Literature summary for 2.7.1.40 extracted from

Yacovan, A.; Ozeri, R.; Kehat, T.; Mirilashvili, S.; Sherman, D.; Aizikovich, A.; Shitrit, A.; Ben-Zeev, E.; Schutz, N.; Bohana-Kashtan, O.; Konson, A.; Behar, V.; Becker, O.M.
1-(sulfonyl)-5-(arylsulfonyl)indoline as activators of the tumor cell specific M2 isoform of pyruvate kinase (2012), Bioorg. Med. Chem. Lett., 22, 6460-6468.

Activating Compound

Activating Compound	Comment	Organism
1-[1-(ethylsulfonyl)-2,3-dihydro-1H-indol-5-yl]-2-[(4-methoxyphenyl)sulfanyl]ethanone	-	Homo sapiens
2,3-dihydro-1,4-benzodioxin-6-yl[2-methyl-1-(methylsulfonyl)-2,3-dihydro-1H-indol-5-yl]methanone	-	Homo sapiens
2,6-difluorophenyl 5-(2,3-dihydro-1,4-benzodioxin-6-ylsulfonyl)-2-methyl-2,3-dihydro-1H-indole-1-sulfonate	-	Homo sapiens
2-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)thio)-1-(2-methyl-1-(methylsulfonyl)indolin-5-yl) ethanone	-	Homo sapiens
2-(2,3-dihydro-1,4-benzodioxin-6-ylsulfanyl)-1-[2-methyl-1-(methylsulfonyl)-2,3-dihydro-1H-indol-5-yl]ethanone	-	Homo sapiens
2-(3,4-dihydro-2H-1,5-benzodioxepin-7-ylsulfanyl)-1-[1-(ethylsulfonyl)-2,3-dihydro-1H-indol-5-yl]ethanone	-	Homo sapiens
2-[(3,5-difluorophenyl)sulfanyl]-1-[1-(ethylsulfonyl)-2,3-dihydro-1H-indol-5-yl]ethanone	-	Homo sapiens
3-fluorophenyl 5-(2,3-dihydro-1,4-benzodioxin-6-ylsulfonyl)-2,3-dihydro-1H-indene-1-sulfonate	-	Homo sapiens
3-methoxyphenyl 5-(2,3-dihydro-1,4-benzodioxin-6-ylsulfonyl)-2-methyl-2,3-dihydro-1H-indole-1-sulfonate	-	Homo sapiens
4-fluorophenyl 5-(2,3-dihydro-1,4-benzodioxin-6-ylsulfonyl)-2-methyl-2,3-dihydro-1H-indole-1-sulfonate	-	Homo sapiens
5-(2,3-dihydro-1,4-benzodioxin-6-ylsulfonyl)-1-(methylsulfonyl)-1H-indole	-	Homo sapiens
5-(2,3-dihydro-1,4-benzodioxin-6-ylsulfonyl)-2-methyl-1-(methylsulfonyl)-2,3-dihydro-1H-indole	-	Homo sapiens
5-(2,3-dihydro-1,4-benzodioxin-6-ylsulfonyl)-2-methyl-1-(phenylsulfonyl)-2,3-dihydro-1H-indole	-	Homo sapiens
5-(2,3-dihydro-1,4-benzodioxin-6-ylsulfonyl)-3-methyl-1-(methylsulfonyl)-1H-indole	-	Homo sapiens
6-(2,3-dihydro-1,4-benzodioxin-6-ylsulfonyl)-1-(methylsulfonyl)-1,2,3,4-tetrahydroquinoline	-	Homo sapiens
6-{hydroxy[1-(methylsulfonyl)-1,2,3,7a-tetrahydro-5H-inden-5-ylidene]oxido-l6-sulfanyl}-2,3-dihydro-1,4-benzodioxine	-	Homo sapiens
6-{[1-(cyclopropylsulfonyl)-2,3-dihydro-1H-inden-5-yl]sulfonyl}-2,3-dihydro-1,4-benzodioxine	-	Homo sapiens
6-{[1-(ethylsulfonyl)-2,3-dihydro-1H-inden-5-yl]sulfonyl}-2,3-dihydro-1,4-benzodioxine	-	Homo sapiens
6-{[1-(methylsulfonyl)-2,3-dihydro-1H-inden-5-yl]sulfonyl}-2,3-dihydro-1,4-benzodioxine	-	Homo sapiens
6-{[1-(phenylsulfonyl)-2,3-dihydro-1H-inden-5-yl]sulfonyl}-2,3-dihydro-1,4-benzodioxine	-	Homo sapiens
