View source for 9odr


==Structure of CRBN TBD bound to compound C1==
<StructureSection load='9odr' size='340' side='right'caption='[[9odr]], [[Resolution|resolution]] 2.42&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9odr]] is a 4 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=9ODR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9ODR 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]] 2.42&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1CAV:(3~{S})-3-(6-oxidanylidenespiro[2,8-dihydrofuro[2,3-e]isoindole-3,4-piperidine]-7-yl)piperidine-2,6-dione'>A1CAV</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=9odr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9odr OCA], [https://pdbe.org/9odr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9odr RCSB], [https://www.ebi.ac.uk/pdbsum/9odr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9odr ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/CRBN_HUMAN CRBN_HUMAN] Autosomal recessive nonsyndromic intellectual deficit;Distal monosomy 3p. The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/CRBN_HUMAN CRBN_HUMAN] Component of some DCX (DDB1-CUL4-X-box) E3 protein ligase complex, a complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins and is required for limb outgrowth and expression of the fibroblast growth factor FGF8. In the complex, may act as a substrate receptor. Regulates the assembly and neuronal surface expression of large-conductance calcium-activated potassium channels in brain regions involved in memory and learning via its interaction with KCNT1.<ref>PMID:18414909</ref> <ref>PMID:20223979</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Estrogen receptor alpha (ERalpha) is a key therapeutic target in ER+/HER2- breast cancer, but ESR1 mutations drive resistance to endocrine therapies. Heterobifunctional degraders (HBDs) targeting ERalpha offer a promising strategy to overcome this resistance. Here, we report PVTX-321 (16a), a potent ER HBD derived from a novel spirocyclic cereblon ligand and an ERalpha binder. PVTX-321 achieves a DC(50) of 0.15 nM in MCF-7 cells and acts as a strong antagonist (IC(50) = 59 nM), suppressing proliferation in ERalpha+ cell lines, including mutant variants (Y537S, D538G). It demonstrates favorable oral bioavailability, dose-dependent ERalpha degradation in vivo and induces tumor regression at 10 mg/kg (QD) in MCF-7 xenografts. With minimal CYP inhibition and a strong preclinical safety profile, PVTX-321 is a promising candidate for advancing ER+/HER2- breast cancer treatment.

Discovery and Characterization of PVTX-321 as a Potent and Orally Bioavailable Estrogen Receptor Degrader for ER+/HER2- Breast Cancer.,Xu G, Havens CG, Deng Q, Lowenstein C, Samanta D, Vidal B, Behshad E, Russell M, Orth P, Rice CT, Nagilla R, Kirchhoff P, Chen Z, Rej RK, Acharyya RK, Wu D, Wang S, Zhang W, Wu W, Jolivette L, Strickland C, Sui Z, Mohammad HP, Zhang X, Priestley ES J Med Chem. 2025 May 14. doi: 10.1021/acs.jmedchem.5c00223. PMID:40366756<ref>PMID:40366756</ref>

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