6ecz - Revision history

OCA at 07:31, 1 May 2024

2024-05-01T07:31:04Z

←Older revision		Revision as of 07:31, 1 May 2024
Line 12:		Line 12:
	== Function ==		== 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>		[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 ==
-	Human carbonic anhydrases (CA, EC, 4.2.1.1) IX and XII are overexpressed in cancer cells as adaptive response to hypoxia and acidic conditions characteristic of many tumors. In addition, hypoxia facilitates the activity of specific oxido-reductases that may be exploited to selectively activate bioreductive prodrugs. Here, new selective CA IX/XII inhibitors, as analogues of the antitumor phase II drug SLC-0111 are described, namely ureido-substituted benzenesulfonamides appended with a nitro-aromatic moiety to yield an antiproliferative action increased by hypoxia. These compounds were screened for the inhibition of the ubiquitous hCA I/II and the target hCA IX/XII. Six X-ray crystallographies with CA II and IX/mimic allowed for the rationalization of the compounds inhibitory activity. The effects of some such compounds on the viability of HT-29, MDA-MB-231, and PC-3 human cancer cell lines in both normoxic and hypoxic conditions were examined, providing the initiation toward the development of hypoxia-activated antitumor CAIs.
-
-	4-Hydroxy-3-nitro-5-ureido-benzenesulfonamides Selectively Target the Tumor-Associated Carbonic Anhydrase Isoforms IX and XII Showing Hypoxia-Enhanced Antiproliferative Profiles.,Nocentini A, Trallori E, Singh S, Lomelino CL, Bartolucci G, Di Cesare Mannelli L, Ghelardini C, McKenna R, Gratteri P, Supuran CT J Med Chem. 2018 Nov 28. doi: 10.1021/acs.jmedchem.8b01504. PMID:30433782<ref>PMID:30433782</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 6ecz" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 06:23, 11 October 2023

2023-10-11T06:23:47Z

←Older revision		Revision as of 06:23, 11 October 2023
Line 3:		Line 3:
	<StructureSection load='6ecz' size='340' side='right'caption='[[6ecz]], [[Resolution\|resolution]] 2.21Å' scene=''>		<StructureSection load='6ecz' size='340' side='right'caption='[[6ecz]], [[Resolution\|resolution]] 2.21Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6ecz]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ECZ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6ECZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6ecz]] 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=6ECZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ECZ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=J4D:1-[3-nitro-2-oxidanyl-5-[oxidanyl(oxidanylidene)-$l^{4}-azanyl]sulfonyl-phenyl]-3-[2,3,4,5,6-pentakis(fluoranyl)phenyl]urea'>J4D</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene~~></td></tr>~~	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.21Å</td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Carbonate_dehydratase Carbonate dehydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.1 4.2.1.1] </span></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=J4D:1-[3-nitro-2-oxidanyl-5-[oxidanyl(oxidanylidene)-$l^{4}-azanyl]sulfonyl-phenyl]-3-[2,3,4,5,6-pentakis(fluoranyl)phenyl]urea'>J4D</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'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6ecz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ecz OCA], [~~http~~://pdbe.org/6ecz PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6ecz RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6ecz PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6ecz ProSAT]</span></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=6ecz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ecz OCA], [https://pdbe.org/6ecz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ecz RCSB], [https://www.ebi.ac.uk/pdbsum/6ecz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ecz ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/CAH2_HUMAN CAH2_HUMAN]] Defects in CA2 are the cause of osteopetrosis autosomal recessive type 3 (OPTB3) [MIM:[~~http~~://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>	+	[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 ==		== Function ==
-	[~~[http~~://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>	+	[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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 28:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Carbonate dehydratase]]~~	+	[[Category: Homo sapiens]]
-	~~[[Category: Human~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Bartolucci, G]]	+	[[Category: Bartolucci G]]
-	[[Category: Ghelardini, C]]	+	[[Category: Ghelardini C]]
-	[[Category: Gratteri, P]]	+	[[Category: Gratteri P]]
-	[[Category: Lomelino, C]]	+	[[Category: Lomelino C]]
-	[[Category: Lucarini, E]]	+	[[Category: Lucarini E]]
-	[[Category: Mannelli~~, L D.C~~]]	+	[[Category: Mannelli LDC]]
-	[[Category: McKenna, R]]	+	[[Category: McKenna R]]
-	[[Category: Nocentini, A]]	+	[[Category: Nocentini A]]
-	[[Category: Singh, S]]	+	[[Category: Singh S]]
-	[[Category: Supuran~~, C T]]~~	+	[[Category: Supuran CT]]
-	~~[[Category: Anti-proliferative]]~~	+
-	~~[[Category: Carbonic anhydrase ix]]~~	+
-	~~[[Category: Carbonic anhydrase xii]]~~	+
-	~~[[Category: Hypoxia]]~~	+
-	~~[[Category: Inhibition]]~~	+
-	~~[[Category: Lyase]]~~	+
-	~~[[Category: Lyase-lyas inhibitor complex~~]]	+

