OCA at 06:56, 11 October 2023

2023-10-11T06:56:09Z

←Older revision		Revision as of 06:56, 11 October 2023
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	==Selective inhibition of carbonic anhydrase IX activity, using compound SLC-149, displays limited anticancer effects in breast cancer cell lines==		==Selective inhibition of carbonic anhydrase IX activity, using compound SLC-149, displays limited anticancer effects in breast cancer cell lines==
-	<StructureSection load='6nm0' size='340' side='right'caption='[[6nm0]]' scene=''>	+	<StructureSection load='6nm0' size='340' side='right'caption='[[6nm0]], [[Resolution\|resolution]] 1.44Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NM0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NM0 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6nm0]] 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=6NM0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NM0 FirstGlance]. <br>
-	</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=6nm0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nm0 OCA], [https://pdbe.org/6nm0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nm0 RCSB], [https://www.ebi.ac.uk/pdbsum/6nm0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nm0 ProSAT]</span></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.44Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=KRY:4-[3-(2,4-difluorophenyl)-2-oxo-2,3-dihydro-1H-imidazol-1-yl]benzene-1-sulfonamide'>KRY</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=6nm0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nm0 OCA], [https://pdbe.org/6nm0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nm0 RCSB], [https://www.ebi.ac.uk/pdbsum/6nm0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nm0 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/CAH2_HUMAN CAH2_HUMAN] Defects in CA2 are the cause of osteopetrosis autosomal recessive type 3 (OPTB3) [MIM:[https://omim.org/entry/259730 259730]; also known as osteopetrosis with renal tubular acidosis, carbonic anhydrase II deficiency syndrome, Guibaud-Vainsel syndrome or marble brain disease. Osteopetrosis is a rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. The disorder occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Autosomal recessive osteopetrosis is usually associated with normal or elevated amount of non-functional osteoclasts. OPTB3 is associated with renal tubular acidosis, cerebral calcification (marble brain disease) and in some cases with mental retardation.<ref>PMID:1928091</ref> <ref>PMID:1542674</ref> <ref>PMID:8834238</ref> <ref>PMID:9143915</ref> <ref>PMID:15300855</ref>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/CAH2_HUMAN CAH2_HUMAN] Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion into the anterior chamber of the eye.<ref>PMID:10550681</ref> <ref>PMID:11831900</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Carbonic anhydrase IX (CAIX) is considered a target for therapeutic intervention in solid tumors. In this study, the efficacy of the inhibitor, 4-(3-(2,4-difluorophenyl)-oxoimidazolidin-1-yl)benzenesulfonamide (SLC-149), is evaluated on CAIX and a CAIX-mimic. We show that SLC-149 is a better inhibitor than acetazolamide against CAIX. Binding of SLC-149 thermally stabilizes CAIX-mimic at lower concentrations compared to that of CAII. Structural examinations of SLC-149 bound to CAIX-mimic and CAII explain binding preferences. In cell culture, SLC-149 is a more effective inhibitor of CAIX activity in a triple-negative breast cancer cell line than previously studied sulfonamide inhibitors. SLC-149 is also a better inhibitor of activity in cells expressing CAIX versus CAXII. However, SLC-149 has little effect on cytotoxicity, and high concentrations are required to inhibit cell growth, migration, and invasion. These data support the hypothesis that CAIX activity, shown to be important in regulating extracellular pH, does not underlie its ability to control cell growth.
		+
		+	Inhibition of Carbonic Anhydrase Using SLC-149: Support for a Noncatalytic Function of CAIX in Breast Cancer.,Mboge MY, Combs J, Singh S, Andring J, Wolff A, Tu C, Zhang Z, McKenna R, Frost SC J Med Chem. 2021 Feb 11;64(3):1713-1724. doi: 10.1021/acs.jmedchem.0c02077. Epub , 2021 Feb 1. PMID:33523653<ref>PMID:33523653</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6nm0" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Carbonic anhydrase 3D structures\|Carbonic anhydrase 3D structures]]		*[[Carbonic anhydrase 3D structures\|Carbonic anhydrase 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: McKenna R]]		[[Category: McKenna R]]
	[[Category: Singh S]]		[[Category: Singh S]]

OCA at 09:04, 21 July 2021

2021-07-21T09:04:17Z

←Older revision		Revision as of 09:04, 21 July 2021
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-	'''Unreleased structure'''

-	~~The entry~~ 6nm0 is ~~ON HOLD until Paper Publication~~	+	==Selective inhibition of carbonic anhydrase IX activity, using compound SLC-149, displays limited anticancer effects in breast cancer cell lines==
		+	<StructureSection load='6nm0' size='340' side='right'caption='[[6nm0]]' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NM0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NM0 FirstGlance]. <br>
		+	</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=6nm0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nm0 OCA], [https://pdbe.org/6nm0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nm0 RCSB], [https://www.ebi.ac.uk/pdbsum/6nm0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nm0 ProSAT]</span></td></tr>
		+	</table>

-	~~Authors: Singh, S., McKenna, R.~~	+	==See Also==
-		+	*[[Carbonic anhydrase 3D structures\|Carbonic anhydrase 3D structures]]
-	~~Description: Selective inhibition of carbonic~~ anhydrase ~~IX activity, using compound SLC-149, displays limited anticancer effects in breast cancer cell lines~~	+	__TOC__
-	[[Category: ~~Unreleased~~ Structures]]	+	</StructureSection>
-	[[Category: ~~Mckenna,~~ R]]	+	[[Category: Large Structures]]
-	[[Category: Singh, S]]	+	[[Category: McKenna R]]
		+	[[Category: Singh S]]

OCA at 13:42, 27 February 2019

2019-02-27T13:42:08Z

←Older revision		Revision as of 13:42, 27 February 2019
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6nm0 is ON HOLD	+	The entry 6nm0 is ON HOLD until Paper Publication

	Authors: Singh, S., McKenna, R.		Authors: Singh, S., McKenna, R.

OCA: Protected "6nm0" [edit=sysop:move=sysop]

2019-01-16T10:45:33Z

Protected "6nm0" [edit=sysop:move=sysop]

←Older revision

Revision as of 10:45, 16 January 2019

OCA: New page: '''Unreleased structure''' The entry 6nm0 is ON HOLD Authors: Singh, S., McKenna, R. Description: Selective inhibition of carbonic anhydrase IX activity, using compound SLC-149, displa...

2019-01-16T10:45:32Z

New page: '''Unreleased structure''' The entry 6nm0 is ON HOLD Authors: Singh, S., McKenna, R. Description: Selective inhibition of carbonic anhydrase IX activity, using compound SLC-149, displa...

New page

'''Unreleased structure'''

The entry 6nm0 is ON HOLD

Authors: Singh, S., McKenna, R.

Description: Selective inhibition of carbonic anhydrase IX activity, using compound SLC-149, displays limited anticancer effects in breast cancer cell lines
[[Category: Unreleased Structures]]
[[Category: Mckenna, R]]
[[Category: Singh, S]]

6nm0 - Revision history

OCA at 06:56, 11 October 2023

OCA at 09:04, 21 July 2021

OCA at 13:42, 27 February 2019

OCA: Protected "6nm0" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 6nm0 is ON HOLD Authors: Singh, S., McKenna, R. Description: Selective inhibition of carbonic anhydrase IX activity, using compound SLC-149, displa...