5hlw - Revision history

OCA at 10:46, 16 August 2023

2023-08-16T10:46:32Z

←Older revision		Revision as of 10:46, 16 August 2023
Line 3:		Line 3:
	<StructureSection load='5hlw' size='340' side='right'caption='[[5hlw]], [[Resolution\|resolution]] 1.97Å' scene=''>		<StructureSection load='5hlw' size='340' side='right'caption='[[5hlw]], [[Resolution\|resolution]] 1.97Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5hlw]] 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=5HLW OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5HLW FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5hlw]] 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=5HLW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HLW FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=62E:1-[2-(1-ETHYLPIPERIDIN-4-YL)ETHYL]-3-(6-{[6-(THIOPHEN-2-YL)[1,2,4]TRIAZOLO[4,3-B]PYRIDAZIN-3-YL]SULFANYL}-1,3-BENZOTHIAZOL-2-YL)UREA'>62E</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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]] 1.97Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MET ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=62E:1-[2-(1-ETHYLPIPERIDIN-4-YL)ETHYL]-3-(6-{[6-(THIOPHEN-2-YL)[1,2,4]TRIAZOLO[4,3-B]PYRIDAZIN-3-YL]SULFANYL}-1,3-BENZOTHIAZOL-2-YL)UREA'>62E</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </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=5hlw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hlw OCA], [https://pdbe.org/5hlw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hlw RCSB], [https://www.ebi.ac.uk/pdbsum/5hlw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hlw ProSAT]</span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=5hlw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hlw OCA], [~~http~~://pdbe.org/5hlw PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5hlw RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5hlw PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5hlw ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/MET_HUMAN MET_HUMAN]] Note=Activation of MET after rearrangement with the TPR gene produces an oncogenic protein. Note=Defects in MET may be associated with gastric cancer. Defects in MET are a cause of hepatocellular carcinoma (HCC) [MIM:[~~http~~://omim.org/entry/114550 114550]].<ref>PMID:9927037</ref> Defects in MET are a cause of renal cell carcinoma papillary (RCCP) [MIM:[~~http~~://omim.org/entry/605074 605074]]. It is a subtype of renal cell carcinoma tending to show a tubulo-papillary architecture formed by numerous, irregular, finger-like projections of connective tissue. Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into common renal cell carcinoma (clear cell, non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma.<ref>PMID:9140397</ref> <ref>PMID:9563489</ref> <ref>PMID:10433944</ref> <ref>PMID:10417759</ref> <ref>PMID:10327054</ref> Note=A common allele in the promoter region of the MET shows genetic association with susceptibility to autism in some families. Functional assays indicate a decrease in MET promoter activity and altered binding of specific transcription factor complexes. Note=MET activating mutations may be involved in the development of a highly malignant, metastatic syndrome known as cancer of unknown primary origin (CUP) or primary occult malignancy. Systemic neoplastic spread is generally a late event in cancer progression. However, in some instances, distant dissemination arises at a very early stage, so that metastases reach clinical relevance before primary lesions. Sometimes, the primary lesions cannot be identified in spite of the progresses in the diagnosis of malignancies.<ref>PMID:20949619</ref>	+	[https://www.uniprot.org/uniprot/MET_HUMAN MET_HUMAN] Note=Activation of MET after rearrangement with the TPR gene produces an oncogenic protein. Note=Defects in MET may be associated with gastric cancer. Defects in MET are a cause of hepatocellular carcinoma (HCC) [MIM:[https://omim.org/entry/114550 114550].<ref>PMID:9927037</ref> Defects in MET are a cause of renal cell carcinoma papillary (RCCP) [MIM:[https://omim.org/entry/605074 605074]. It is a subtype of renal cell carcinoma tending to show a tubulo-papillary architecture formed by numerous, irregular, finger-like projections of connective tissue. Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into common renal cell carcinoma (clear cell, non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma.<ref>PMID:9140397</ref> <ref>PMID:9563489</ref> <ref>PMID:10433944</ref> <ref>PMID:10417759</ref> <ref>PMID:10327054</ref> Note=A common allele in the promoter region of the MET shows genetic association with susceptibility to autism in some families. Functional assays indicate a decrease in MET promoter activity and altered binding of specific transcription factor complexes. Note=MET activating mutations may be involved in the development of a highly malignant, metastatic syndrome known as cancer of unknown primary origin (CUP) or primary occult malignancy. Systemic neoplastic spread is generally a late event in cancer progression. However, in some instances, distant dissemination arises at a very early stage, so that metastases reach clinical relevance before primary lesions. Sometimes, the primary lesions cannot be identified in spite of the progresses in the diagnosis of malignancies.<ref>PMID:20949619</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/MET_HUMAN MET_HUMAN]] Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including proliferation, scattering, morphogenesis and survival. Ligand binding at the cell surface induces autophosphorylation of MET on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or the adapter GAB1. Recruitment of these downstream effectors by MET leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. The RAS-ERK activation is associated with the morphogenetic effects while PI3K/AKT coordinates prosurvival effects. During embryonic development, MET signaling plays a role in gastrulation, development and migration of muscles and neuronal precursors, angiogenesis and kidney formation. In adults, participates in wound healing as well as organ regeneration and tissue remodeling. Promotes also differentiation and proliferation of hematopoietic cells.<ref>PMID:1846706</ref> <ref>PMID:8182137</ref> <ref>PMID:15314156</ref> Acts as a receptor for Listeria internalin inlB, mediating entry of the pathogen into cells.<ref>PMID:1846706</ref> <ref>PMID:8182137</ref> <ref>PMID:15314156</ref>	+	[https://www.uniprot.org/uniprot/MET_HUMAN MET_HUMAN] Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including proliferation, scattering, morphogenesis and survival. Ligand binding at the cell surface induces autophosphorylation of MET on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or the adapter GAB1. Recruitment of these downstream effectors by MET leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. The RAS-ERK activation is associated with the morphogenetic effects while PI3K/AKT coordinates prosurvival effects. During embryonic development, MET signaling plays a role in gastrulation, development and migration of muscles and neuronal precursors, angiogenesis and kidney formation. In adults, participates in wound healing as well as organ regeneration and tissue remodeling. Promotes also differentiation and proliferation of hematopoietic cells.<ref>PMID:1846706</ref> <ref>PMID:8182137</ref> <ref>PMID:15314156</ref> Acts as a receptor for Listeria internalin inlB, mediating entry of the pathogen into cells.<ref>PMID:1846706</ref> <ref>PMID:8182137</ref> <ref>PMID:15314156</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 29:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Receptor protein-tyrosine kinase]]~~	+	[[Category: Houtmann J]]
-	[[Category: Houtmann, J]]	+	[[Category: Marquette JP]]
-	[[Category: Marquette~~, J P~~]]	+	[[Category: Pouzieux S]]
-	[[Category: Pouzieux, S]]	+	[[Category: Vallee F]]
-	[[Category: Vallee, F]]	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Transferase inhibitor~~]]	+