OCA at 09:09, 1 May 2019

2019-05-01T09:09:50Z

←Older revision		Revision as of 09:09, 1 May 2019
Line 1:		Line 1:

	==Bioreductive 4-hydroxy-3-nitro-5-ureido-benzenesulfonamides selectively target the tumor-associated carbonic anhydrase isoforms IX and XII and show hypoxia-enhanced cytotoxicity against human cancer cell lines.==		==Bioreductive 4-hydroxy-3-nitro-5-ureido-benzenesulfonamides selectively target the tumor-associated carbonic anhydrase isoforms IX and XII and show hypoxia-enhanced cytotoxicity against human cancer cell lines.==
-	<StructureSection load='6ecz' size='340' side='right' caption='[[6ecz]], [[Resolution\|resolution]] 2.21Å' scene=''>	+	<StructureSection load='6ecz' size='340' side='right'caption='[[6ecz]], [[Resolution\|resolution]] 2.21Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6ecz]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ECZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ECZ FirstGlance]. <br>		<table><tr><td colspan='2'>[[6ecz]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ECZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ECZ FirstGlance]. <br>
Line 21:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 6ecz" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6ecz" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Carbonic anhydrase 3D structures\|Carbonic anhydrase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 27:		Line 30:
	[[Category: Carbonate dehydratase]]		[[Category: Carbonate dehydratase]]
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Bartolucci, G]]		[[Category: Bartolucci, G]]
	[[Category: Ghelardini, C]]		[[Category: Ghelardini, C]]

OCA at 20:28, 2 December 2018

2018-12-02T20:28:36Z

←Older revision		Revision as of 20:28, 2 December 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6ecz is ~~ON HOLD~~	+	==Bioreductive 4-hydroxy-3-nitro-5-ureido-benzenesulfonamides selectively target the tumor-associated carbonic anhydrase isoforms IX and XII and show hypoxia-enhanced cytotoxicity against human cancer cell lines.==
		+	<StructureSection load='6ecz' size='340' side='right' caption='[[6ecz]], [[Resolution\|resolution]] 2.21Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6ecz]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ECZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ECZ FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=J4D:1-[3-nitro-2-oxidanyl-5-[oxidanyl(oxidanylidene)-$l^{4}-azanyl]sulfonyl-phenyl]-3-[2,3,4,5,6-pentakis(fluoranyl)phenyl]urea'>J4D</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Carbonate_dehydratase Carbonate dehydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.1 4.2.1.1] </span></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=6ecz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ecz OCA], [http://pdbe.org/6ecz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ecz RCSB], [http://www.ebi.ac.uk/pdbsum/6ecz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ecz ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/CAH2_HUMAN CAH2_HUMAN]] Defects in CA2 are the cause of osteopetrosis autosomal recessive type 3 (OPTB3) [MIM:[http://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 ==
		+	[[http://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 ==
		+	Human carbonic anhydrases (CA, EC, 4.2.1.1) IX and XII are overexpressed in cancer cells as adaptive response to hypoxia and acidic conditions characteristic of many tumors. In addition, hypoxia facilitates the activity of specific oxido-reductases that may be exploited to selectively activate bioreductive prodrugs. Here, new selective CA IX/XII inhibitors, as analogues of the antitumor phase II drug SLC-0111 are described, namely ureido-substituted benzenesulfonamides appended with a nitro-aromatic moiety to yield an antiproliferative action increased by hypoxia. These compounds were screened for the inhibition of the ubiquitous hCA I/II and the target hCA IX/XII. Six X-ray crystallographies with CA II and IX/mimic allowed for the rationalization of the compounds inhibitory activity. The effects of some such compounds on the viability of HT-29, MDA-MB-231, and PC-3 human cancer cell lines in both normoxic and hypoxic conditions were examined, providing the initiation toward the development of hypoxia-activated antitumor CAIs.

