BRENDA - Enzyme Database show
show all sequences of 2.4.2.12

Pharmacological inhibition of nicotinamide phosphoribosyltransferase/visfatin enzymatic activity identifies a new inflammatory pathway linked to NAD

Busso, N.; Karababa, M.; Nobile, M.; Rolaz, A.; Van Gool, F.; Galli, M.; Leo, O.; So, A.; De Smedt, T.; PLoS ONE 3, e2267 (2008)

Data extracted from this reference:

Application
Application
Commentary
Organism
pharmacology
NAMPT inhibition might have therapeutic efficacy in immune-mediated inflammatory diseases through impact on inflammatory cytokine secretion by leukocytes
Homo sapiens
Inhibitors
Inhibitors
Commentary
Organism
Structure
APO866
also known as FK866, (E)-N-[4-(1-benzoylpiperidin-4-yl)butyl]-3-(pyridine-3-yl)-acrylamide, no impact on cell viability, dose-dependent reduction of levels of intracellular NAD in and secretion of TNFalpha, IL-1beta, IL-6 (pro-inflammatory cytokines) by monocyctes, monocyte-derived dendritic cells and total PBMCs upon stimulation of inflammatory response by 100 ng/ml lipopolysaccharide (LPS) or 5 microgram/ml Pansorbin (Staphylococcus aureus cells, SAC)
Homo sapiens
APO866
also known as FK866, (E)-N-[4-(1-benzoylpiperidin-4-yl)butyl]-3-(pyridine-3-yl)-acrylamide, 10 mg/kg, DBA/1 mice: beneficial effects on collagen-induced arthritis (CIA) due to impaired secretion of inflammatory cytokines (reduction of the mean arthritic score and number of affected paws from mice with CIA as well as decrease in local levels of IL-1beta and IL-6 but no impact on IL-10, IFN-gamma, CCL5 and IL-12p70 levels, decrease in inflammatory infiltrate and hyperplasia in knees and paws from mice with CIA) but not due to toxicity (no premature death of individuals, no impact on histology of liver, spleen, lung, gut, kidney, inguinal lymph nodes and brain, normal liver alanine aminotransferase levels, no enhanced apoptosis in arthritic paws) and not due to impact on anti-collagen immune response (similar anti-collagen IgG levels); also known as FK866, (E)-N-[4-(1-benzoylpiperidin-4-yl)butyl]-3-(pyridine-3-yl)-acrylamide, 10 mg/kg, isolated peritoneal exudate inflammatory cells (PEC) from C57BL/6 mice: time-dependent NAD depletion (lowest at 9 h, recovery after 14 h), addition of 10 mM NMN abolishes a reduction of intracellular NAD+ concentration as well as TNFalpha and IL-6 secretion (pro-inflammatory cytokines) in PECs induced by in vivo or in vitro stimulation of inflammatory response with 5 microgram/ml Pansorbin (Staphylococcus aureus cells, SAC) or 100 ng/ml lipopolysaccharide (LPS)
Mus musculus
Natural Substrates/ Products (Substrates)
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
nicotinamide + alpha-D-5-phosphoribosyl 1-diphosphate
Mus musculus
nicotinamide clearance
nicotinamide mononucleotide + diphosphate
NMN synthesis is rate-limiting step for NAD+ synthesis
-
r
nicotinamide + alpha-D-5-phosphoribosyl 1-diphosphate
Homo sapiens
nicotinamide clearance
nicotinamide mononucleotide + diphosphate
NMN synthesis is rate-limiting step for NAD+ synthesis
-
r
Organism
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
Homo sapiens
P43490
-
-
Mus musculus
Q99KQ4
male DBA/1 mice, naive or with collagen-induced arthritis (CIA) after immunization with type II collagen, and male and female C57BL/6 mice
-
Source Tissue
Source Tissue
Commentary
Organism
Textmining
blood vessel
positive staining in blood vessels from arthritic joints as revealed by immunohistochemistry using rat monoclonal anti-murine NAMPT antibody
Mus musculus
-
chondrocyte
some positive staining in cells of both normal and arthritic joints as revealed by immunohistochemistry using rat monoclonal anti-murine NAMPT antibody
Mus musculus
-
joint
massive expression in synoviocytes of the synovial lining layer, sub-intimal synovium and pannus in joints from mice with type II collagen induced arthritis (CIA) compared to non-arthritic naive DBA/1 mice as revealed by immunohistochemistry using rat monoclonal anti-murine NAMPT antibody, some positive staining in chondrocytes from normal and arthritic joints and in blood vessels and inflammatory cells from arthritic joints
Mus musculus
-
monocyte
isolated from total PBMCs from blood from healthy individuals
Homo sapiens
-
monocyte-derived dendritic cell
from blood from healthy individuals
Homo sapiens
-
paw
elevated levels in mice with type II collagen induced arthritis (CIA) compared to non-arthritic naive DBA/1 mice as revealed by ELISA using a mouse visfatin/PBEF ELISA kit
Mus musculus
-
peripheral blood mononuclear cell
PBMC from blood from healthy individuals
Homo sapiens
-
peritoneal exudate
(PEC) isolated from naive C57BL/6 mice of from lipopolysaccharide-treated mice
Mus musculus
-
serum
elevated levels upon type II collagen induced arthritis (CIA) compared to non-arthritic naive DBA/1 mice as revealed by ELISA using a mouse visfatin/PBEF ELISA kit
Mus musculus
-
Substrates and Products (Substrate)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
nicotinamide + alpha-D-5-phosphoribosyl 1-diphosphate
nicotinamide clearance
694813
Mus musculus
nicotinamide mononucleotide + diphosphate
NMN synthesis is rate-limiting step for NAD+ synthesis
-
-
r
