7ppf - Revision history

OCA at 13:07, 1 February 2024

2024-02-01T13:07:17Z

← Older revision		Revision as of 13:07, 1 February 2024
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	<StructureSection load='7ppf' size='340' side='right'caption='[[7ppf]], [[Resolution\|resolution]] 2.36Å' scene=''>		<StructureSection load='7ppf' size='340' side='right'caption='[[7ppf]], [[Resolution\|resolution]] 2.36Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7ppf]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7PPF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PPF FirstGlance]. <br>		<table><tr><td colspan='2'>[[7ppf]] is a 2 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=7PPF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PPF FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7YT:N-[4-[(4R)-1,4-dimethyl-6-oxidanylidene-4,5-dihydropyridazin-3-yl]phenyl]-5,7-dihydropyrrolo[3,4-b]pyridine-6-carboxamide'>7YT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 2.36Å</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Nicotinamide_phosphoribosyltransferase Nicotinamide phosphoribosyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.12 2.4.2.12] </span></td></tr>		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7YT:N-[4-[(4R)-1,4-dimethyl-6-oxidanylidene-4,5-dihydropyridazin-3-yl]phenyl]-5,7-dihydropyrrolo[3,4-b]pyridine-6-carboxamide'>7YT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=7ppf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ppf OCA], [https://pdbe.org/7ppf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ppf RCSB], [https://www.ebi.ac.uk/pdbsum/7ppf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ppf 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=7ppf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ppf OCA], [https://pdbe.org/7ppf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ppf RCSB], [https://www.ebi.ac.uk/pdbsum/7ppf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ppf ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/NAMPT_HUMAN NAMPT_HUMAN]] Catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, an intermediate in the biosynthesis of NAD. It is the rate limiting component in the mammalian NAD biosynthesis pathway (By similarity).		[https://www.uniprot.org/uniprot/NAMPT_HUMAN NAMPT_HUMAN] Catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, an intermediate in the biosynthesis of NAD. It is the rate limiting component in the mammalian NAD biosynthesis pathway (By similarity).
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 7ppf" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7ppf" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Phosphoribosyltransferase 3D structures\|Phosphoribosyltransferase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	~~[[Category: Nicotinamide phosphoribosyltransferase]]~~		[[Category: Hillig RC]]
	[[Category: Hillig~~, R C]]~~
	~~[[Category: Nmprtase]]~~
	~~[[Category: Small molecule inhibitor]]~~
	~~[[Category: Transferase~~]]

OCA at 09:54, 22 June 2022

2022-06-22T09:54:10Z

← Older revision		Revision as of 09:54, 22 June 2022
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	==CRYSTAL STRUCTURE OF NAMPT IN COMPLEX WITH COMPOUND 8==		==CRYSTAL STRUCTURE OF NAMPT IN COMPLEX WITH COMPOUND 8==
	<StructureSection load='7ppf' size='340' side='right'caption='[[7ppf]]' scene=''>		<StructureSection load='7ppf' size='340' side='right'caption='[[7ppf]], [[Resolution\|resolution]] 2.36Å' 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=7PPF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PPF FirstGlance]. <br>		<table><tr><td colspan='2'>[[7ppf]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7PPF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PPF 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=7ppf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ppf OCA], [https://pdbe.org/7ppf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ppf RCSB], [https://www.ebi.ac.uk/pdbsum/7ppf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ppf ProSAT]</span></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7YT:N-[4-[(4R)-1,4-dimethyl-6-oxidanylidene-4,5-dihydropyridazin-3-yl]phenyl]-5,7-dihydropyrrolo[3,4-b]pyridine-6-carboxamide'>7YT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
			<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Nicotinamide_phosphoribosyltransferase Nicotinamide phosphoribosyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.12 2.4.2.12] </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=7ppf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ppf OCA], [https://pdbe.org/7ppf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ppf RCSB], [https://www.ebi.ac.uk/pdbsum/7ppf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ppf ProSAT]</span></td></tr>
	</table>		</table>
			== Function ==
			[[https://www.uniprot.org/uniprot/NAMPT_HUMAN NAMPT_HUMAN]] Catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, an intermediate in the biosynthesis of NAD. It is the rate limiting component in the mammalian NAD biosynthesis pathway (By similarity).
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Inhibition of intracellular nicotinamide phosphoribosyltransferase (NAMPT) represents a new mode of action for cancer-targeting antibody-drug conjugates (ADCs) with activity also in slowly proliferating cells. To extend the repertoire of available effector chemistries, we have developed a novel structural class of NAMPT inhibitors as ADC payloads. A structure-activity relationship-driven approach supported by protein structural information was pursued to identify a suitable attachment point for the linker to connect the NAMPT inhibitor with the antibody. Optimization of scaffolds and linker structures led to highly potent effector chemistries which were conjugated to antibodies targeting C4.4a (LYPD3), HER2 (c-erbB2), or B7H3 (CD276) and tested on antigen-positive and -negative cancer cell lines. Pharmacokinetic studies, including metabolite profiling, were performed to optimize the stability and selectivity of the ADCs and to evaluate potential bystander effects. Optimized NAMPTi-ADCs demonstrated potent in vivo antitumor efficacy in target antigen-expressing xenograft mouse models. This led to the development of highly potent NAMPT inhibitor ADCs with a very good selectivity profile compared with the corresponding isotype control ADCs. Moreover, we demonstrate horizontal line to our knowledge for the first time horizontal line the generation of NAMPTi payload metabolites from the NAMPTi-ADCs in vitro and in vivo. In conclusion, NAMPTi-ADCs represent an attractive new payload class designed for use in ADCs for the treatment of solid and hematological cancers.

