Literature summary for 2.7.11.24 extracted from

Pettus, L.H.; Xu, S.; Cao, G.Q.; Chakrabarti, P.P.; Rzasa, R.M.; Sham, K.; Wurz, R.P.; Zhang, D.; Middleton, S.; Henkle, B.; Plant, M.H.; Saris, C.J.; Sherman, L.; Wong, L.M.; Powers, D.A.; Tudor, Y.; Yu, V.; Lee, M.R.; Syed, R.; Hsieh, F.; Tasker, A.S.
3-amino-7-phthalazinylbenzoisoxazoles as a novel class of potent, selective, and orally available inhibitors of p38alpha mitogen-activated protein kinase (2008), J. Med. Chem., 51, 6280-6292.

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Application

Application	Comment	Organism
drug development	p38 MAPK inhibitors have significant therapeutic potential for the treatment of rheumatoid arthritis, inflammatory bowel disease, osteoporosis, and many other diseases where aberrant cytokine signaling is the driver of disease	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism	Structure
1-((S)-4-(6-(3-(cyclopropylamino)-6-methylbenzo[d]isoxazol-7-yl)phthalazin-1-yl)-3-methylpiperazin-1-yl)ethanone	-	Homo sapiens
6-(3-(cyclopropylamino)-6-methylbenzo[d]isoxazol-7-yl)-N,N-dimethylphthalazin-1-amine	-	Homo sapiens
6-chloro-N-cyclopropyl-7-(1-((S)-3-methylmorpholino)phthalazin-6-yl)benzo[d]isoxazol-3-amine	-	Homo sapiens
6-chloro-N-isopropyl-7-(1-((S)-3-methylmorpholino)phthalazin-6-yl)benzo[d]isoxazol-3-amine	-	Homo sapiens
6-methyl-7-(1-((S)-3-methylmorpholino)phthalazin-6-yl)-1H-indazol-3-amine	-	Homo sapiens
6-methyl-7-(1-((S)-3-methylmorpholino)phthalazin-6-yl)benzo[d]isothiazol-3-amine	-	Homo sapiens
6-methyl-7-(1-((S)-3-methylmorpholino)phthalazin-6-yl)benzo[d]isoxazol-3-amine	-	Homo sapiens
7-(1-isopropoxyphthalazin-6-yl)-N,6-dimethylbenzo[d]isoxazol-3-amine	-	Homo sapiens
7-(1-isopropylphthalazin-6-yl)-N,6-dimethylbenzo[d]isoxazol-3-amine	-	Homo sapiens
additional information	synthesis of 3-amino-7-phthalazinylbenzoisoxazole-based inhibitors, structure-activity realationship, overview	Homo sapiens
N,6-dimethyl-7-(1-((R)-3-methylmorpholino)phthalazin-6-yl)-benzo[d]isoxazol-3-amine	-	Homo sapiens
N,6-dimethyl-7-(1-((S)-3-methylmorpholino)phthalazin-6-yl)-benzo[d]isoxazol-3-amine	-	Homo sapiens
N-(6-methyl-7-(1-((S)-3-methylmorpholino)phthalazin-6-yl)-benzo[d]isoxazol-3-yl)acetamide	-	Homo sapiens
N-(S)-sec-butyl-6-(6-methyl-3-(methylamino)benzo[d]isoxazol-7-yl)phthalazin-1-amine	-	Homo sapiens
N-cyclopropyl-6-methyl-7-(1-((S)-3-methylmorpholino)phthalazin-6-yl)benzo[d]isoxazol-3-amine	-	Homo sapiens
N-cyclopropyl-6-methyl-7-(1-o-tolylphthalazin-6-yl)benzo[d]-isoxazol-3-amine	-	Homo sapiens
N-ethyl-6-methyl-7-(1-((S)-3-methylmorpholino)phthalazin-6-yl)benzo[d]isoxazol-3-amine	-	Homo sapiens
N-isopropyl-6-(6-methyl-3-(methylamino)benzo[d]isoxazol-7-yl)phthalazin-1-amine	-	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
additional information	Homo sapiens	p38 MAPK is a central signaling molecule in many proinflammatory pathways, regulating the cellular response to a multitude of external stimuli including heat, ultraviolet radiation, osmotic shock, and a variety of cytokines especially interleukin-1beta and tumor necrosis factor alpha	?	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	Q16539	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
THP-1 cell	-	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
additional information	p38 MAPK is a central signaling molecule in many proinflammatory pathways, regulating the cellular response to a multitude of external stimuli including heat, ultraviolet radiation, osmotic shock, and a variety of cytokines especially interleukin-1beta and tumor necrosis factor alpha	Homo sapiens	?	-	?