nicotinamide + alpha-D-5-phosphoribosyl 1-diphosphate
nicotinamide clearance
694813
Homo sapiens
nicotinamide mononucleotide + diphosphate
NMN synthesis is rate-limiting step for NAD+ synthesis
-
-
r
Application (protein specific)
Application
Commentary
Organism
pharmacology
NAMPT inhibition might have therapeutic efficacy in immune-mediated inflammatory diseases through impact on inflammatory cytokine secretion by leukocytes
Homo sapiens
Inhibitors (protein specific)
Inhibitors
Commentary
Organism
Structure
APO866
also known as FK866, (E)-N-[4-(1-benzoylpiperidin-4-yl)butyl]-3-(pyridine-3-yl)-acrylamide, no impact on cell viability, dose-dependent reduction of levels of intracellular NAD in and secretion of TNFalpha, IL-1beta, IL-6 (pro-inflammatory cytokines) by monocyctes, monocyte-derived dendritic cells and total PBMCs upon stimulation of inflammatory response by 100 ng/ml lipopolysaccharide (LPS) or 5 microgram/ml Pansorbin (Staphylococcus aureus cells, SAC)
Homo sapiens
APO866
also known as FK866, (E)-N-[4-(1-benzoylpiperidin-4-yl)butyl]-3-(pyridine-3-yl)-acrylamide, 10 mg/kg, DBA/1 mice: beneficial effects on collagen-induced arthritis (CIA) due to impaired secretion of inflammatory cytokines (reduction of the mean arthritic score and number of affected paws from mice with CIA as well as decrease in local levels of IL-1beta and IL-6 but no impact on IL-10, IFN-gamma, CCL5 and IL-12p70 levels, decrease in inflammatory infiltrate and hyperplasia in knees and paws from mice with CIA) but not due to toxicity (no premature death of individuals, no impact on histology of liver, spleen, lung, gut, kidney, inguinal lymph nodes and brain, normal liver alanine aminotransferase levels, no enhanced apoptosis in arthritic paws) and not due to impact on anti-collagen immune response (similar anti-collagen IgG levels); also known as FK866, (E)-N-[4-(1-benzoylpiperidin-4-yl)butyl]-3-(pyridine-3-yl)-acrylamide, 10 mg/kg, isolated peritoneal exudate inflammatory cells (PEC) from C57BL/6 mice: time-dependent NAD depletion (lowest at 9 h, recovery after 14 h), addition of 10 mM NMN abolishes a reduction of intracellular NAD+ concentration as well as TNFalpha and IL-6 secretion (pro-inflammatory cytokines) in PECs induced by in vivo or in vitro stimulation of inflammatory response with 5 microgram/ml Pansorbin (Staphylococcus aureus cells, SAC) or 100 ng/ml lipopolysaccharide (LPS)
Mus musculus
Natural Substrates/ Products (Substrates) (protein specific)
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
nicotinamide + alpha-D-5-phosphoribosyl 1-diphosphate
Mus musculus
nicotinamide clearance
nicotinamide mononucleotide + diphosphate
NMN synthesis is rate-limiting step for NAD+ synthesis
-
r
nicotinamide + alpha-D-5-phosphoribosyl 1-diphosphate
Homo sapiens
nicotinamide clearance
nicotinamide mononucleotide + diphosphate
NMN synthesis is rate-limiting step for NAD+ synthesis
-
r
Source Tissue (protein specific)
Source Tissue
Commentary
Organism
Textmining
blood vessel
positive staining in blood vessels from arthritic joints as revealed by immunohistochemistry using rat monoclonal anti-murine NAMPT antibody
Mus musculus
-
chondrocyte
some positive staining in cells of both normal and arthritic joints as revealed by immunohistochemistry using rat monoclonal anti-murine NAMPT antibody
Mus musculus
-
joint
massive expression in synoviocytes of the synovial lining layer, sub-intimal synovium and pannus in joints from mice with type II collagen induced arthritis (CIA) compared to non-arthritic naive DBA/1 mice as revealed by immunohistochemistry using rat monoclonal anti-murine NAMPT antibody, some positive staining in chondrocytes from normal and arthritic joints and in blood vessels and inflammatory cells from arthritic joints
Mus musculus
-
monocyte
isolated from total PBMCs from blood from healthy individuals
Homo sapiens
-
monocyte-derived dendritic cell
from blood from healthy individuals
Homo sapiens
-
paw
elevated levels in mice with type II collagen induced arthritis (CIA) compared to non-arthritic naive DBA/1 mice as revealed by ELISA using a mouse visfatin/PBEF ELISA kit
Mus musculus
-
peripheral blood mononuclear cell
PBMC from blood from healthy individuals
Homo sapiens
-
peritoneal exudate
(PEC) isolated from naive C57BL/6 mice of from lipopolysaccharide-treated mice
Mus musculus
-
serum
elevated levels upon type II collagen induced arthritis (CIA) compared to non-arthritic naive DBA/1 mice as revealed by ELISA using a mouse visfatin/PBEF ELISA kit
Mus musculus
-
Substrates and Products (Substrate) (protein specific)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
nicotinamide + alpha-D-5-phosphoribosyl 1-diphosphate
nicotinamide clearance
694813
Mus musculus
nicotinamide mononucleotide + diphosphate
NMN synthesis is rate-limiting step for NAD+ synthesis
-
-
r
nicotinamide + alpha-D-5-phosphoribosyl 1-diphosphate
nicotinamide clearance
694813
Homo sapiens
nicotinamide mononucleotide + diphosphate
NMN synthesis is rate-limiting step for NAD+ synthesis
-
-
r
Other publictions for EC 2.4.2.12
No.
1st author
Pub Med
title
organims
journal
volume
pages
year
Activating Compound
Application
Cloned(Commentary)
Crystallization (Commentary)
