uzt" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Tong C]]