Synonyms

Synonyms	Comment	Organism
p38 MAPK	-	Homo sapiens

Ki Value [mM]

Ki Value [mM]	Ki Value maximum [mM]	Inhibitor	Comment	Organism	Structure
0.0000002	-	6-chloro-N-cyclopropyl-7-(1-((S)-3-methylmorpholino)phthalazin-6-yl)benzo[d]isoxazol-3-amine	inhibition of p38 MAPK	Homo sapiens
0.0000002	-	N-(S)-sec-butyl-6-(6-methyl-3-(methylamino)benzo[d]isoxazol-7-yl)phthalazin-1-amine	inhibition of p38 MAPK	Homo sapiens
0.0000003	-	N-ethyl-6-methyl-7-(1-((S)-3-methylmorpholino)phthalazin-6-yl)benzo[d]isoxazol-3-amine	inhibition of p38 MAPK	Homo sapiens
0.0000003	-	6-methyl-7-(1-((S)-3-methylmorpholino)phthalazin-6-yl)benzo[d]isoxazol-3-amine	inhibition of p38 MAPK	Homo sapiens
0.0000003	-	N,6-dimethyl-7-(1-((R)-3-methylmorpholino)phthalazin-6-yl)-benzo[d]isoxazol-3-amine	inhibition of p38 MAPK	Homo sapiens
0.0000004	-	N-cyclopropyl-6-methyl-7-(1-o-tolylphthalazin-6-yl)benzo[d]-isoxazol-3-amine	inhibition of p38 MAPK	Homo sapiens
0.0000004	-	N,6-dimethyl-7-(1-((S)-3-methylmorpholino)phthalazin-6-yl)-benzo[d]isoxazol-3-amine	inhibition of p38 MAPK	Homo sapiens
0.0000004	-	6-chloro-N-isopropyl-7-(1-((S)-3-methylmorpholino)phthalazin-6-yl)benzo[d]isoxazol-3-amine	inhibition of p38 MAPK	Homo sapiens
0.0000004	-	7-(1-isopropoxyphthalazin-6-yl)-N,6-dimethylbenzo[d]isoxazol-3-amine	inhibition of p38 MAPK	Homo sapiens
0.0000005	-	6-(3-(cyclopropylamino)-6-methylbenzo[d]isoxazol-7-yl)-N,N-dimethylphthalazin-1-amine	inhibition of p38 MAPK	Homo sapiens
0.0000005	-	N-isopropyl-6-(6-methyl-3-(methylamino)benzo[d]isoxazol-7-yl)phthalazin-1-amine	inhibition of p38 MAPK	Homo sapiens
0.0000006	-	N-(6-methyl-7-(1-((S)-3-methylmorpholino)phthalazin-6-yl)-benzo[d]isoxazol-3-yl)acetamide	inhibition of p38 MAPK	Homo sapiens
0.0000007	-	N-cyclopropyl-6-methyl-7-(1-((S)-3-methylmorpholino)phthalazin-6-yl)benzo[d]isoxazol-3-amine	inhibition of p38 MAPK	Homo sapiens
0.0000008	-	1-((S)-4-(6-(3-(cyclopropylamino)-6-methylbenzo[d]isoxazol-7-yl)phthalazin-1-yl)-3-methylpiperazin-1-yl)ethanone	inhibition of p38 MAPK	Homo sapiens
0.0000011	-	7-(1-isopropylphthalazin-6-yl)-N,6-dimethylbenzo[d]isoxazol-3-amine	inhibition of p38 MAPK	Homo sapiens
0.000002	-	6-methyl-7-(1-((S)-3-methylmorpholino)phthalazin-6-yl)benzo[d]isothiazol-3-amine	inhibition of p38 MAPK	Homo sapiens
0.000016	-	6-methyl-7-(1-((S)-3-methylmorpholino)phthalazin-6-yl)-1H-indazol-3-amine	inhibition of p38 MAPK	Homo sapiens