Engineering
General Stability
Inhibitors
KM Value [mM]
Localization
Metals/Ions
Molecular Weight [Da]
Natural Substrates/ Products (Substrates)
Organic Solvent Stability
Organism
Oxidation Stability
Posttranslational Modification
Purification (Commentary)
Reaction
Renatured (Commentary)
Source Tissue
Specific Activity [micromol/min/mg]
Storage Stability
Substrates and Products (Substrate)
Subunits
Temperature Optimum [°C]
Temperature Range [°C]
Temperature Stability [°C]
Turnover Number [1/s]
pH Optimum
pH Range
pH Stability
Cofactor
Ki Value [mM]
pI Value
IC50 Value
Activating Compound (protein specific)
Application (protein specific)
Cloned(Commentary) (protein specific)
Cofactor (protein specific)
Crystallization (Commentary) (protein specific)
Engineering (protein specific)
General Stability (protein specific)
IC50 Value (protein specific)
Inhibitors (protein specific)
Ki Value [mM] (protein specific)
KM Value [mM] (protein specific)
Localization (protein specific)
Metals/Ions (protein specific)
Molecular Weight [Da] (protein specific)
Natural Substrates/ Products (Substrates) (protein specific)
Organic Solvent Stability (protein specific)
Oxidation Stability (protein specific)
Posttranslational Modification (protein specific)
Purification (Commentary) (protein specific)
Renatured (Commentary) (protein specific)
Source Tissue (protein specific)
Specific Activity [micromol/min/mg] (protein specific)
Storage Stability (protein specific)
Substrates and Products (Substrate) (protein specific)
Subunits (protein specific)
Temperature Optimum [°C] (protein specific)
Temperature Range [°C] (protein specific)
Temperature Stability [°C] (protein specific)
Turnover Number [1/s] (protein specific)
pH Optimum (protein specific)
pH Range (protein specific)
pH Stability (protein specific)
pI Value (protein specific)
Expression
General Information
General Information (protein specific)
Expression (protein specific)
KCat/KM [mM/s]
KCat/KM [mM/s] (protein specific)
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1
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Homo sapiens
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49
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2
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4
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1
1
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48
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48
49
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1
1
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4
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1
1
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Homo sapiens, Rattus norvegicus
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144
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-
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14
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6
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2
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Homo sapiens
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24
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2014
-
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18
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1
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18
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Homo sapiens
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23
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2014
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1
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1
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736227
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Homo sapiens, Mus musculus
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92
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3
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735758
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Homo sapiens
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32
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736436
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288
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736612
Zheng
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Homo sapiens
J. Med. Chem.
56
6413-6433
2013
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40
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723576
Bowlby
Nicotinamide phosphoribosyl tr ...
Homo sapiens
PLoS ONE
7
e40195
2012
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723588
Liu
Nicotinamide phosphoribosyltra ...
Mus musculus
PLoS ONE
7
e44933
2012
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721273
Zhang
A fluorometric assay for high- ...
Mus musculus
Anal. Biochem.
412
18-25
2011
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1
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722099
Friebe
Leucocytes are a major source ...
Homo sapiens
Diabetologia
54
1200-1211
2011
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489737
Preiss
Enzymatic synthesis of nicotin ...
Homo sapiens
J. Biol. Chem.
225
759-770
1957
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