			A Novel NAMPT Inhibitor-Based Antibody-Drug Conjugate Payload Class for Cancer Therapy.,Bohnke N, Berger M, Griebenow N, Rottmann A, Erkelenz M, Hammer S, Berndt S, Gunther J, Wengner AM, Stelte-Ludwig B, Mahlert C, Greven S, Dietz L, Jorissen H, Barak N, Bomer U, Hillig RC, Eberspaecher U, Weiske J, Giese A, Mumberg D, Nising CF, Weinmann H, Sommer A Bioconjug Chem. 2022 Jun 3. doi: 10.1021/acs.bioconjchem.2c00178. PMID:35658441<ref>PMID:35658441</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 7ppf" style="background-color:#fffaf0;"></div>
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Hillig RC]]		[[Category: Nicotinamide phosphoribosyltransferase]]
			[[Category: Hillig, R C]]
			[[Category: Nmprtase]]
			[[Category: Small molecule inhibitor]]
			[[Category: Transferase]]

OCA at 05:10, 15 June 2022

2022-06-15T05:10:34Z

← Older revision		Revision as of 05:10, 15 June 2022
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	~~'''Unreleased structure'''~~

	~~The entry~~ 7ppf is ~~ON HOLD until Paper Publication~~		==CRYSTAL STRUCTURE OF NAMPT IN COMPLEX WITH COMPOUND 8==
			<StructureSection load='7ppf' size='340' side='right'caption='[[7ppf]]' scene=''>
	~~Authors:~~		== Structural highlights ==
			<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7PPF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PPF FirstGlance]. <br>
	~~Description~~:		</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=7ppf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ppf OCA], [https://pdbe.org/7ppf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ppf RCSB], [https://www.ebi.ac.uk/pdbsum/7ppf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ppf ProSAT]</span></td></tr>
	[[Category: ~~Unreleased Structures~~]]		</table>
			__TOC__
			</StructureSection>
			[[Category: Large Structures]]
			[[Category: Hillig RC]]

OCA at 04:05, 6 October 2021

2021-10-06T04:05:20Z

← Older revision		Revision as of 04:05, 6 October 2021
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 7ppf is ON HOLD		The entry 7ppf is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7ppf" [edit=sysop:move=sysop]

2021-09-22T05:31:20Z

Protected "7ppf" [edit=sysop:move=sysop]

← Older revision	Revision as of 05:31, 22 September 2021
(No difference)

OCA: New page: '''Unreleased structure''' The entry 7ppf is ON HOLD Authors: Description: Category: Unreleased Structures

2021-09-22T05:31:19Z

New page: '''Unreleased structure''' The entry 7ppf is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7ppf is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]