4lxd - Revision history

OCA at 12:22, 1 March 2024

OCA — Fri, 01 Mar 2024 12:22:36 GMT

←Older revision		Revision as of 12:22, 1 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4lxd]] 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=4LXD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LXD FirstGlance]. <br>		<table><tr><td colspan='2'>[[4lxd]] 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=4LXD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LXD FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1XV:4-(4-{[4-(4-CHLOROPHENYL)-5,6-DIHYDRO-2H-PYRAN-3-YL]METHYL}PIPERAZIN-1-YL)-N-{[3-NITRO-4-(TETRAHYDRO-2H-PYRAN-4-YLAMINO)PHENYL]SULFONYL}BENZAMIDE'>1XV</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]] 1.9Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1XV:4-(4-{[4-(4-CHLOROPHENYL)-5,6-DIHYDRO-2H-PYRAN-3-YL]METHYL}PIPERAZIN-1-YL)-N-{[3-NITRO-4-(TETRAHYDRO-2H-PYRAN-4-YLAMINO)PHENYL]SULFONYL}BENZAMIDE'>1XV</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=4lxd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lxd OCA], [https://pdbe.org/4lxd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lxd RCSB], [https://www.ebi.ac.uk/pdbsum/4lxd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lxd 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=4lxd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lxd OCA], [https://pdbe.org/4lxd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lxd RCSB], [https://www.ebi.ac.uk/pdbsum/4lxd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lxd ProSAT]</span></td></tr>
	</table>		</table>
Line 11:		Line 12:
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/BCL2_HUMAN BCL2_HUMAN] Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1).<ref>PMID:18570871</ref>		[https://www.uniprot.org/uniprot/BCL2_HUMAN BCL2_HUMAN] Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1).<ref>PMID:18570871</ref>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Proteins in the B cell CLL/lymphoma 2 (BCL-2) family are key regulators of the apoptotic process. This family comprises proapoptotic and prosurvival proteins, and shifting the balance toward the latter is an established mechanism whereby cancer cells evade apoptosis. The therapeutic potential of directly inhibiting prosurvival proteins was unveiled with the development of navitoclax, a selective inhibitor of both BCL-2 and BCL-2-like 1 (BCL-X(L)), which has shown clinical efficacy in some BCL-2-dependent hematological cancers. However, concomitant on-target thrombocytopenia caused by BCL-X(L) inhibition limits the efficacy achievable with this agent. Here we report the re-engineering of navitoclax to create a highly potent, orally bioavailable and BCL-2-selective inhibitor, ABT-199. This compound inhibits the growth of BCL-2-dependent tumors in vivo and spares human platelets. A single dose of ABT-199 in three patients with refractory chronic lymphocytic leukemia resulted in tumor lysis within 24 h. These data indicate that selective pharmacological inhibition of BCL-2 shows promise for the treatment of BCL-2-dependent hematological cancers.
-
-	ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets.,Souers AJ, Leverson JD, Boghaert ER, Ackler SL, Catron ND, Chen J, Dayton BD, Ding H, Enschede SH, Fairbrother WJ, Huang DC, Hymowitz SG, Jin S, Khaw SL, Kovar PJ, Lam LT, Lee J, Maecker HL, Marsh KC, Mason KD, Mitten MJ, Nimmer PM, Oleksijew A, Park CH, Park CM, Phillips DC, Roberts AW, Sampath D, Seymour JF, Smith ML, Sullivan GM, Tahir SK, Tse C, Wendt MD, Xiao Y, Xue JC, Zhang H, Humerickhouse RA, Rosenberg SH, Elmore SW Nat Med. 2013 Feb;19(2):202-8. doi: 10.1038/nm.3048. Epub 2013 Jan 6. PMID:23291630<ref>PMID:23291630</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4lxd" style="background-color:#fffaf0;"></div>

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

OCA at 10:38, 21 December 2022

OCA — Wed, 21 Dec 2022 10:38:41 GMT

←Older revision		Revision as of 10:38, 21 December 2022
Line 1:		Line 1:

