Page last updated: 2024-11-13

n2-(1h-indazole-5-yl)-n6-methyl-3-nitropyridine-2,6-diamine

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Description

N2-(1H-indazole-5-yl)-N6-methyl-3-nitropyridine-2,6-diamine: a heat shock factor 1 antagonist; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

KRIBB11 : A member of the class of indazoles that is 1H-indazole substituted by a [6-(methylamino)-3-nitropyridin-2-yl]amino group at position 5. It is an inhibitor of heat shock factor 1 (IC50 = 1.2muM) and suppresses tumour growth in mouse xenograft models. [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 CID69894253
CHEMBL ID3609826
SCHEMBL ID6783318
MeSH IDM0555001

Synonyms (24)

Synonym
S8402
SCHEMBL6783318
kribb11
n2-(1h-indazole-5-yl)-n6-methyl-3-nitropyridine-2,6-diamine
AKOS025147370
n2-1h-indazol-5-yl-n6-methyl-3-nitro-2,6-pyridinediamine
342639-96-7
AC-33013
CHEMBL3609826 ,
n2-(1h-indazol-5-yl)-n6-methyl-3-nitropyridine-2,6-diamine
CS-6111
HY-100872
bdbm50114871
NCGC00387499-01
BCP19297
kribb-11;kribb 11
F20670
EX-A2457
mfcd30182306
BS-16921
CCG-267300
A918600
2-(1h-5-indazolylamino)-6-methylamino-3-nitropyridine
2-n-(1h-indazol-5-yl)-6-n-methyl-3-nitropyridine-2,6-diamine

Research Excerpts

Bioavailability

ExcerptReferenceRelevance
"The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs."( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019
)
0.51
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (8)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
cytochrome P450 family 3 subfamily A polypeptide 4Homo sapiens (human)Potency2.13170.01237.983543.2770AID1645841
GVesicular stomatitis virusPotency0.75640.01238.964839.8107AID1645842
cytochrome P450 2D6Homo sapiens (human)Potency4.77240.00108.379861.1304AID1645840
Interferon betaHomo sapiens (human)Potency0.75640.00339.158239.8107AID1645842
HLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)Potency0.75640.01238.964839.8107AID1645842
Inositol hexakisphosphate kinase 1Homo sapiens (human)Potency0.75640.01238.964839.8107AID1645842
cytochrome P450 2C9, partialHomo sapiens (human)Potency0.75640.01238.964839.8107AID1645842
[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)
Heat shock factor protein 1Homo sapiens (human)IC50 (µMol)1.20000.00700.60351.2000AID1242159
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (88)