OCA at 08:22, 27 May 2020

2020-05-27T08:22:13Z

←Older revision		Revision as of 08:22, 27 May 2020
Line 1:		Line 1:

	==Crystal structure of c-Met mutant Y1230H in complex with compound 14==		==Crystal structure of c-Met mutant Y1230H in complex with compound 14==
-	<StructureSection load='5hlw' size='340' side='right' caption='[[5hlw]], [[Resolution\|resolution]] 1.97Å' scene=''>	+	<StructureSection load='5hlw' size='340' side='right'caption='[[5hlw]], [[Resolution\|resolution]] 1.97Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5hlw]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HLW OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca.weizmann.ac~~.~~il/oca-docs~~/fgij/fg.htm?mol=5HLW FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5hlw]] 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=5HLW OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5HLW FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=62E:1-[2-(1-ETHYLPIPERIDIN-4-YL)ETHYL]-3-(6-{[6-(THIOPHEN-2-YL)[1,2,4]TRIAZOLO[4,3-B]PYRIDAZIN-3-YL]SULFANYL}-1,3-BENZOTHIAZOL-2-YL)UREA'>62E</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=62E:1-[2-(1-ETHYLPIPERIDIN-4-YL)ETHYL]-3-(6-{[6-(THIOPHEN-2-YL)[1,2,4]TRIAZOLO[4,3-B]PYRIDAZIN-3-YL]SULFANYL}-1,3-BENZOTHIAZOL-2-YL)UREA'>62E</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MET ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </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=5hlw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hlw OCA], [http://pdbe.org/5hlw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hlw RCSB], [http://www.ebi.ac.uk/pdbsum/5hlw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hlw ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5hlw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hlw OCA], [http://pdbe.org/5hlw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hlw RCSB], [http://www.ebi.ac.uk/pdbsum/5hlw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hlw ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 22:
	</div>		</div>
	<div class="pdbe-citations 5hlw" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5hlw" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Hepatocyte growth factor receptor 3D structures\|Hepatocyte growth factor receptor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
	[[Category: Houtmann, J]]		[[Category: Houtmann, J]]

