Literature summary for 2.4.2.12 extracted from

Busso, N.; Karababa, M.; Nobile, M.; Rolaz, A.; Van Gool, F.; Galli, M.; Leo, O.; So, A.; De Smedt, T.
Pharmacological inhibition of nicotinamide phosphoribosyltransferase/visfatin enzymatic activity identifies a new inflammatory pathway linked to NAD (2008), PLoS ONE, 3, e2267.

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Application

Application	Comment	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	Comment	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	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
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	UniProt	Comment	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	Comment	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	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
nicotinamide + alpha-D-5-phosphoribosyl 1-diphosphate	nicotinamide clearance	Mus musculus	nicotinamide mononucleotide + diphosphate	NMN synthesis is rate-limiting step for NAD+ synthesis	r
nicotinamide + alpha-D-5-phosphoribosyl 1-diphosphate	nicotinamide clearance	Homo sapiens	nicotinamide mononucleotide + diphosphate	NMN synthesis is rate-limiting step for NAD+ synthesis	r

Synonyms

Synonyms	Comment	Organism
Nampt	-	Mus musculus
Nampt	-	Homo sapiens
nicotinamide phosphoribosyltransferase	-	Mus musculus
nicotinamide phosphoribosyltransferase	-	Homo sapiens
PBEF	-	Mus musculus
PBEF	-	Homo sapiens
pre-B-cell colony-enhancing factor	-	Mus musculus
pre-B-cell colony-enhancing factor	-	Homo sapiens
Visfatin	-	Mus musculus
Visfatin	-	Homo sapiens

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Release 2023.1 (January 2023)