Processvia Protein(s)Taxonomy
cell surface receptor signaling pathway via JAK-STATInterferon betaHomo sapiens (human)
response to exogenous dsRNAInterferon betaHomo sapiens (human)
B cell activation involved in immune responseInterferon betaHomo sapiens (human)
cell surface receptor signaling pathwayInterferon betaHomo sapiens (human)
cell surface receptor signaling pathway via JAK-STATInterferon betaHomo sapiens (human)
response to virusInterferon betaHomo sapiens (human)
positive regulation of autophagyInterferon betaHomo sapiens (human)
cytokine-mediated signaling pathwayInterferon betaHomo sapiens (human)
natural killer cell activationInterferon betaHomo sapiens (human)
positive regulation of peptidyl-serine phosphorylation of STAT proteinInterferon betaHomo sapiens (human)
cellular response to interferon-betaInterferon betaHomo sapiens (human)
B cell proliferationInterferon betaHomo sapiens (human)
negative regulation of viral genome replicationInterferon betaHomo sapiens (human)
innate immune responseInterferon betaHomo sapiens (human)
positive regulation of innate immune responseInterferon betaHomo sapiens (human)
regulation of MHC class I biosynthetic processInterferon betaHomo sapiens (human)
negative regulation of T cell differentiationInterferon betaHomo sapiens (human)
positive regulation of transcription by RNA polymerase IIInterferon betaHomo sapiens (human)
defense response to virusInterferon betaHomo sapiens (human)
type I interferon-mediated signaling pathwayInterferon betaHomo sapiens (human)
neuron cellular homeostasisInterferon betaHomo sapiens (human)
cellular response to exogenous dsRNAInterferon betaHomo sapiens (human)
cellular response to virusInterferon betaHomo sapiens (human)
negative regulation of Lewy body formationInterferon betaHomo sapiens (human)
negative regulation of T-helper 2 cell cytokine productionInterferon betaHomo sapiens (human)
positive regulation of apoptotic signaling pathwayInterferon betaHomo sapiens (human)
response to exogenous dsRNAInterferon betaHomo sapiens (human)
B cell differentiationInterferon betaHomo sapiens (human)
natural killer cell activation involved in immune responseInterferon betaHomo sapiens (human)
adaptive immune responseInterferon betaHomo sapiens (human)
T cell activation involved in immune responseInterferon betaHomo sapiens (human)
humoral immune responseInterferon betaHomo sapiens (human)
positive regulation of T cell mediated cytotoxicityHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
adaptive immune responseHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independentHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
regulation of T cell anergyHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
defense responseHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
immune responseHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
detection of bacteriumHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
regulation of interleukin-12 productionHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
regulation of interleukin-6 productionHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
protection from natural killer cell mediated cytotoxicityHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
innate immune responseHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
regulation of dendritic cell differentiationHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
antigen processing and presentation of endogenous peptide antigen via MHC class IbHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
positive regulation of transcription by RNA polymerase IIHeat shock factor protein 1Homo sapiens (human)
negative regulation of transcription by RNA polymerase IIHeat shock factor protein 1Homo sapiens (human)
MAPK cascadeHeat shock factor protein 1Homo sapiens (human)
DNA repairHeat shock factor protein 1Homo sapiens (human)
regulation of transcription by RNA polymerase IIHeat shock factor protein 1Homo sapiens (human)
mRNA processingHeat shock factor protein 1Homo sapiens (human)
defense responseHeat shock factor protein 1Homo sapiens (human)
response to nutrientHeat shock factor protein 1Homo sapiens (human)
positive regulation of gene expressionHeat shock factor protein 1Homo sapiens (human)
negative regulation of gene expressionHeat shock factor protein 1Homo sapiens (human)
negative regulation of cardiac muscle cell apoptotic processHeat shock factor protein 1Homo sapiens (human)
response to activityHeat shock factor protein 1Homo sapiens (human)
negative regulation of protein-containing complex assemblyHeat shock factor protein 1Homo sapiens (human)
response to testosteroneHeat shock factor protein 1Homo sapiens (human)
cellular response to heatHeat shock factor protein 1Homo sapiens (human)
cellular response to unfolded proteinHeat shock factor protein 1Homo sapiens (human)
cellular response to potassium ionHeat shock factor protein 1Homo sapiens (human)
positive regulation of tyrosine phosphorylation of STAT proteinHeat shock factor protein 1Homo sapiens (human)
positive regulation of macrophage differentiationHeat shock factor protein 1Homo sapiens (human)
positive regulation of mitotic cell cycleHeat shock factor protein 1Homo sapiens (human)
positive regulation of transcription by RNA polymerase IIHeat shock factor protein 1Homo sapiens (human)
mRNA transportHeat shock factor protein 1Homo sapiens (human)
positive regulation of DNA-binding transcription factor activityHeat shock factor protein 1Homo sapiens (human)
positive regulation of stress granule assemblyHeat shock factor protein 1Homo sapiens (human)
protein-containing complex assemblyHeat shock factor protein 1Homo sapiens (human)
cellular response to hydrogen peroxideHeat shock factor protein 1Homo sapiens (human)
cellular response to lipopolysaccharideHeat shock factor protein 1Homo sapiens (human)
cellular response to cadmium ionHeat shock factor protein 1Homo sapiens (human)
cellular response to copper ionHeat shock factor protein 1Homo sapiens (human)
cellular response to estradiol stimulusHeat shock factor protein 1Homo sapiens (human)
cellular response to xenobiotic stimulusHeat shock factor protein 1Homo sapiens (human)
cellular response to gamma radiationHeat shock factor protein 1Homo sapiens (human)
cellular response to diamideHeat shock factor protein 1Homo sapiens (human)
negative regulation of inclusion body assemblyHeat shock factor protein 1Homo sapiens (human)
positive regulation of inclusion body assemblyHeat shock factor protein 1Homo sapiens (human)
positive regulation of cold-induced thermogenesisHeat shock factor protein 1Homo sapiens (human)
regulation of cellular response to heatHeat shock factor protein 1Homo sapiens (human)
response to peptideHeat shock factor protein 1Homo sapiens (human)
positive regulation of apoptotic DNA fragmentationHeat shock factor protein 1Homo sapiens (human)
cellular response to sodium arseniteHeat shock factor protein 1Homo sapiens (human)
cellular response to angiotensinHeat shock factor protein 1Homo sapiens (human)
cellular response to nitroglycerinHeat shock factor protein 1Homo sapiens (human)
cellular response to L-glutamineHeat shock factor protein 1Homo sapiens (human)
response to hypobaric hypoxiaHeat shock factor protein 1Homo sapiens (human)
response to psychosocial stressHeat shock factor protein 1Homo sapiens (human)
negative regulation of double-strand break repair via nonhomologous end joiningHeat shock factor protein 1Homo sapiens (human)
inositol phosphate metabolic processInositol hexakisphosphate kinase 1Homo sapiens (human)
phosphatidylinositol phosphate biosynthetic processInositol hexakisphosphate kinase 1Homo sapiens (human)
negative regulation of cold-induced thermogenesisInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol phosphate biosynthetic processInositol hexakisphosphate kinase 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (39)

