6s6w: Difference between revisions

Latest revision as of 06:25, 1 October 2025

Crystal Structure of human ALDH1A3 in complex with 2,6-diphenylimidazo[1,2-a]pyridine (compound GA11) and NAD+

Structural highlights

Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.25Å
Ligands:	GOL, KXT, NAD
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

Glioblastoma multiforme (GBM) is the deadliest form of brain tumor. It is known for its ability to escape the therapeutic options available to date thanks to the presence of a subset of cells endowed with stem-like properties and ability to resist to cytotoxic treatments. As the cytosolic enzyme aldehyde dehydrogenase 1A3 turns out to be overexpressed in these kinds of cells, playing a key role for their vitality, treatments targeting this enzyme may represent a successful strategy to fight GBM. In this work, we describe a novel class of imidazo[1,2-a]pyridine derivatives as aldehyde dehydrogenase 1A3 inhibitors, reporting the evidence of their significance as novel drug candidates for the treatment of GBM. Besides showing an interesting functional profile, in terms of activity against the target enzyme and selectivity toward highly homologous isoenzymes, representative examples of the series also showed a nanomolar to picomolar efficacy against patient-derived GBM stem-like cells, thus proving the concept that targeting aldehyde dehydrogenase might represent a novel and promising way to combat GBM by striking its ability to divide immortally.

Imidazo[1,2-a]pyridine Derivatives as Aldehyde Dehydrogenase Inhibitors: Novel Chemotypes to Target Glioblastoma Stem Cells.,Quattrini L, Gelardi ELM, Coviello V, Sartini S, Ferraris DM, Mori M, Nakano I, Garavaglia S, La Motta C J Med Chem. 2020 Apr 20. doi: 10.1021/acs.jmedchem.9b01910. PMID:32223240^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Quattrini L, Gelardi ELM, Coviello V, Sartini S, Ferraris DM, Mori M, Nakano I, Garavaglia S, La Motta C. Imidazo[1,2-a]pyridine Derivatives as Aldehyde Dehydrogenase Inhibitors: Novel Chemotypes to Target Glioblastoma Stem Cells. J Med Chem. 2020 Apr 20. doi: 10.1021/acs.jmedchem.9b01910. PMID:32223240 doi:https://dx.doi.org/10.1021/acs.jmedchem.9b01910

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OCA

[1] Quattrini L, Gelardi ELM, Coviello V, Sartini S, Ferraris DM, Mori M, Nakano I, Garavaglia S, La Motta C. Imidazo[1,2-a]pyridine Derivatives as Aldehyde Dehydrogenase Inhibitors: Novel Chemotypes to Target Glioblastoma Stem Cells. J Med Chem. 2020 Apr 20. doi: 10.1021/acs.jmedchem.9b01910. PMID:32223240 doi:https://dx.doi.org/10.1021/acs.jmedchem.9b01910

[1]

@@ Line 3: / Line 3: @@
 <StructureSection load='6s6w' size='340' side='right'caption='[[6s6w]], [[Resolution|resolution]] 3.25&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6s6w]] is a 2 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=6S6W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6S6W FirstGlance]. <br>
+<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6S6W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6S6W 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]] 3.25&#8491;</td></tr>
 <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=KXT:2,6-diphenylimidazo[1,2-a]pyridine'>KXT</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</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=6s6w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6s6w OCA], [https://pdbe.org/6s6w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6s6w RCSB], [https://www.ebi.ac.uk/pdbsum/6s6w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6s6w ProSAT]</span></td></tr>
 </table>
-== Disease ==
-[https://www.uniprot.org/uniprot/AL1A3_HUMAN AL1A3_HUMAN] Isolated anophthalmia - microphthalmia. The disease is caused by mutations affecting the gene represented in this entry.
-== Function ==
-[https://www.uniprot.org/uniprot/AL1A3_HUMAN AL1A3_HUMAN] Recognizes as substrates free retinal and cellular retinol-binding protein-bound retinal. Seems to be the key enzyme in the formation of an RA gradient along the dorso-ventral axis during the early eye development and also in the development of the olfactory system (By similarity).
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 28: / Line 24: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
 [[Category: Large Structures]]
 [[Category: Ferraris DM]]

6s6w: Difference between revisions

Latest revision as of 06:25, 1 October 2025

Crystal Structure of human ALDH1A3 in complex with 2,6-diphenylimidazo[1,2-a]pyridine (compound GA11) and NAD+

Structural highlights

Publication Abstract from PubMed

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References

Contents

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