OCA at 08:31, 19 December 2018

OCA — Wed, 19 Dec 2018 08:31:41 GMT

←Older revision		Revision as of 08:31, 19 December 2018
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-	'''Unreleased structure'''

-	~~The entry~~ 6i4b is ~~ON HOLD~~	+	==Plasmodium falciparum dihydroorotate dehydrogenase (DHODH) co-crystallized with 3-Hydroxy-1-methyl-5-((3-(trifluoromethyl)phenoxy)methyl)-1H-pyrazole-4-carboxylic acid==
		+	<StructureSection load='6i4b' size='340' side='right' caption='[[6i4b]], [[Resolution\|resolution]] 1.98Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6i4b]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I4B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6I4B FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=E2N:1-methyl-3-oxidanyl-5-[[3-(trifluoromethyl)phenoxy]methyl]pyrazole-4-carboxylic+acid'>E2N</scene>, <scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=ORO:OROTIC+ACID'>ORO</scene></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6i4b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i4b OCA], [http://pdbe.org/6i4b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6i4b RCSB], [http://www.ebi.ac.uk/pdbsum/6i4b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6i4b ProSAT]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) has been clinically validated as a target for antimalarial drug discovery, as a triazolopyrimidine class inhibitor (DSM265) is currently undergoing clinical development. Here, we have identified new hydroxyazole scaffold-based PfDHODH inhibitors belonging to two different chemical series. The first series was designed by a scaffold hopping strategy that exploits the use of hydroxylated azoles. Within this series, the hydroxythiadiazole 3 was identified as the best selective PfDHODH inhibitor (IC50 12.0muM). The second series was designed by modulating four different positions of the hydroxypyrazole scaffold. In particular, hydroxypyrazoles 7e and 7f were shown to be active in the low muM range (IC50 2.8 and 5.3muM, respectively). All three compounds, 3, 7e and 7f showed clear selectivity over human DHODH (IC50>200muM), low cytotoxicity, and retained micromolar activity in P. falciparum-infected erythrocytes. The crystallographic structures of PfDHODH in complex with compounds 3 and 7e proved their binding mode, supplying essential data for future optimization of these scaffolds.

-	~~Authors~~:	+	Hydroxyazole scaffold-based Plasmodium falciparum dihydroorotate dehydrogenase inhibitors: Synthesis, biological evaluation and X-ray structural studies.,Pippione AC, Sainas S, Goyal P, Fritzson I, Cassiano GC, Giraudo A, Giorgis M, Tavella TA, Bagnati R, Rolando B, Caing-Carlsson R, Costa FTM, Andrade CH, Al-Karadaghi S, Boschi D, Friemann R, Lolli ML Eur J Med Chem. 2018 Nov 22;163:266-280. doi: 10.1016/j.ejmech.2018.11.044. PMID:30529545<ref>PMID:30529545</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 6i4b" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Al-Kadaraghi, S]]
		+	[[Category: Boschi, D]]
		+	[[Category: Goyal, P]]
		+	[[Category: Pippione, A C]]
		+	[[Category: Sainas, S]]
		+	[[Category: Dhodh]]
		+	[[Category: Oxidoreductase]]
		+	[[Category: Plasmodium falciparum dhodh]]

OCA: Protected "6i4b" [edit=sysop:move=sysop]

OCA — Wed, 14 Nov 2018 06:25:20 GMT

Protected "6i4b" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:25, 14 November 2018

OCA: New page: '''Unreleased structure''' The entry 6i4b is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 14 Nov 2018 06:25:19 GMT

New page: '''Unreleased structure''' The entry 6i4b is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6i4b is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

6i4b - Revision history

OCA at 08:31, 19 December 2018

OCA: Protected "6i4b" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 6i4b is ON HOLD Authors: Description: Category: Unreleased Structures