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor	Structure
0.0000004	-	THP-1 cells	Homo sapiens	N-cyclopropyl-6-methyl-7-(1-o-tolylphthalazin-6-yl)benzo[d]-isoxazol-3-amine
0.0000004	-	THP-1 cells	Homo sapiens	N-ethyl-6-methyl-7-(1-((S)-3-methylmorpholino)phthalazin-6-yl)benzo[d]isoxazol-3-amine
0.0000004	-	THP-1 cells	Homo sapiens	N,6-dimethyl-7-(1-((S)-3-methylmorpholino)phthalazin-6-yl)-benzo[d]isoxazol-3-amine
0.0000004	-	THP-1 cells	Homo sapiens	6-(3-(cyclopropylamino)-6-methylbenzo[d]isoxazol-7-yl)-N,N-dimethylphthalazin-1-amine
0.0000006	-	THP-1 cells	Homo sapiens	N-cyclopropyl-6-methyl-7-(1-((S)-3-methylmorpholino)phthalazin-6-yl)benzo[d]isoxazol-3-amine
0.0000007	-	THP-1 cells	Homo sapiens	N-(6-methyl-7-(1-((S)-3-methylmorpholino)phthalazin-6-yl)-benzo[d]isoxazol-3-yl)acetamide
0.0000007	-	THP-1 cells	Homo sapiens	N-isopropyl-6-(6-methyl-3-(methylamino)benzo[d]isoxazol-7-yl)phthalazin-1-amine
0.0000007	-	THP-1 cells	Homo sapiens	7-(1-isopropoxyphthalazin-6-yl)-N,6-dimethylbenzo[d]isoxazol-3-amine
0.0000008	-	THP-1 cells	Homo sapiens	1-((S)-4-(6-(3-(cyclopropylamino)-6-methylbenzo[d]isoxazol-7-yl)phthalazin-1-yl)-3-methylpiperazin-1-yl)ethanone
0.000001	-	THP-1 cells	Homo sapiens	N,6-dimethyl-7-(1-((R)-3-methylmorpholino)phthalazin-6-yl)-benzo[d]isoxazol-3-amine
0.0000011	-	THP-1 cells	Homo sapiens	7-(1-isopropylphthalazin-6-yl)-N,6-dimethylbenzo[d]isoxazol-3-amine
0.0000013	-	THP-1 cells	Homo sapiens	6-chloro-N-cyclopropyl-7-(1-((S)-3-methylmorpholino)phthalazin-6-yl)benzo[d]isoxazol-3-amine
0.0000013	-	THP-1 cells	Homo sapiens	N-(S)-sec-butyl-6-(6-methyl-3-(methylamino)benzo[d]isoxazol-7-yl)phthalazin-1-amine
0.0000036	-	THP-1 cells	Homo sapiens	6-methyl-7-(1-((S)-3-methylmorpholino)phthalazin-6-yl)benzo[d]isoxazol-3-amine
0.0000036	-	THP-1 cells	Homo sapiens	6-chloro-N-isopropyl-7-(1-((S)-3-methylmorpholino)phthalazin-6-yl)benzo[d]isoxazol-3-amine
0.000029	-	THP-1 cells	Homo sapiens	6-methyl-7-(1-((S)-3-methylmorpholino)phthalazin-6-yl)benzo[d]isothiazol-3-amine
0.00012	-	THP-1 cells	Homo sapiens	6-methyl-7-(1-((S)-3-methylmorpholino)phthalazin-6-yl)-1H-indazol-3-amine

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Release 2023.1 (January 2023)