US9187470, 104 (SB203580) BDBM192501 US10865384, Compound SB203580
CHEMBL518935 resveratrol (E)-dehydrodimer BDBM50259651 resveratrol trans-dehydrodimer
Azo-Resveratrol CHEMBL2208146 BDBM50486146
CHEMBL1173450 BDBM50322614 Resveratrol Potassium4,-Sulfate
Resveratrol Potassium3-Sulfate BDBM50322615 CHEMBL1173685 CHEMBL1823816
BDBM23926 (E)-resveratrol cid_445154 US20240398793, Compound 1 Resveratol 5-[(E)-2-(4-hydroxyphenyl)ethenyl]benzene-1,3-diol trans-resveratrol resveratrol US11866416, Example 7 CHEMBL165 Stilbene, 2f
3-(gamma,gamma-dimethylallyl)resveratrol BDBM50269596 CHEMBL457145
BDBM50269597 CHEMBL446319 3-(2,3-dihydroxy-3-methylbutyl)resveratrol
CHEMBL503412 resveratrol (E)-dehydrodimer 11-O-beta-D-glucopyranoside BDBM50269812
5-[(1Z)-2-(4-hydroxyphenyl)ethenyl]benzene-1,3-diol 5-[(Z)-2-(4-hydroxyphenyl)vinyl]benzene-1,3-diol BDBM50131698 CHEMBL87333 US20240398793, Compound 2 cis-resveratrol (Z)-resveratrol
Resveratrol hexanoic acid CHEMBL504510 BDBM50271238 6-{4-[(1E)-2-(3,5-dihydroxyphenyl)ethenyl]phenoxy}hexanoic acid
4-{4-(4-fluorophenyl)-2-[4-(methylsulfinyl)phenyl]-1H-imidazol-5-yl}pyridine SB-203580 4-[4-(4-fluorophenyl)-2-(4-methanesulfinylphenyl)-1H-imidazol-5-yl]pyridine BDBM13336 cid_176155 4-[4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-1H-imidazol-5-yl]pyridine CHEMBL10 SB203580
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- LanthaScreen Eu Kinase Binding Assay Table 3: Small molecules were tested for their inhibitory activities towards casein kinase 1 delta (CK1δ) and 1 epsilon (CK1ϵ). The in vitro LanthaScreen Eu kinase binding assay was used to determine the IC50 values for 15 of the synthesized compounds and 5 commercial inhibitors including SB203580 (Table 3). Tested compounds displayed a wide range of affinity between 6.8 nM (high affinity=strong inhibition) to values over 1000 nM (low affinity=very weak inhibition).
- Inhibition Assay The actual target(s) whereby the most active substituted trans-stilbenes inhibit the TNFα-induced activation of NF-κB remains to be identified. Resveratrol has been shown to suppress the TNF-induced phosphorylation and nuclear translocation of the p65 subunit of NF-κB.38 Both IKKα and IKKβ are able to catalyze the phosphorylation of p65, although through different signaling pathways,39 and are potential targets. Likewise, one or more of the kinases that activate IKK by phosphorylation, in response to TNFα or to the numerous other activators of NF-κB,35 may be the targets.
- Kinase Assay Table 2: The p38 MAPK IC50 values of selected compounds except IM-32 to IM-44 were determined using the HitHunter p38 MAP kinase binding assay from DiscoveRx Corporation (Fremont, Calif., USA). The p38 MAPK IC50 values of IM-32 to IM-44 and the CK1 IC50 values of selected compounds were determined using LanthaScreen Eu kinase binding assay from Invitrogen (Life Technologies, Carlsbad, Calif., USA). The assays were performed following the manufacturers' protocols in white 384-well plates (Cat. No. 3572; Corning Incorporated, Corning, N.Y., USA). SB203580 was used as the control in all assays. For the HitHunter p38 MAP kinase binding assay the compounds were dissolved in DMSO (5 mM stocks) and diluted to a final concentration of 2% (vol/vol) DMSO for all assays. Recombinant GST-tagged active p38α MAP kinase enzyme (Millipore, Billerica, Mass., USA) was used for the HitHunter p38 MAP kinase binding assay. For the LanthaScreen Eu kinase binding assay the compounds were dissolved in DMSO (5 mM stocks) and diluted to a final concentration of 1% (vol/vol) DMSO for all assays. Each data point was done in triplicate. The assay was run using JANUS Automated Workstation according to the protocol developed using WinPREP software (Perkin Elmer Inc., Waltham, Mass., USA). Tecan Infinite M1000 microplate reader (Tecan Group Ltd., Minnedorf, Switzerland) was used for luminescence measurements (HitHunter p38 MAP kinase binding assay) and fluorescence measurements (LanthaScreen Eu kinase binding assay; ex=340 nm, em=665, 615 nm). All data analysis was performed using GraphPad Prism 5 software (GraphPad Software Inc.). Inhibition curves and IC50 values were generated by nonlinear regression analysis and data represent mean±SEM.