Page last updated: 2024-11-05

6-aminonicotinamide

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

6-Aminonicotinamide (6-AN) is a pyridine derivative that acts as a potent inhibitor of nicotinamide adenine dinucleotide (NAD+) biosynthesis. 6-AN has been shown to have various biological effects, including anti-inflammatory, anti-cancer, and neuroprotective activities. It is also a potential therapeutic agent for treating metabolic diseases such as diabetes and obesity. 6-AN inhibits the enzyme nicotinamide phosphoribosyltransferase (NAMPT), which is the rate-limiting enzyme in the salvage pathway of NAD+ biosynthesis. Inhibition of NAMPT leads to a decrease in NAD+ levels, which has been shown to have various biological effects. 6-AN is synthesized through a multi-step process that involves the reaction of nicotinamide with a variety of reagents. 6-AN has been studied extensively for its therapeutic potential in a variety of diseases. Its anti-inflammatory effects are due to its ability to inhibit the production of pro-inflammatory cytokines. 6-AN has also been shown to have anti-cancer activity by inducing apoptosis in cancer cells. In addition, 6-AN has been shown to protect neurons from damage in various models of neurodegenerative diseases. The importance of 6-AN lies in its ability to target NAD+ metabolism, a key pathway involved in various cellular processes. Its potential therapeutic applications in a variety of diseases, including inflammatory, metabolic, and neurodegenerative diseases, make it an important molecule for further research and development.'

6-Aminonicotinamide: A vitamin antagonist which has teratogenic effects. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

6-aminonicotinamide : A monocarboxylic acid amide resulting from the formal condensation of the carboxy group of 6-aminonicotinic acid with ammonia. An inhibitor of the NADP(+)-dependent enzyme, 6-phosphogluconate dehydrogenase, it interferes with glycolysis, resulting in ATP depletion and synergizes with DNA-crosslinking chemotherapy drugs, such as cisplatin, in killing cancer cells. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID9500
CHEMBL ID1324108
CHEBI ID74514
SCHEMBL ID105510
MeSH IDM0023261

Synonyms (80)

Synonym
MLS002207034
smr001306701
AKOS003406190
2-amino-5-carbamoylpyridine
aminonicotinamide
nsc-21206
nsc21206 ,
3-pyridinecarboxamide, 6-amino-
nsc 21206
wln: t6nj bz evz
6-aminonicotinic acid amide
u-8774
6-aminonikotinsaeureamid
6-amino-nicotinsaeureamid
nicotinamide, 6-amino-
329-89-5
6-an
fda 0121
NCIMECH_000769
NCI60_001784
brn 0116042
ccris 7679
sr 4388
ai3-50770
6-aminonikotinsaeureamid [german]
einecs 206-349-7
6-aminopyridine-3-carboxamide
6-aminonitoinamide
6-aminonicotinamide
6-aminonicotinamide, 99%
BSPBIO_003576
NCGC00095299-01
NCGC00095299-02
KBIO3_002955
SPBIO_001698
SPECTRUM2_001709
SPECTRUM3_001976
SPECTRUM1505315
NCGC00095299-03
2-aminopyridine-5-carboxamide
A0986
5-22-13-00618 (beilstein handbook reference)
d6fnw67f2b ,
unii-d6fnw67f2b
CHEMBL1324108
6-amino-3-pyridinecarboxamide
A821549
6-azanylpyridine-3-carboxamide
S9783
CCG-35857
BP-13037
CHEBI:74514 ,
6-ana
FT-0620940
6-amino nicotinamide
6-amino-nicotinamide
SCHEMBL105510
4fg ,
TS-00033
dtxcid4030043
cas-329-89-5
tox21_303956
NCGC00357190-01
dtxsid5051446 ,
W-202353
AC-31893
mfcd00006327
gtc000445a
bdbm225673
BBL104231
STL558250
Q26841298
HMS3865N03
AMY5634
SY038238
EN300-1257643
CS-W011058
HY-W010342
Z959893184
PD000946

Research Excerpts

Dosage Studied

ExcerptRelevanceReference
" Probit analysis of the cleft-palate response to dose of different genotypes revealed a family of linear and parallel dose-response curves."( 6-Aminonicotinamide-induced cleft palate in the mouse: the nature of the difference between the A/J and C57Bl/6J strains in frequency of response and its genetic basis.
Biddle, FG, 1977
)
1.7
"The examples of 6-AN- and cortisone-induced cleft palate in the mouse suggest that dose-response studies can be used to discriminate whether mechanisms of action are different for different teratogens."( Use of dose-response relationships to discriminate between the mechanisms of cleft-palate induction by different teratogens: an argument for discussion.
Biddle, FG, 1978
)
0.26
" A similar study was conducted with Dutch-Belted rabbits dosed po daily at 3, 10, 30, or 100 mg of o-toluenediamine/kg body wt/day from Days 6 through 18 of gestation."( Teratogenesis study of o-toluenediamine in rats and rabbits.
Barbee, SJ; Becci, PJ; Knickerbocker, MJ; Reagan, EL; Wedig, JH, 1983
)
0.27
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (3)