OCA at 10:54, 10 December 2016

2016-12-10T10:54:26Z

←Older revision		Revision as of 10:54, 10 December 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5hlw is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal structure of c-Met mutant Y1230H in complex with compound 14==
		+	<StructureSection load='5hlw' size='340' side='right' caption='[[5hlw]], [[Resolution\|resolution]] 1.97Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5hlw]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HLW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HLW FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=62E:1-[2-(1-ETHYLPIPERIDIN-4-YL)ETHYL]-3-(6-{[6-(THIOPHEN-2-YL)[1,2,4]TRIAZOLO[4,3-B]PYRIDAZIN-3-YL]SULFANYL}-1,3-BENZOTHIAZOL-2-YL)UREA'>62E</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </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=5hlw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hlw OCA], [http://pdbe.org/5hlw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hlw RCSB], [http://www.ebi.ac.uk/pdbsum/5hlw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hlw ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/MET_HUMAN MET_HUMAN]] Note=Activation of MET after rearrangement with the TPR gene produces an oncogenic protein. Note=Defects in MET may be associated with gastric cancer. Defects in MET are a cause of hepatocellular carcinoma (HCC) [MIM:[http://omim.org/entry/114550 114550]].<ref>PMID:9927037</ref> Defects in MET are a cause of renal cell carcinoma papillary (RCCP) [MIM:[http://omim.org/entry/605074 605074]]. It is a subtype of renal cell carcinoma tending to show a tubulo-papillary architecture formed by numerous, irregular, finger-like projections of connective tissue. Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into common renal cell carcinoma (clear cell, non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma.<ref>PMID:9140397</ref> <ref>PMID:9563489</ref> <ref>PMID:10433944</ref> <ref>PMID:10417759</ref> <ref>PMID:10327054</ref> Note=A common allele in the promoter region of the MET shows genetic association with susceptibility to autism in some families. Functional assays indicate a decrease in MET promoter activity and altered binding of specific transcription factor complexes. Note=MET activating mutations may be involved in the development of a highly malignant, metastatic syndrome known as cancer of unknown primary origin (CUP) or primary occult malignancy. Systemic neoplastic spread is generally a late event in cancer progression. However, in some instances, distant dissemination arises at a very early stage, so that metastases reach clinical relevance before primary lesions. Sometimes, the primary lesions cannot be identified in spite of the progresses in the diagnosis of malignancies.<ref>PMID:20949619</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/MET_HUMAN MET_HUMAN]] Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including proliferation, scattering, morphogenesis and survival. Ligand binding at the cell surface induces autophosphorylation of MET on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or the adapter GAB1. Recruitment of these downstream effectors by MET leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. The RAS-ERK activation is associated with the morphogenetic effects while PI3K/AKT coordinates prosurvival effects. During embryonic development, MET signaling plays a role in gastrulation, development and migration of muscles and neuronal precursors, angiogenesis and kidney formation. In adults, participates in wound healing as well as organ regeneration and tissue remodeling. Promotes also differentiation and proliferation of hematopoietic cells.<ref>PMID:1846706</ref> <ref>PMID:8182137</ref> <ref>PMID:15314156</ref> Acts as a receptor for Listeria internalin inlB, mediating entry of the pathogen into cells.<ref>PMID:1846706</ref> <ref>PMID:8182137</ref> <ref>PMID:15314156</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The HGF/MET pathway is frequently activated in a variety of cancer types. Several selective small molecule inhibitors of the MET kinase are currently in clinical evaluation, in particular for NSCLC, liver, and gastric cancer patients. We report herein the discovery of a series of triazolopyridazines that are selective inhibitors of wild-type (WT) MET kinase and several clinically relevant mutants. We provide insight into their mode of binding and report unprecedented crystal structures of the Y1230H variant. A multiparametric chemical optimization approach allowed the identification of compound 12 (SAR125844) as a development candidate. In this chemical series, absence of CYP3A4 inhibition was obtained at the expense of satisfactory oral absorption. Compound 12, a promising parenteral agent for the treatment of MET-dependent cancers, promoted sustained target engagement at tolerated doses in a human xenograft tumor model. Preclinical pharmacokinetics conducted in several species were predictive for the observed pharmacokinetic behavior of 12 in cancer patients.

