9sp9: Difference between revisions

Line 1:

~~'''Unreleased structure'''~~

~~The entry~~ 9sp9 is ~~ON HOLD until Paper~~ Publication

==Human DDR1 in complex with a indoline inhibitor==

== Structural highlights ==

<table><tr><td colspan='2'>[[9sp9]] 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=9SP9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9SP9 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]] 2.59Å</td></tr>

<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1JPO:~{N}-(1-imidazo[1,2-a]pyridin-3-ylcarbonyl-2,3-dihydroindol-6-yl)-3-[(4-methylpiperazin-1-yl)methyl]-5-(trifluoromethyl)benzamide'>A1JPO</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=9sp9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9sp9 OCA], [https://pdbe.org/9sp9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9sp9 RCSB], [https://www.ebi.ac.uk/pdbsum/9sp9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9sp9 ProSAT]</span></td></tr>

</table>

== Function ==

[https://www.uniprot.org/uniprot/DDR1_HUMAN DDR1_HUMAN]

== Publication Abstract from PubMed ==

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease, with excessive Extracellular Matrix (ECM) deposition impairing gas exchange, leading to lung failure. Current treatments are limited, with lung transplantation as the only cure. Discoidin Domain Receptors (DDR1/2), collagen-activated receptor tyrosine kinases, orchestrate collagen deposition in fibrotic diseases. We report the discovery and optimization of novel DDR1/2 kinase-domain inhibitors suitable for inhaled administration. Starting from a benzylamine scaffold, three chemical series, namely indolines, pyrrolidines, and azetidines, were explored. The first two showed potent DDR1 inhibition and lung retention but faced safety and selectivity challenges. The azetidine compound 37 was identified as the most promising one for its nanomolar potency, improved kinase selectivity, reduced cardiotoxicity risk, and excellent inhaled PK profile. It demonstrated activity in a collagen-induced pharmacodynamic mouse model, supporting its potential as an inhaled DDR inhibitor for IPF and validating the azetidine scaffold as a promising starting point for further optimization.

~~Authors~~: Rizzi, A., Giuliani, M.

A Journey through Scaffolds: Indolines, Pyrrolidines, and Azetidines in the Quest for Inhaled DDR Inhibitors for IPF.,Carzaniga L, Rancati F, Rizzi A, Mazzucato R, Iotti N, Ghidini E, Bertolini S, Bignami F, Fioni A, Mileo V, Vaccaro F, Murgo A, Freire Bento A, Capelli AM, Whittaker BP, Levanto S, Chapman RSL, Hamasova Z, Hardy CJ, Clark DE, Allen R, Briggs MA, Hann E, Lee S, Matthews C, Todd D, Hawkins J, Giuliani M J Med Chem. 2026 Mar 26;69(6):6610-6633. doi: 10.1021/acs.jmedchem.5c02830. Epub , 2026 Feb 20. PMID:41715301<ref>PMID:41715301</ref>

~~Description~~: ~~Human DDR1 in complex with a indoline inhibitor~~

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

[[Category: ~~Unreleased~~ Structures]]

</div>

[[Category: Giuliani, M]]

[[Category: Rizzi, A]]

== References ==

__TOC__

</StructureSection>

[[Category: Homo sapiens]]

[[Category: Large Structures]]

[[Category: Giuliani M]]

[[Category: Rizzi A]]

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9sp9 is ON HOLD  until Paper Publication
+==Human DDR1 in complex with a indoline inhibitor==
+<StructureSection load='9sp9' size='340' side='right'caption='[[9sp9]], [[Resolution|resolution]] 2.59&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9sp9]] 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=9SP9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9SP9 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]] 2.59&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1JPO:~{N}-(1-imidazo[1,2-a]pyridin-3-ylcarbonyl-2,3-dihydroindol-6-yl)-3-[(4-methylpiperazin-1-yl)methyl]-5-(trifluoromethyl)benzamide'>A1JPO</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=9sp9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9sp9 OCA], [https://pdbe.org/9sp9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9sp9 RCSB], [https://www.ebi.ac.uk/pdbsum/9sp9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9sp9 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/DDR1_HUMAN DDR1_HUMAN]
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease, with excessive Extracellular Matrix (ECM) deposition impairing gas exchange, leading to lung failure. Current treatments are limited, with lung transplantation as the only cure. Discoidin Domain Receptors (DDR1/2), collagen-activated receptor tyrosine kinases, orchestrate collagen deposition in fibrotic diseases. We report the discovery and optimization of novel DDR1/2 kinase-domain inhibitors suitable for inhaled administration. Starting from a benzylamine scaffold, three chemical series, namely indolines, pyrrolidines, and azetidines, were explored. The first two showed potent DDR1 inhibition and lung retention but faced safety and selectivity challenges. The azetidine compound 37 was identified as the most promising one for its nanomolar potency, improved kinase selectivity, reduced cardiotoxicity risk, and excellent inhaled PK profile. It demonstrated activity in a collagen-induced pharmacodynamic mouse model, supporting its potential as an inhaled DDR inhibitor for IPF and validating the azetidine scaffold as a promising starting point for further optimization.
-Authors: Rizzi, A., Giuliani, M.
+A Journey through Scaffolds: Indolines, Pyrrolidines, and Azetidines in the Quest for Inhaled DDR Inhibitors for IPF.,Carzaniga L, Rancati F, Rizzi A, Mazzucato R, Iotti N, Ghidini E, Bertolini S, Bignami F, Fioni A, Mileo V, Vaccaro F, Murgo A, Freire Bento A, Capelli AM, Whittaker BP, Levanto S, Chapman RSL, Hamasova Z, Hardy CJ, Clark DE, Allen R, Briggs MA, Hann E, Lee S, Matthews C, Todd D, Hawkins J, Giuliani M J Med Chem. 2026 Mar 26;69(6):6610-6633. doi: 10.1021/acs.jmedchem.5c02830. Epub , 2026 Feb 20. PMID:41715301<ref>PMID:41715301</ref>
-Description: Human DDR1 in complex with a indoline inhibitor
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Giuliani, M]]
+<div class="pdbe-citations 9sp9" style="background-color:#fffaf0;"></div>
-[[Category: Rizzi, A]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Giuliani M]]
+[[Category: Rizzi A]]