RoleDescription
teratogenic agentA role played by a chemical compound in biological systems with adverse consequences in embryo developments, leading to birth defects, embryo death or altered development, growth retardation and functional defect.
antimetaboliteA substance which is structurally similar to a metabolite but which competes with it or replaces it, and so prevents or reduces its normal utilization.
EC 1.1.1.44 (NADP(+)-dependent decarboxylating phosphogluconate dehydrogenase) inhibitorAn EC 1.1.1.* (oxidoreductase acting on donor CH-OH group, NAD(+) or NADP(+) acceptor) inhibitor that interferes with the action of NADP(+)-dependent decarboxylating phosphogluconate dehydrogenase (EC 1.1.1.44).
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (3)

ClassDescription
aminopyridineCompounds containing a pyridine skeleton substituted by one or more amine groups.
primary amino compoundA compound formally derived from ammonia by replacing one hydrogen atom by an organyl group.
monocarboxylic acid amideA carboxamide derived from a monocarboxylic acid.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (18)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
glp-1 receptor, partialHomo sapiens (human)Potency31.62280.01846.806014.1254AID624417
RAR-related orphan receptor gammaMus musculus (house mouse)Potency0.66200.006038.004119,952.5996AID1159521; AID1159523
TDP1 proteinHomo sapiens (human)Potency3.61490.000811.382244.6684AID686978; AID686979
AR proteinHomo sapiens (human)Potency6.48600.000221.22318,912.5098AID1259243; AID1259247
estrogen receptor 2 (ER beta)Homo sapiens (human)Potency61.13060.000657.913322,387.1992AID1259377
nuclear receptor subfamily 1, group I, member 3Homo sapiens (human)Potency61.13060.001022.650876.6163AID1224839
retinoic acid nuclear receptor alpha variant 1Homo sapiens (human)Potency35.74710.003041.611522,387.1992AID1159552; AID1159555
retinoid X nuclear receptor alphaHomo sapiens (human)Potency13.80060.000817.505159.3239AID1159527
estrogen-related nuclear receptor alphaHomo sapiens (human)Potency21.66330.001530.607315,848.9004AID1224841; AID1224842; AID1224848; AID1224849; AID1259401; AID1259403
estrogen nuclear receptor alphaHomo sapiens (human)Potency68.58960.000229.305416,493.5996AID1259244
IDH1Homo sapiens (human)Potency2.59290.005210.865235.4813AID686970
chromobox protein homolog 1Homo sapiens (human)Potency89.12510.006026.168889.1251AID540317
nuclear factor erythroid 2-related factor 2 isoform 2Homo sapiens (human)Potency20.59620.00419.984825.9290AID504444
gemininHomo sapiens (human)Potency11.08240.004611.374133.4983AID624296; AID624297
survival motor neuron protein isoform dHomo sapiens (human)Potency35.48130.125912.234435.4813AID1458
Voltage-dependent calcium channel gamma-2 subunitMus musculus (house mouse)Potency68.58960.001557.789015,848.9004AID1259244
Glutamate receptor 2Rattus norvegicus (Norway rat)Potency68.58960.001551.739315,848.9004AID1259244
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Nicotinamide N-methyltransferaseHomo sapiens (human)IC50 (µMol)3.62003.62004.41005.2000AID1918421
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (8)

Processvia Protein(s)Taxonomy
nicotinamide metabolic processNicotinamide N-methyltransferaseHomo sapiens (human)
response to xenobiotic stimulusNicotinamide N-methyltransferaseHomo sapiens (human)
response to organonitrogen compoundNicotinamide N-methyltransferaseHomo sapiens (human)
animal organ regenerationNicotinamide N-methyltransferaseHomo sapiens (human)
methylationNicotinamide N-methyltransferaseHomo sapiens (human)
NAD biosynthesis via nicotinamide riboside salvage pathwayNicotinamide N-methyltransferaseHomo sapiens (human)
positive regulation of gluconeogenesisNicotinamide N-methyltransferaseHomo sapiens (human)
positive regulation of protein deacetylationNicotinamide N-methyltransferaseHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (2)

Processvia Protein(s)Taxonomy
nicotinamide N-methyltransferase activityNicotinamide N-methyltransferaseHomo sapiens (human)
pyridine N-methyltransferase activityNicotinamide N-methyltransferaseHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (2)

Processvia Protein(s)Taxonomy
plasma membraneGlutamate receptor 2Rattus norvegicus (Norway rat)
cytosolNicotinamide N-methyltransferaseHomo sapiens (human)
cytosolNicotinamide N-methyltransferaseHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (22)