-	~~Authors: Singh, S., McKenna, R., Supuran, C.T~~., Nocentini, A., ~~Lomelino~~, C., ~~Lucarini, E.~~, Bartolucci, G., Mannelli, L~~.D.C.~~, Ghelardini, C., Gratteri, P.	+	4-Hydroxy-3-nitro-5-ureido-benzenesulfonamides Selectively Target the Tumor-Associated Carbonic Anhydrase Isoforms IX and XII Showing Hypoxia-Enhanced Antiproliferative Profiles.,Nocentini A, Trallori E, Singh S, Lomelino CL, Bartolucci G, Di Cesare Mannelli L, Ghelardini C, McKenna R, Gratteri P, Supuran CT J Med Chem. 2018 Nov 28. doi: 10.1021/acs.jmedchem.8b01504. PMID:30433782<ref>PMID:30433782</ref>

-	~~Description: Bioreductive 4-hydroxy-3-nitro-5-ureido-benzenesulfonamides selectively target~~ the ~~tumor-associated carbonic anhydrase isoforms IX and XII and show hypoxia-enhanced cytotoxicity against human cancer cell lines~~.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category: Unreleased Structures]]~~	+	</div>
-	~~[[Category~~: ~~Nocentini, A]]~~	+	<div class="pdbe-citations 6ecz" style="background-color:#fffaf0;"></div>
-	~~[[Category: Ghelardini, C]]~~	+	== References ==
-	~~[[Category: Lucarini, E]]~~	+	<references/>
-	~~[[Category: Mannelli, L.D.C]]~~	+	__TOC__
-	[[Category: ~~Supuran, C.T~~]]	+	</StructureSection>
-	[[Category: ~~Mckenna, R~~]]	+	[[Category: Carbonate dehydratase]]
		+	[[Category: Human]]
	[[Category: Bartolucci, G]]		[[Category: Bartolucci, G]]
-	[[Category: ~~Lomelino~~, C]]	+	[[Category: Ghelardini, C]]
	[[Category: Gratteri, P]]		[[Category: Gratteri, P]]
		+	[[Category: Lomelino, C]]
		+	[[Category: Lucarini, E]]
		+	[[Category: Mannelli, L D.C]]
		+	[[Category: McKenna, R]]
		+	[[Category: Nocentini, A]]
	[[Category: Singh, S]]		[[Category: Singh, S]]
		+	[[Category: Supuran, C T]]
		+	[[Category: Anti-proliferative]]
		+	[[Category: Carbonic anhydrase ix]]
		+	[[Category: Carbonic anhydrase xii]]
		+	[[Category: Hypoxia]]
		+	[[Category: Inhibition]]
		+	[[Category: Lyase]]
		+	[[Category: Lyase-lyas inhibitor complex]]

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

2018-08-15T14:54:30Z

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

←Older revision

Revision as of 14:54, 15 August 2018

OCA: New page: '''Unreleased structure''' The entry 6ecz is ON HOLD Authors: Singh, S., McKenna, R., Supuran, C.T., Nocentini, A., Lomelino, C., Lucarini, E., Bartolucci, G., Mannelli, L.D.C., Ghelard...

2018-08-15T14:54:29Z

New page: '''Unreleased structure''' The entry 6ecz is ON HOLD Authors: Singh, S., McKenna, R., Supuran, C.T., Nocentini, A., Lomelino, C., Lucarini, E., Bartolucci, G., Mannelli, L.D.C., Ghelard...

New page

'''Unreleased structure'''

The entry 6ecz is ON HOLD

Authors: Singh, S., McKenna, R., Supuran, C.T., Nocentini, A., Lomelino, C., Lucarini, E., Bartolucci, G., Mannelli, L.D.C., Ghelardini, C., Gratteri, P.

Description: Bioreductive 4-hydroxy-3-nitro-5-ureido-benzenesulfonamides selectively target the tumor-associated carbonic anhydrase isoforms IX and XII and show hypoxia-enhanced cytotoxicity against human cancer cell lines.
[[Category: Unreleased Structures]]
[[Category: Nocentini, A]]
[[Category: Ghelardini, C]]
[[Category: Lucarini, E]]
[[Category: Mannelli, L.D.C]]
[[Category: Supuran, C.T]]
[[Category: Mckenna, R]]
[[Category: Bartolucci, G]]
[[Category: Lomelino, C]]
[[Category: Gratteri, P]]
[[Category: Singh, S]]