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Receptor Information

>4m6q Chain B (length=470) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]

EFNILLATDSYKVTHYKQYPPNTSKVYSYFECREKVKYEETVFYGLQYIL
NKYLKGKVVTKEKIQEAKDVYKEHFQDDVFNEKGWNYILEKYDGHLPIEI
KAVPEGFVIPRGNVLFTVENTDPECYWLTNWIETILVQSWYPITVATNSR
EQKKILAKYLLETSGNLDGLEYKLHDFGYRGVSSQETAGIGASAHLVNFK
GTDTVAGLALIKKYYGTKDPVPGYSVPAAEHSTITAWGKDHEKDAFEHIV
TQFSSVPVSVVSDSYDIYNACEKIWGEDLRHLIVSRSTQAPLIIRPDSGN
PLDTVLKVLEILGKKFPVTENSKGYKLLPPYLRVIQGDGVDINTLQEIVE
GMKQKMWSIENIAFGSGGGLLQKLTRDLLNCSFKCSYVVTNGLGINVFKD
PVADPNKRSKKGRLSLHRTPAGNFVTLEEGKGDLEEYGQDLLHTVFKNGK
VTKSYSFDEIRKNAQLNIEL

Ligand ID

20T

InChI

InChI=1S/C26H24F3N4O10PS/c27-26(28,29)17-2-1-3-19(9-17)45(40,41)18-6-4-14(5-7-18)10-31-24(36)16-8-15-12-32-33(23(15)30-11-16)25-22(35)21(34)20(43-25)13-42-44(37,38)39/h1-9,11-12,20-22,25,34-35H,10,13H2,(H,31,36)(H2,37,38,39)/t20-,21-,22-,25-/m1/s1

InChIKey

MBKCNGJHWVWHDL-NMOFPLQQSA-N

SMILES

Software	SMILES
CACTVS 3.385	O[CH]1[CH](O)[CH](O[CH]1CO[P](O)(O)=O)n2ncc3cc(cnc23)C(=O)NCc4ccc(cc4)[S](=O)(=O)c5cccc(c5)C(F)(F)F
CACTVS 3.385	O[C@H]1[C@@H](O)[C@@H](O[C@@H]1CO[P](O)(O)=O)n2ncc3cc(cnc23)C(=O)NCc4ccc(cc4)[S](=O)(=O)c5cccc(c5)C(F)(F)F
ACDLabs 12.01	FC(F)(F)c1cc(ccc1)S(=O)(=O)c2ccc(cc2)CNC(=O)c3cc4cnn(c4nc3)C5OC(C(O)C5O)COP(=O)(O)O
OpenEye OEToolkits 1.7.6	c1cc(cc(c1)S(=O)(=O)c2ccc(cc2)CNC(=O)c3cc4cnn(c4nc3)[C@H]5[C@@H]([C@@H]([C@H](O5)COP(=O)(O)O)O)O)C(F)(F)F
OpenEye OEToolkits 1.7.6	c1cc(cc(c1)S(=O)(=O)c2ccc(cc2)CNC(=O)c3cc4cnn(c4nc3)C5C(C(C(O5)COP(=O)(O)O)O)O)C(F)(F)F

Formula

C26 H24 F3 N4 O10 P S

Name

1-(5-O-phosphono-beta-D-ribofuranosyl)-N-(4-{[3-(trifluoromethyl)phenyl]sulfonyl}benzyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide

PDB chain

4m6q Chain A Residue 601 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]

Receptor-Ligand Complex Structure

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Structure summary

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PDB	4m6q Identification of amides derived from 1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid as potent inhibitors of human nicotinamide phosphoribosyltransferase (NAMPT).
Resolution	2.406 Å
Binding residue (original residue number in PDB)	Y18 R392
Binding residue (residue number reindexed from 1)	Y11 R376
Annotation score	1
Binding affinity	MOAD: ic50=0.0061uM PDBbind-CN: -logKd/Ki=8.21,IC50=6.1nM

Enzyme Commision number

2.4.2.12: nicotinamide phosphoribosyltransferase.

	Molecular Function
GO:0005125	cytokine activity
GO:0005515	protein binding
GO:0016757	glycosyltransferase activity
GO:0042802	identical protein binding
GO:0047280	nicotinamide phosphoribosyltransferase activity

	Biological Process
GO:0007165	signal transduction
GO:0007267	cell-cell signaling
GO:0007623	circadian rhythm
GO:0008284	positive regulation of cell population proliferation
GO:0008286	insulin receptor signaling pathway
GO:0009435	NAD biosynthetic process
GO:0019363	pyridine nucleotide biosynthetic process
GO:0032922	circadian regulation of gene expression
GO:0034356	NAD biosynthesis via nicotinamide riboside salvage pathway
GO:0045944	positive regulation of transcription by RNA polymerase II
GO:0048511	rhythmic process
GO:0051770	positive regulation of nitric-oxide synthase biosynthetic process
GO:0060612	adipose tissue development

	Cellular Component
GO:0005576	extracellular region
GO:0005615	extracellular space
GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0016607	nuclear speck
GO:0030054	cell junction
GO:0070062	extracellular exosome

PDB	RCSB:4m6q, PDBe:4m6q, PDBj:4m6q
PDBsum	4m6q
PubMed	24021463
UniProt	P43490\|NAMPT_HUMAN Nicotinamide phosphoribosyltransferase (Gene Name=NAMPT)

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Structure of PDB 4m6q Chain B Binding Site BS01