-	~~Authors: Vallee~~, F., ~~Pouzieux~~, S., ~~Marquette~~, J.P., ~~Houtmann, J~~.	+	Discovery and Pharmacokinetic and Pharmacological Properties of the Potent and Selective MET Kinase Inhibitor 1-{6-[6-(4-Fluorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl]benzothiazo l-2-yl}-3-(2-morpholin-4-ylethyl)urea (SAR125844).,Ugolini A, Kenigsberg M, Rak A, Vallee F, Houtmann J, Lowinski M, Capdevila C, Khider J, Albert E, Martinet N, Nemecek C, Grapinet S, Bacque E, Roesner M, Delaisi C, Calvet L, Bonche F, Semiond D, Egile C, Goulaouic H, Schio L J Med Chem. 2016 Aug 11;59(15):7066-74. doi: 10.1021/acs.jmedchem.6b00280. Epub, 2016 Jul 13. PMID:27355974<ref>PMID:27355974</ref>

-	~~Description: Crystal structure~~ of ~~c-Met mutant Y1230H in complex with compound 14~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
-	[[Category: ~~Marquette, J.P~~]]	+	<div class="pdbe-citations 5hlw" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Receptor protein-tyrosine kinase]]
	[[Category: Houtmann, J]]		[[Category: Houtmann, J]]
-	[[Category: ~~Vallee~~, F]]	+	[[Category: Marquette, J P]]
	[[Category: Pouzieux, S]]		[[Category: Pouzieux, S]]
		+	[[Category: Vallee, F]]
		+	[[Category: Transferase]]
		+	[[Category: Transferase inhibitor]]

OCA at 12:16, 9 September 2016

2016-09-09T12:16:50Z

←Older revision		Revision as of 12:16, 9 September 2016
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5hlw is ON HOLD	+	The entry 5hlw is ON HOLD until Paper Publication

	Authors: Vallee, F., Pouzieux, S., Marquette, J.P., Houtmann, J.		Authors: Vallee, F., Pouzieux, S., Marquette, J.P., Houtmann, J.

OCA: Protected "5hlw" [edit=sysop:move=sysop]

2016-01-28T00:51:05Z

Protected "5hlw" [edit=sysop:move=sysop]

←Older revision

Revision as of 00:51, 28 January 2016

OCA: New page: '''Unreleased structure''' The entry 5hlw is ON HOLD Authors: Vallee, F., Pouzieux, S., Marquette, J.P., Houtmann, J. Description: Crystal structure of c-Met mutant Y1230H in complex w...

2016-01-28T00:51:04Z

New page: '''Unreleased structure''' The entry 5hlw is ON HOLD Authors: Vallee, F., Pouzieux, S., Marquette, J.P., Houtmann, J. Description: Crystal structure of c-Met mutant Y1230H in complex w...

New page

'''Unreleased structure'''

The entry 5hlw is ON HOLD

Authors: Vallee, F., Pouzieux, S., Marquette, J.P., Houtmann, J.

Description: Crystal structure of c-Met mutant Y1230H in complex with compound 14
[[Category: Unreleased Structures]]
[[Category: Marquette, J.P]]
[[Category: Houtmann, J]]
[[Category: Vallee, F]]
[[Category: Pouzieux, S]]