6-{[2-(ethylsulfonyl)-2,3-dihydro-1H-inden-5-yl]sulfonyl}-2,3-dihydro-1,4-benzodioxine	-	Homo sapiens
6-{[2-(methylsulfonyl)-2,3-dihydro-1H-inden-5-yl]sulfonyl}-2,3-dihydro-1,4-benzodioxine	-	Homo sapiens
6-{[2-(phenylsulfonyl)-2,3-dihydro-1H-inden-5-yl]sulfonyl}-2,3-dihydro-1,4-benzodioxine	-	Homo sapiens
6-{[2-(tert-butylsulfonyl)-2,3-dihydro-1H-inden-5-yl]sulfonyl}-2,3-dihydro-1,4-benzodioxine	-	Homo sapiens
additional information	1-(sulfonyl)-5-(arylsulfonyl)indoline as activators of the tumor cell specific M2 isoform of pyruvate kinase, synthesis, structure-activity relationship analysis, enzyme active site docking, enzymatic reaction kinetics, selectivity, and pharmaceutical properties, overview. Activating potencies of the compounds compared for isozymes PKM2 and PKM1	Homo sapiens
N-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-methyl-1-(methylsulfonyl)-2,3-dihydro-1H-indole-5-sulfonamide	-	Homo sapiens
N-[2-methyl-1-(methylsulfonyl)-2,3-dihydro-1H-indol-5-yl]-2,3-dihydro-1,4-benzodioxine-6-sulfonamide	-	Homo sapiens
N-[4-(2,3-dihydro-1,4-benzodioxin-6-ylsulfonyl)-3-methylphenyl]-N-ethylmethanesulfonamide	-	Homo sapiens
N-[4-(2,3-dihydro-1,4-benzodioxin-6-ylsulfonyl)phenyl]-N-(propan-2-yl)methanesulfonamide	-	Homo sapiens
N-[4-(2,3-dihydro-1,4-benzodioxin-6-ylsulfonyl)phenyl]-N-ethylmethanesulfonamide	-	Homo sapiens
N-{4-[(2,3-dihydro-1,4-benzodioxin-6-ylsulfanyl)acetyl]phenyl}methanesulfonamide	-	Homo sapiens
phenyl 5-(2,3-dihydro-1,4-benzodioxin-6-ylsulfonyl)-2-methyl-2,3-dihydro-1H-indole-1-sulfonate	-	Homo sapiens

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Mg2+	required	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
ATP + pyruvate	Homo sapiens	-	ADP + phosphoenolpyruvate	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	-	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
additional information	prevalence of PKM2 in cancer cells relative to the prevalence of PKM1 in many norma cells	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
ATP + pyruvate	-	Homo sapiens	ADP + phosphoenolpyruvate	-	?

Synonyms

Synonyms	Comment	Organism
PKM1	-	Homo sapiens
PKM2	-	Homo sapiens

Cofactor

Cofactor	Comment	Organism	Structure
ATP	-	Homo sapiens

General Information

General Information	Comment	Organism
physiological function	the Warburg effect, a metabolic change, originates from a shift in the expression of alternative spliced isoforms of the glycolytic enzyme pyruvate kinase, from PKM1 to PKM2. While PKM1 is constitutively active, PKM2 is switched from an inactive dimer form to an active tetramer form by small molecule activators. Activation of PKM2 may counter the abnormal cellular metabolism in cancer cells, and consequently decreased cellular proliferation	Homo sapiens