Literature summary for 1.14.11.67 extracted from

Tumber, A.; Nuzzi, A.; Hookway, E.S.; Hatch, S.B.; Velupillai, S.; Johansson, C.; Kawamura, A.; Savitsky, P.; Yapp, C.; Szykowska, A.; Wu, N.; Bountra, C.; Strain-Damerell, C.; Burgess-Brown, N.A.; Ruda, G.F.; Fedorov, O.; Munro, S.; England, K.S.; Nowak, R.P.; Schofield, C.J.; La Thangue, N.B.; Pawlyn, C.
Potent and selective KDM5 inhibitor stops cellular demethylation of H3K4me3 at transcription start sites and proliferation of MM1S myeloma cells (2017), Cell Chem. Biol., 24, 371-380 .

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Crystallization (Commentary)

Crystallization (Comment)	Organism
purified recombinant enzyme in complex with inhibitor KDOAM-25, sitting drop vapor diffusion method, mixing of 50 nl of 8.1 mg/ml protein in solution with 1 mM KDOAM-25 and 4 mM MnCl2, is mixed with ,precipitant solution consisting of 1.6 M Na/K phosphate, and 0.1 M HEPES, pH 7.5, and 20 nL of KDM5B seeds of crystals obtained from the same condition, 4°C, X-ray diffraction structure determination and analysis at 2.0 A resolution, modeling	Homo sapiens

Crystallization (Comment)

Organism

purified recombinant enzyme in complex with inhibitor KDOAM-25, sitting drop vapor diffusion method, mixing of 50 nl of 8.1 mg/ml protein in solution with 1 mM KDOAM-25 and 4 mM MnCl2, is mixed with ,precipitant solution consisting of 1.6 M Na/K phosphate, and 0.1 M HEPES, pH 7.5, and 20 nL of KDM5B seeds of crystals obtained from the same condition, 4°C, X-ray diffraction structure determination and analysis at 2.0 A resolution, modeling

Homo sapiens

Inhibitors

Inhibitors	Comment	Organism
2-(((2-((2-(dimethylamino)ethyl)(ethyl)amino)-2-oxoethyl)amino)methyl)-N-ethylisonicotinamide	-	Homo sapiens
2-(((2-((2-(dimethylamino)ethyl)(ethyl)amino)-2-oxoethyl)amino)methyl)-N-methylisonicotinamide	-	Homo sapiens
2-(((2-((2-(dimethylamino)ethyl)(ethyl)amino)-2-oxoethyl)amino)methyl)isonicotinamide	the potent and selective KDM5A-D inhibitor stops cellular demethylation of H3K4me3 at transcription start sites and proliferation of MM1S myeloma cells; the potent and selective KDM5A-D inhibitor stops cellular demethylation of H3K4me3 at transcription start sites and proliferation of MM1S myeloma cells; the potent and selective KDM5A-D inhibitor stops cellular demethylation of H3K4me3 at transcription start sites and proliferation of MM1S myeloma cells. Analysis of enzyme-inhibitor binding structure from crystal structure analysis, overview	Homo sapiens
2-(((2-((2-(dimethylamino)ethyl)(ethyl)amino)-2-oxoethyl)amino)methyl)isonicotinic acid	-	Homo sapiens
2-(piperazin-1-ylmethyl)isonicotinic acid	the potent and selective KDM5A-D inhibitor stops cellular demethylation of H3K4me3 at transcription start sites and proliferation of MM1S myeloma cells	Homo sapiens
ethyl 2-(((2-((2-(dimethylamino)ethyl)(ethyl)amino)-2-oxoethyl)amino)methyl)isonicotinate	-	Homo sapiens

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
nucleus	-	Homo sapiens	5634	-