	==Bcl_2-Navitoclax Analog (without Thiophenyl) Complex==		==Bcl_2-Navitoclax Analog (without Thiophenyl) Complex==
-	<StructureSection load='4lxd' size='340' side='right' caption='[[4lxd]], [[Resolution\|resolution]] 1.90Å' scene=''>	+	<StructureSection load='4lxd' size='340' side='right'caption='[[4lxd]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4lxd]] 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=4LXD OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4LXD FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4lxd]] 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=4LXD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LXD FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1XV:4-(4-{[4-(4-CHLOROPHENYL)-5,6-DIHYDRO-2H-PYRAN-3-YL]METHYL}PIPERAZIN-1-YL)-N-{[3-NITRO-4-(TETRAHYDRO-2H-PYRAN-4-YLAMINO)PHENYL]SULFONYL}BENZAMIDE'>1XV</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1XV:4-(4-{[4-(4-CHLOROPHENYL)-5,6-DIHYDRO-2H-PYRAN-3-YL]METHYL}PIPERAZIN-1-YL)-N-{[3-NITRO-4-(TETRAHYDRO-2H-PYRAN-4-YLAMINO)PHENYL]SULFONYL}BENZAMIDE'>1XV</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4lvt\|4lvt]], [[4lxe\|4lxe]]</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=4lxd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lxd OCA], [https://pdbe.org/4lxd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lxd RCSB], [https://www.ebi.ac.uk/pdbsum/4lxd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lxd ProSAT]</span></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BCL2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~</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=4lxd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lxd OCA], [~~http~~://pdbe.org/4lxd PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4lxd RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4lxd PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4lxd ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/BCL2_HUMAN BCL2_HUMAN]] Note=A chromosomal aberration involving BCL2 has been found in chronic lymphatic leukemia. Translocation t(14;18)(q32;q21) with immunoglobulin gene regions. BCL2 mutations found in non-Hodgkin lymphomas carrying the chromosomal translocation could be attributed to the Ig somatic hypermutation mechanism resulting in nucleotide transitions.	+	[https://www.uniprot.org/uniprot/BCL2_HUMAN BCL2_HUMAN] Note=A chromosomal aberration involving BCL2 has been found in chronic lymphatic leukemia. Translocation t(14;18)(q32;q21) with immunoglobulin gene regions. BCL2 mutations found in non-Hodgkin lymphomas carrying the chromosomal translocation could be attributed to the Ig somatic hypermutation mechanism resulting in nucleotide transitions.
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/BCL2_HUMAN BCL2_HUMAN]] Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1).<ref>PMID:18570871</ref>	+	[https://www.uniprot.org/uniprot/BCL2_HUMAN BCL2_HUMAN] Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1).<ref>PMID:18570871</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 4lxd" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4lxd" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[B-cell lymphoma proteins 3D structures\|B-cell lymphoma proteins 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Park, C H~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Helice]]~~	+	[[Category: Park CH]]
-	~~[[Category: Apoptosis regulator-inhibitor complex~~]]	+

OCA at 02:48, 16 November 2017

OCA — Thu, 16 Nov 2017 02:48:04 GMT

←Older revision		Revision as of 02:48, 16 November 2017
Line 22:		Line 22:
	</div>		</div>
	<div class="pdbe-citations 4lxd" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4lxd" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Bcl-2\|Bcl-2]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 12:37, 11 August 2016

OCA — Thu, 11 Aug 2016 12:37:47 GMT

←Older revision		Revision as of 12:37, 11 August 2016
Line 1:		Line 1:
		+
	==Bcl_2-Navitoclax Analog (without Thiophenyl) Complex==		==Bcl_2-Navitoclax Analog (without Thiophenyl) Complex==
	<StructureSection load='4lxd' size='340' side='right' caption='[[4lxd]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='4lxd' size='340' side='right' caption='[[4lxd]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4lxd]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Ochroconis_lascauxensis Ochroconis lascauxensis~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LXD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LXD FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4lxd]] 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=4LXD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LXD FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1XV:4-(4-{[4-(4-CHLOROPHENYL)-5,6-DIHYDRO-2H-PYRAN-3-YL]METHYL}PIPERAZIN-1-YL)-N-{[3-NITRO-4-(TETRAHYDRO-2H-PYRAN-4-YLAMINO)PHENYL]SULFONYL}BENZAMIDE'>1XV</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1XV:4-(4-{[4-(4-CHLOROPHENYL)-5,6-DIHYDRO-2H-PYRAN-3-YL]METHYL}PIPERAZIN-1-YL)-N-{[3-NITRO-4-(TETRAHYDRO-2H-PYRAN-4-YLAMINO)PHENYL]SULFONYL}BENZAMIDE'>1XV</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4lvt\|4lvt]], [[4lxe\|4lxe]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4lvt\|4lvt]], [[4lxe\|4lxe]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BCL2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=~~994323 Ochroconis lascauxensis~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BCL2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4lxd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lxd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4lxd RCSB], [http://www.ebi.ac.uk/pdbsum/4lxd PDBsum]</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=4lxd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lxd OCA], [http://pdbe.org/4lxd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4lxd RCSB], [http://www.ebi.ac.uk/pdbsum/4lxd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4lxd ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 21:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4lxd" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 27:		Line 29:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Ochroconis lascauxensis~~]]	+	[[Category: Human]]
	[[Category: Park, C H]]		[[Category: Park, C H]]
	[[Category: Helice]]		[[Category: Helice]]
	[[Category: Apoptosis regulator-inhibitor complex]]		[[Category: Apoptosis regulator-inhibitor complex]]