Processvia Protein(s)Taxonomy
cytokine activityInterferon betaHomo sapiens (human)
cytokine receptor bindingInterferon betaHomo sapiens (human)
type I interferon receptor bindingInterferon betaHomo sapiens (human)
protein bindingInterferon betaHomo sapiens (human)
chloramphenicol O-acetyltransferase activityInterferon betaHomo sapiens (human)
TAP bindingHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
signaling receptor bindingHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
protein bindingHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
peptide antigen bindingHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
TAP bindingHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
protein-folding chaperone bindingHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
transcription cis-regulatory region bindingHeat shock factor protein 1Homo sapiens (human)
RNA polymerase II cis-regulatory region sequence-specific DNA bindingHeat shock factor protein 1Homo sapiens (human)
DNA-binding transcription factor activity, RNA polymerase II-specificHeat shock factor protein 1Homo sapiens (human)
RNA polymerase II intronic transcription regulatory region sequence-specific DNA bindingHeat shock factor protein 1Homo sapiens (human)
DNA-binding transcription repressor activity, RNA polymerase II-specificHeat shock factor protein 1Homo sapiens (human)
DNA-binding transcription activator activity, RNA polymerase II-specificHeat shock factor protein 1Homo sapiens (human)
DNA bindingHeat shock factor protein 1Homo sapiens (human)
protein bindingHeat shock factor protein 1Homo sapiens (human)
protein kinase bindingHeat shock factor protein 1Homo sapiens (human)
heat shock protein bindingHeat shock factor protein 1Homo sapiens (human)
chromatin DNA bindingHeat shock factor protein 1Homo sapiens (human)
identical protein bindingHeat shock factor protein 1Homo sapiens (human)
sequence-specific DNA bindingHeat shock factor protein 1Homo sapiens (human)
protein heterodimerization activityHeat shock factor protein 1Homo sapiens (human)
Hsp90 protein bindingHeat shock factor protein 1Homo sapiens (human)
translation elongation factor bindingHeat shock factor protein 1Homo sapiens (human)
STAT family protein bindingHeat shock factor protein 1Homo sapiens (human)
sequence-specific single stranded DNA bindingHeat shock factor protein 1Homo sapiens (human)
general transcription initiation factor bindingHeat shock factor protein 1Homo sapiens (human)
sequence-specific double-stranded DNA bindingHeat shock factor protein 1Homo sapiens (human)
promoter-specific chromatin bindingHeat shock factor protein 1Homo sapiens (human)
DNA-binding transcription factor activityHeat shock factor protein 1Homo sapiens (human)
inositol-1,3,4,5,6-pentakisphosphate kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol hexakisphosphate kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol heptakisphosphate kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol hexakisphosphate 5-kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
protein bindingInositol hexakisphosphate kinase 1Homo sapiens (human)
ATP bindingInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol hexakisphosphate 1-kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol hexakisphosphate 3-kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol 5-diphosphate pentakisphosphate 5-kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol diphosphate tetrakisphosphate kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (33)

