Indirubin derivatives R1 R2 R3 R4 R5 R6 Main effects/properties Reference
Core structure of indirubins Indirubin -H -H -H -H =O -H Antitumor effect
[4 –10 ] N-Ethyl-indirubin -CH2 CH3 -H -H -H =O -H
Higher antitumor potencies compared to indirubin
[15 –17 ] -H -X -H -H =O -H Indirubin-3′-monoxime -H -H -H -H =NOH -H Inhibition of CDKs with high potency [9 , 18 ] 5-Iodoindirubin-3′-monoxime -H -I -H -H =NOH -H Inhibition of GSK-3β
[19 ] Indirubin-5-sulfonic acid -H -SO3 H -H -H =O -H Indirubin-5-sulfonamide -H -SO2 NH2 -H -H =O -H 5-Halogenoindirubins -H -X -H -H =O -H C6 and C5, C6 halogen substit. of indirubin -H -H or -X -X -H =O -H More potent CDK and GSK-3β inhibitors [20 ] 3′-Substituted -H or -CH3 -H -H -X =NOH, =NOCH3 , =NOCOCH3 and others -H Lacking the inhibitory effects towards CDKs and GSK-3β but still inducing cell death [21 ] E564 -H -H -H -H =NOCH2 CH2 OCH2 CH2 OH -H Inhibitory effect towards STAT3 signaling, contributing to apoptosis in human cancer cells
[22 ] E728 -H -OCH3 -H -H =NOH -H E804 -H -H -H -H =NOCH2 CH2 CH(OH)CH2 OH -H 5-Fluoro-indirubinoxime -H -F -H -H =NOH -H
Antitumor activity in vitro and in several animal models
[23 –27 ] 5-Trimethylacetamino-indirubinoxime -H -NH -H -H =NOH -H 5-Nitro-indirubinoxime -H -NO2 -H -H =NOH -H Additional anti-inflammatory properties in HUVECs [28 ]
7-Azaindirubin-3′-oxime
Potent antiproliferative properties in cancer cell lines and inhibition of a series of kinases
[29 ] 7-Bromo-5′-carboxyindirubin-3′-oxime -H -H -H -Br =NOH -COOH Novel inverse binding mode, with improved selectivity for DYRK kinases [30 ] 5-Diphenylacetamido-indirubin-3′-oxime -H -NHCOC6 H5 )2 -H -H =NOH -H Novel mitochondria-targeting agent with antileukemic activity [31 ] 5′-OH-5-nitro-indirubin oxime (AGM130) -H -NO2 -H -H =NOH -OH Improved solubility compared to indirubin and effective induction of apoptosis of imatinib-resistant CML cells [32 ]
