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Literature summary for 2.7.11.22 extracted from

  • Woodard, C.L.; Li, Z.; Kathcart, A.K.; Terrell, J.; Gerena, L.; Lopez-Sanchez, M.; Kyle, D.E.; Bhattacharjee, A.K.; Nichols, D.A.; Ellis, W.; Prigge, S.T.; Geyer, J.A.; Waters, N.C.
    Oxindole-based compounds are selective inhibitors of Plasmodium falciparum cyclin dependent protein kinases (2003), J. Med. Chem., 46, 3877-3882.
    View publication on PubMed
Search for more literature for 2.7.11.22

Application

Application Comment Organism
pharmacology the enzyme is a target for drug development in human malaria treatment Homo sapiens
pharmacology the enzyme is a target for drug development in human malaria treatment Plasmodium falciparum

Cloned(Commentary)

Cloned (Comment) Organism
expression of His6-tagged mrk and His6-tagged PK5 in Escherichia coli, co-expression with GST-tagged cyclin-1 Plasmodium falciparum

Inhibitors

Inhibitors Comment Organism Structure
(3Z)-3-(2-oxo-2-phenylethylidene)-1,3-dihydro-2H-indol-2-one IC50 for CDK1 is above 0.016 mM Homo sapiens
(3Z)-3-(2-oxo-2-phenylethylidene)-1,3-dihydro-2H-indol-2-one IC50 for mrk is 0.0040 mM, and for PK5 0.15 mM, only weak inhibition of parasite strains D6 and W2 growth Plasmodium falciparum
(3Z)-3-[2-(4-bromophenyl)-2-oxoethylidene]-1,3-dihydro-2H-indol-2-one IC50 for CDK1 is 0.012 mM Homo sapiens
(3Z)-3-[2-(4-bromophenyl)-2-oxoethylidene]-1,3-dihydro-2H-indol-2-one IC50 for mrk is 0.0035 mM, and for PK5 0.13 mM, only weak inhibition of parasite strains D6 and W2 growth Plasmodium falciparum
(3Z)-5-bromo-3-(2-oxo-2-phenylethylidene)-1,3-dihydro-2H-indol-2-one IC50 for CDK1 is 0.030 mM Homo sapiens
(3Z)-5-bromo-3-(2-oxo-2-phenylethylidene)-1,3-dihydro-2H-indol-2-one IC50 for mrk is 0.0031 mM, and for PK5 0.12 mM, only weak inhibition of parasite strains D6 and W2 growth Plasmodium falciparum
(3Z)-5-bromo-3-[2-(4-fluorophenyl)-2-oxoethylidene]-1,3-dihydro-2H-indol-2-one IC50 for CDK1 is 0.029 mM Homo sapiens
(3Z)-5-bromo-3-[2-(4-fluorophenyl)-2-oxoethylidene]-1,3-dihydro-2H-indol-2-one IC50 for mrk is 0.0014 mM, and for PK5 0.19 mM, only weak inhibition of parasite strains D6 and W2 growth Plasmodium falciparum
(3Z)-5-bromo-3-[2-(4-methylphenyl)-2-oxoethylidene]-1,3-dihydro-2H-indol-2-one IC50 for CDK1 is 0.029 mM Homo sapiens
(3Z)-5-bromo-3-[2-(4-methylphenyl)-2-oxoethylidene]-1,3-dihydro-2H-indol-2-one IC50 for mrk is 0.0029 mM, and for PK5 0.12 mM, only weak inhibition of parasite strains D6 and W2 growth Plasmodium falciparum
additional information molecular modeling of inhibitor-enzyme interactions Plasmodium falciparum
oxindole-based compounds highly selective for mrk, IC50 of mrk is 0.0015 mM, low cross-reactivity with PK5 and human CDK1 Plasmodium falciparum

Metals/Ions

Metals/Ions Comment Organism Structure
Mn2+
-
 Homo sapiens
Mn2+
-
 Plasmodium falciparum

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-
Plasmodium falciparum
-
 strains D6 and W2
-

Purification (Commentary)