Processvia Protein(s)Taxonomy
extracellular spaceInterferon betaHomo sapiens (human)
extracellular regionInterferon betaHomo sapiens (human)
Golgi membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
endoplasmic reticulumHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
Golgi apparatusHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
plasma membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
cell surfaceHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
ER to Golgi transport vesicle membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
secretory granule membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
phagocytic vesicle membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
early endosome membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
recycling endosome membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
extracellular exosomeHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
lumenal side of endoplasmic reticulum membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
MHC class I protein complexHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
extracellular spaceHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
external side of plasma membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
kinetochoreHeat shock factor protein 1Homo sapiens (human)
nucleusHeat shock factor protein 1Homo sapiens (human)
nucleoplasmHeat shock factor protein 1Homo sapiens (human)
cytoplasmHeat shock factor protein 1Homo sapiens (human)
centrosomeHeat shock factor protein 1Homo sapiens (human)
cytosolHeat shock factor protein 1Homo sapiens (human)
PML bodyHeat shock factor protein 1Homo sapiens (human)
perinuclear region of cytoplasmHeat shock factor protein 1Homo sapiens (human)
nuclear stress granuleHeat shock factor protein 1Homo sapiens (human)
mitotic spindle poleHeat shock factor protein 1Homo sapiens (human)
chromatinHeat shock factor protein 1Homo sapiens (human)
euchromatinHeat shock factor protein 1Homo sapiens (human)
heterochromatinHeat shock factor protein 1Homo sapiens (human)
protein folding chaperone complexHeat shock factor protein 1Homo sapiens (human)
ribonucleoprotein complexHeat shock factor protein 1Homo sapiens (human)
nucleusHeat shock factor protein 1Homo sapiens (human)
fibrillar centerInositol hexakisphosphate kinase 1Homo sapiens (human)
nucleoplasmInositol hexakisphosphate kinase 1Homo sapiens (human)
cytosolInositol hexakisphosphate kinase 1Homo sapiens (human)
nucleusInositol hexakisphosphate kinase 1Homo sapiens (human)
cytoplasmInositol hexakisphosphate kinase 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (7)

Assay IDTitleYearJournalArticle
AID1296008Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening2020SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1
Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening.
AID1347160Primary screen NINDS Rhodamine qHTS for Zika virus inhibitors2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1346987P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1347159Primary screen GU Rhodamine qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1346986P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1242159Inhibition of HSF1 (unknown origin) assessed as reduction in HSF1--mediated HSP transcription2015Bioorganic & medicinal chemistry letters, Sep-01, Volume: 25, Issue:17
Regulating the master regulator: Controlling heat shock factor 1 as a chemotherapy approach.
AID1242160Antitumor activity against human HCT116 cells xenografted in mouse assessed as reduction in tumor size at 50 mg/kg2015Bioorganic & medicinal chemistry letters, Sep-01, Volume: 25, Issue:17
Regulating the master regulator: Controlling heat shock factor 1 as a chemotherapy approach.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (14)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's0 (0.00)29.6817
2010's8 (57.14)24.3611
2020's6 (42.86)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 11.93

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 weak demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index11.93 (24.57)
Research Supply Index2.71 (2.92)
Research Growth Index4.64 (4.65)
Search Engine Demand Index0.00 (26.88)
Search Engine Supply Index0.00 (0.95)

This Compound (11.93)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews1 (7.14%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other13 (92.86%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]