OCA at 10:18, 25 January 2015

OCA — Sun, 25 Jan 2015 10:18:21 GMT

←Older revision		Revision as of 10:18, 25 January 2015
Line 1:		Line 1:
-	~~{{STRUCTURE_4lxd\| PDB=4lxd \| SCENE= }}~~	+	==Bcl_2-Navitoclax Analog (without Thiophenyl) Complex==
-	===Bcl_2-Navitoclax Analog (without Thiophenyl) Complex===	+	<StructureSection load='4lxd' size='340' side='right' caption='[[4lxd]], [[Resolution\|resolution]] 1.90Å' scene=''>
-	{{~~ABSTRACT_PUBMED_23291630}~~}	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4lxd]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Ochroconis_lascauxensis Ochroconis lascauxensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LXD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LXD FirstGlance]. <br>
-	==Disease==	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1XV:4-(4-{[4-(4-CHLOROPHENYL)-5,6-DIHYDRO-2H-PYRAN-3-YL]METHYL}PIPERAZIN-1-YL)-N-{[3-NITRO-4-(TETRAHYDRO-2H-PYRAN-4-YLAMINO)PHENYL]SULFONYL}BENZAMIDE'>1XV</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4lvt\|4lvt]], [[4lxe\|4lxe]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BCL2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=994323 Ochroconis lascauxensis])</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=4lxd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lxd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4lxd RCSB], [http://www.ebi.ac.uk/pdbsum/4lxd PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
	[[http://www.uniprot.org/uniprot/BCL2_HUMAN BCL2_HUMAN]] Note=A chromosomal aberration involving BCL2 has been found in chronic lymphatic leukemia. Translocation t(14;18)(q32;q21) with immunoglobulin gene regions. BCL2 mutations found in non-Hodgkin lymphomas carrying the chromosomal translocation could be attributed to the Ig somatic hypermutation mechanism resulting in nucleotide transitions.		[[http://www.uniprot.org/uniprot/BCL2_HUMAN BCL2_HUMAN]] Note=A chromosomal aberration involving BCL2 has been found in chronic lymphatic leukemia. Translocation t(14;18)(q32;q21) with immunoglobulin gene regions. BCL2 mutations found in non-Hodgkin lymphomas carrying the chromosomal translocation could be attributed to the Ig somatic hypermutation mechanism resulting in nucleotide transitions.
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/BCL2_HUMAN BCL2_HUMAN]] Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1).<ref>PMID:18570871</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Proteins in the B cell CLL/lymphoma 2 (BCL-2) family are key regulators of the apoptotic process. This family comprises proapoptotic and prosurvival proteins, and shifting the balance toward the latter is an established mechanism whereby cancer cells evade apoptosis. The therapeutic potential of directly inhibiting prosurvival proteins was unveiled with the development of navitoclax, a selective inhibitor of both BCL-2 and BCL-2-like 1 (BCL-X(L)), which has shown clinical efficacy in some BCL-2-dependent hematological cancers. However, concomitant on-target thrombocytopenia caused by BCL-X(L) inhibition limits the efficacy achievable with this agent. Here we report the re-engineering of navitoclax to create a highly potent, orally bioavailable and BCL-2-selective inhibitor, ABT-199. This compound inhibits the growth of BCL-2-dependent tumors in vivo and spares human platelets. A single dose of ABT-199 in three patients with refractory chronic lymphocytic leukemia resulted in tumor lysis within 24 h. These data indicate that selective pharmacological inhibition of BCL-2 shows promise for the treatment of BCL-2-dependent hematological cancers.