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Fe2+	required for catalysis	Homo sapiens
Fe2+	required for acatalysis	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.
histone H3 N6,N6,N6-trimethyl-L-lysine4 + 2-oxoglutarate + O2	Homo sapiens	-	histone H3 N6,N6-dimethyl-L-lysine4 + succinate + formaldehyde + CO2	-	?
histone H3 N6,N6-dimethyl-L-lysine4 + 2-oxoglutarate + O2	Homo sapiens	-	histone H3 N6-methyl-L-lysine4 + succinate + formaldehyde + CO2	-	?
histone H3 N6-dimethyl-L-lysine4 + 2-oxoglutarate + O2	Homo sapiens	-	histone H3 L-lysine4 + succinate + formaldehyde + CO2	-	?
additional information	Homo sapiens	no activity with histone H3 N6-dimethyl-L-lysine4	?	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P29375	-	-
Homo sapiens	P41229	-	-
Homo sapiens	Q9BY66	-	-
Homo sapiens	Q9UGL1	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
HeLa cell	-	Homo sapiens	-
MM1-S cell	-	Homo sapiens	-
myeloma cell	-	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.
histone H3 N6,N6,N6-trimethyl-L-lysine4 + 2-oxoglutarate + O2	-	Homo sapiens	histone H3 N6,N6-dimethyl-L-lysine4 + succinate + formaldehyde + CO2	-	?
histone H3 N6,N6-dimethyl-L-lysine4 + 2-oxoglutarate + O2	-	Homo sapiens	histone H3 N6-methyl-L-lysine4 + succinate + formaldehyde + CO2	-	?
histone H3 N6-dimethyl-L-lysine4 + 2-oxoglutarate + O2	-	Homo sapiens	histone H3 L-lysine4 + succinate + formaldehyde + CO2	-	?
additional information	no activity with histone H3 N6-dimethyl-L-lysine4	Homo sapiens	?	-	?

Synonyms

Synonyms	Comment	Organism
H3K4me3 demethylase	-	Homo sapiens
KDM5A	-	Homo sapiens
KDM5B	-	Homo sapiens
KDM5C	-	Homo sapiens
KDM5D	-	Homo sapiens

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor
0.000007	-	pH and temperature not specified in the publication	Homo sapiens	2-(((2-((2-(dimethylamino)ethyl)(ethyl)amino)-2-oxoethyl)amino)methyl)isonicotinic acid
0.000019	-	pH and temperature not specified in the publication	Homo sapiens	2-(((2-((2-(dimethylamino)ethyl)(ethyl)amino)-2-oxoethyl)amino)methyl)isonicotinamide
0.000048	-	pH and temperature not specified in the publication	Homo sapiens	ethyl 2-(((2-((2-(dimethylamino)ethyl)(ethyl)amino)-2-oxoethyl)amino)methyl)isonicotinate
0.000069	-	pH and temperature not specified in the publication	Homo sapiens	2-(((2-((2-(dimethylamino)ethyl)(ethyl)amino)-2-oxoethyl)amino)methyl)isonicotinamide
0.000071	-	pH and temperature not specified in the publication	Homo sapiens	2-(((2-((2-(dimethylamino)ethyl)(ethyl)amino)-2-oxoethyl)amino)methyl)isonicotinamide
0.000098	-	pH and temperature not specified in the publication	Homo sapiens	2-(((2-((2-(dimethylamino)ethyl)(ethyl)amino)-2-oxoethyl)amino)methyl)-N-ethylisonicotinamide
0.00027	-	pH and temperature not specified in the publication	Homo sapiens	2-(((2-((2-(dimethylamino)ethyl)(ethyl)amino)-2-oxoethyl)amino)methyl)-N-methylisonicotinamide
0.00098	-	pH and temperature not specified in the publication	Homo sapiens	2-(piperazin-1-ylmethyl)isonicotinic acid

General Information

General Information	Comment	Organism
malfunction	multiple myeloma MM1S cells treated with inhibitor 2-(((2-((2-(dimethylamino)ethyl)(ethyl)amino)-2-oxoethyl)amino)methyl)isonicotinamide show increased global H3K4 methylation at transcriptional start sites and impaired proliferation. Inhibitor 2-(((2-((2-(dimethylamino)ethyl)(ethyl)amino)-2-oxoethyl)amino)methyl)isonicotinamide increases H3K4me3 levels in HeLa cells	Homo sapiens
malfunction	multiple myeloma MM1S cells treated with inhibitor KDOAM-25 show increased global H3K4 methylation at transcriptional start sites and impaired proliferation. Inhibitor KDOAM-25 increases H3K4me3 levels in HeLa cells	Homo sapiens
malfunction	multiple myeloma MM1S cells treated with inhibitor KDOAM-25 show increased global H3K4 methylation at transcriptional start sites and impaired proliferation. Inhibitor KDOAM-25 increases H3K4me3 levels in HeLa cells. Increased KDM5B expression is associated with shorter survival in myeloma patients and ex vivo inhibition with KDOAM-25 results in cell-cycle arrest	Homo sapiens