Purification (Comment) Organism
recombinant His6-tagged mrk, His6-tagged PK5, and GST-tagged cyclin-1 from Escherichia coli Plasmodium falciparum

Reaction

Reaction Comment Organism Reaction ID
ATP + a [protein]-(L-serine/L-threonine) = ADP + a [protein]-(L-serine/L-threonine) phosphate active site amino acid sequences of PK5 and mrk Plasmodium falciparum
a

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + C-terminal domain of RNA polymerase II
-
 Homo sapiens ADP + phosphorylated C-terminal domain of RNA polymerase II
-
 ?
ATP + C-terminal domain of RNA polymerase II
-
 Plasmodium falciparum ADP + phosphorylated C-terminal domain of RNA polymerase II
-
 ?

Synonyms

Synonyms Comment Organism
CDK
-
 Plasmodium falciparum
Cdk1
-
 Homo sapiens
mrk
-
 Plasmodium falciparum
PK5
-
 Plasmodium falciparum

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
30
-
 assay at Homo sapiens
30
-
 assay at Plasmodium falciparum

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
 assay at Homo sapiens
7.5
-
 assay at Plasmodium falciparum

Cofactor

Cofactor Comment Organism Structure
ATP
-
 Homo sapiens
ATP
-
 Plasmodium falciparum
cyclin-1 regulatory subunit Plasmodium falciparum

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.0014
-
 IC50 for mrk is 0.0014 mM, and for PK5 0.19 mM, only weak inhibition of parasite strains D6 and W2 growth Plasmodium falciparum (3Z)-5-bromo-3-[2-(4-fluorophenyl)-2-oxoethylidene]-1,3-dihydro-2H-indol-2-one
0.0015
-
 highly selective for mrk, IC50 of mrk is 0.0015 mM, low cross-reactivity with PK5 and human CDK1 Plasmodium falciparum oxindole-based compounds
0.0029
-
 IC50 for mrk is 0.0029 mM, and for PK5 0.12 mM, only weak inhibition of parasite strains D6 and W2 growth Plasmodium falciparum (3Z)-5-bromo-3-[2-(4-methylphenyl)-2-oxoethylidene]-1,3-dihydro-2H-indol-2-one
0.0031
-
 IC50 for mrk is 0.0031 mM, and for PK5 0.12 mM, only weak inhibition of parasite strains D6 and W2 growth Plasmodium falciparum (3Z)-5-bromo-3-(2-oxo-2-phenylethylidene)-1,3-dihydro-2H-indol-2-one
0.0035
-
 IC50 for mrk is 0.0035 mM, and for PK5 0.13 mM, only weak inhibition of parasite strains D6 and W2 growth Plasmodium falciparum (3Z)-3-[2-(4-bromophenyl)-2-oxoethylidene]-1,3-dihydro-2H-indol-2-one
0.004
-
 IC50 for mrk is 0.0040 mM, and for PK5 0.15 mM, only weak inhibition of parasite strains D6 and W2 growth Plasmodium falciparum (3Z)-3-(2-oxo-2-phenylethylidene)-1,3-dihydro-2H-indol-2-one
0.012
-
 IC50 for CDK1 is 0.012 mM Homo sapiens (3Z)-3-[2-(4-bromophenyl)-2-oxoethylidene]-1,3-dihydro-2H-indol-2-one
0.016
-
 IC50 for CDK1 is above 0.016 mM Homo sapiens (3Z)-3-(2-oxo-2-phenylethylidene)-1,3-dihydro-2H-indol-2-one
0.029
-
 IC50 for CDK1 is 0.029 mM Homo sapiens (3Z)-5-bromo-3-[2-(4-methylphenyl)-2-oxoethylidene]-1,3-dihydro-2H-indol-2-one
0.029
-
 IC50 for CDK1 is 0.029 mM Homo sapiens (3Z)-5-bromo-3-[2-(4-fluorophenyl)-2-oxoethylidene]-1,3-dihydro-2H-indol-2-one
0.03
-
 IC50 for CDK1 is 0.030 mM Homo sapiens (3Z)-5-bromo-3-(2-oxo-2-phenylethylidene)-1,3-dihydro-2H-indol-2-one