-	~~==Function==~~	+	ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets.,Souers AJ, Leverson JD, Boghaert ER, Ackler SL, Catron ND, Chen J, Dayton BD, Ding H, Enschede SH, Fairbrother WJ, Huang DC, Hymowitz SG, Jin S, Khaw SL, Kovar PJ, Lam LT, Lee J, Maecker HL, Marsh KC, Mason KD, Mitten MJ, Nimmer PM, Oleksijew A, Park CH, Park CM, Phillips DC, Roberts AW, Sampath D, Seymour JF, Smith ML, Sullivan GM, Tahir SK, Tse C, Wendt MD, Xiao Y, Xue JC, Zhang H, Humerickhouse RA, Rosenberg SH, Elmore SW Nat Med. 2013 Feb;19(2):202-8. doi: 10.1038/nm.3048. Epub 2013 Jan 6. PMID:23291630<ref>PMID:23291630</ref>
-	~~[[http~~:~~//www~~.~~uniprot~~.~~org~~/~~uniprot/BCL2_HUMAN BCL2_HUMAN]] Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells~~. ~~Regulates cell death by controlling the mitochondrial membrane permeability~~. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1).<ref>PMID:~~18570871~~</ref>	+

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[4lxd]] is~~ a ~~1 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Ochroconis_lascauxensis Ochroconis lascauxensis]~~. ~~Full crystallographic information is available from [http:~~/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=4LXD OCA].~~	+	</div>

-	==~~Reference~~==	+	==See Also==
-	~~<ref group~~=~~"xtra">PMID:023291630</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	*[[Bcl-2\|Bcl-2]]
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Ochroconis lascauxensis]]		[[Category: Ochroconis lascauxensis]]
-	[[Category: Park, C H.]]	+	[[Category: Park, C H]]
-	[[Category: ~~8 helice~~]]	+	[[Category: Helice]]
	[[Category: Apoptosis regulator-inhibitor complex]]		[[Category: Apoptosis regulator-inhibitor complex]]

OCA at 07:48, 14 August 2013

OCA — Wed, 14 Aug 2013 07:48:09 GMT

←Older revision		Revision as of 07:48, 14 August 2013
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{STRUCTURE_4lxd\| PDB=4lxd \| SCENE= }}
		+	===Bcl_2-Navitoclax Analog (without Thiophenyl) Complex===
		+	{{ABSTRACT_PUBMED_23291630}}

-	~~The entry 4lxd is ON HOLD~~	+	==Disease==
		+	[[http://www.uniprot.org/uniprot/BCL2_HUMAN BCL2_HUMAN]] Note=A chromosomal aberration involving BCL2 has been found in chronic lymphatic leukemia. Translocation t(14;18)(q32;q21) with immunoglobulin gene regions. BCL2 mutations found in non-Hodgkin lymphomas carrying the chromosomal translocation could be attributed to the Ig somatic hypermutation mechanism resulting in nucleotide transitions.

-	~~Authors~~: ~~Park, C~~.H.	+	==Function==
		+	[[http://www.uniprot.org/uniprot/BCL2_HUMAN BCL2_HUMAN]] Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1).<ref>PMID:18570871</ref>

-	~~Description~~: ~~Bcl_2~~-~~Navitoclax Analog (without Thiophenyl) Complex~~	+	==About this Structure==
		+	[[4lxd]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Ochroconis_lascauxensis Ochroconis lascauxensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LXD OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:023291630</ref><references group="xtra"/><references/>
		+	[[Category: Ochroconis lascauxensis]]
		+	[[Category: Park, C H.]]
		+	[[Category: 8 helice]]
		+	[[Category: Apoptosis regulator-inhibitor complex]]

OCA: Protected "4lxd" [edit=sysop:move=sysop]

OCA — Wed, 07 Aug 2013 20:19:41 GMT

Protected "4lxd" [edit=sysop:move=sysop]

←Older revision

Revision as of 20:19, 7 August 2013

OCA: New page: '''Unreleased structure''' The entry 4lxd is ON HOLD Authors: Park, C.H. Description: Bcl_2-Navitoclax Analog (without Thiophenyl) Complex

OCA — Wed, 07 Aug 2013 20:19:40 GMT

New page: '''Unreleased structure''' The entry 4lxd is ON HOLD Authors: Park, C.H. Description: Bcl_2-Navitoclax Analog (without Thiophenyl) Complex

New page

'''Unreleased structure'''

The entry 4lxd is ON HOLD

Authors: Park, C.H.

Description: Bcl_2-Navitoclax Analog (without Thiophenyl) Complex