Assay IDTitleYearJournalArticle
AID1852958Inhibition of 6PGD in human A38-5 cells assessed as increase in Ru-5-P level at 250 uM incubated for 72 hrs by mass spectrometry2022ACS medicinal chemistry letters, Dec-08, Volume: 13, Issue:12
Effects of 6-Aminonicotinic Acid Esters on the Reprogrammed Epigenetic State of Distant Metastatic Pancreatic Carcinoma.
AID977599Inhibition of sodium fluorescein uptake in OATP1B1-transfected CHO cells at an equimolar substrate-inhibitor concentration of 10 uM2013Molecular pharmacology, Jun, Volume: 83, Issue:6
Structure-based identification of OATP1B1/3 inhibitors.
AID977602Inhibition of sodium fluorescein uptake in OATP1B3-transfected CHO cells at an equimolar substrate-inhibitor concentration of 10 uM2013Molecular pharmacology, Jun, Volume: 83, Issue:6
Structure-based identification of OATP1B1/3 inhibitors.
AID1852957Inhibition of G6PD in human A38-5 cells assessed as fold increase in G6P level at 250 uM incubated for 72 hrs by mass spectrometry2022ACS medicinal chemistry letters, Dec-08, Volume: 13, Issue:12
Effects of 6-Aminonicotinic Acid Esters on the Reprogrammed Epigenetic State of Distant Metastatic Pancreatic Carcinoma.
AID1852963Neurotoxicity against Sprague-Dawley rat Primary hippocampal neuron assessed as increase in TUNEL positive cells at 50 uM incubated for 24 hrs by TUNEL staining based microscopy2022ACS medicinal chemistry letters, Dec-08, Volume: 13, Issue:12
Effects of 6-Aminonicotinic Acid Esters on the Reprogrammed Epigenetic State of Distant Metastatic Pancreatic Carcinoma.
AID1852962Neurotoxicity against Sprague-Dawley rat Primary hippocampal neuron assessed as increase in TUNEL positive cells at 5 uM incubated for 24 hrs by TUNEL staining based microscopy2022ACS medicinal chemistry letters, Dec-08, Volume: 13, Issue:12
Effects of 6-Aminonicotinic Acid Esters on the Reprogrammed Epigenetic State of Distant Metastatic Pancreatic Carcinoma.
AID1852950Inhibition of 6PGD in human A38-5 cells assessed as fold increase in intracellular H3K9me3 level at 250 uM incubated for 45 mins by HTRF assay2022ACS medicinal chemistry letters, Dec-08, Volume: 13, Issue:12
Effects of 6-Aminonicotinic Acid Esters on the Reprogrammed Epigenetic State of Distant Metastatic Pancreatic Carcinoma.
AID1852949Inhibition of 6PGD in human A38-5 cells assessed as increase in intracellular H3K9me3 level at 0.1 to 1000 uM incubated for 45 mins by HTRF assay2022ACS medicinal chemistry letters, Dec-08, Volume: 13, Issue:12
Effects of 6-Aminonicotinic Acid Esters on the Reprogrammed Epigenetic State of Distant Metastatic Pancreatic Carcinoma.
AID1918421Inhibition of human NNMT measured after 20 mins by luminescence based methyltransferase assay
AID1852956Inhibition of 6PGD in human A38-5 cells assessed as fold increase in 6PG level at 250 uM incubated for 72 hrs by mass spectrometry2022ACS medicinal chemistry letters, Dec-08, Volume: 13, Issue:12
Effects of 6-Aminonicotinic Acid Esters on the Reprogrammed Epigenetic State of Distant Metastatic Pancreatic Carcinoma.
AID588497High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588497High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588497High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID588501High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588501High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588501High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID588499High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588499High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588499High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID1745845Primary qHTS for Inhibitors of ATXN expression
AID651635Viability Counterscreen for Primary qHTS for Inhibitors of ATXN expression
AID1159550Human Phosphogluconate dehydrogenase (6PGD) Inhibitor Screening2015Nature cell biology, Nov, Volume: 17, Issue:11
6-Phosphogluconate dehydrogenase links oxidative PPP, lipogenesis and tumour growth by inhibiting LKB1-AMPK signalling.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (326)

TimeframeStudies, This Drug (%)All Drugs %
pre-1990194 (59.51)18.7374
1990's51 (15.64)18.2507
2000's39 (11.96)29.6817
2010's34 (10.43)24.3611
2020's8 (2.45)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 27.62

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index27.62 (24.57)
Research Supply Index5.84 (2.92)
Research Growth Index4.30 (4.65)
Search Engine Demand Index35.70 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (27.62)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials1 (0.29%)5.53%
Reviews10 (2.92%)6.00%
Case Studies4 (1.17%)4.05%
Observational0 (0.00%)0.25%
Other327 (95.61%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]