SOTICLESTAT TAK-935 TAK935 OV-935 OV935 BDBM50583519
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- ChEMBL_2261253 (CHEMBL5216264) Inhibition of IDO1 in human SK-OV-3 cells
- ChEMBL_2339809 Inhibition of PI3Kalpha (unknown origin) in human SK-OV-3 cells
- ChEMBL_2057394 (CHEMBL4712395) Inhibition of acid ceramidase in human SK-OV-3 cell lysates
- ChEMBL_2522715 Inhibition of PRMT5 in human Z138 cells assessed as effect on PHLDA3 expression incubated for 2 to 4 days by Western blot analysis
- ChEMBL_2336714 Inhibition of PKB phosphorylation in human SK-OV-3 cells incubated for 1 hrs by ELISA
- ChEMBL_2337681 Inhibition of pax2 (unknown origin) in human SK-OV-3 cells measured after 24 hrs by immunoblotting analysis
- ChEMBL_2501556 Inhibition of PI3K alpha in human SK-OV-3 cells incubated for 2 hrs by Western blot analysis
- ChEMBL_2199068 (CHEMBL5111584) Inhibition of GCN2 in human SK-OV-3 cells assessed as reduction in phosphorylation of eIF2alpha by cellular assay
- ChEMBL_2193357 (CHEMBL5105717) Inhibition of alphavbeta3 integrin receptor-mediated cell adhesion to fibrinogen in human SK-OV-3 cells expressing alphavbeta5 integrin receptor
- ChEMBL_2265667 Inhibition of PI3Kalpha H1047R mutant in human SK-OV-3 cells assessed as protein phosphorylation incubated for 2 hrs by fluorescence assay
- ChEMBL_2237616 (CHEMBL5151512) Inhibition of PI3Kalpha in human SK-OV-3 cells assessed as reduction in AKT phosphorylation at S473 residue incubated for 30 mins
- ChEMBL_2199091 (CHEMBL5111607) Inhibition of GCN2 in human SK-OV-3 cells assessed as reduction in phosphorylation of eIF2alpha in presence of human serum by cellular assay
- ChEMBL_2482679 Inhibition of PI3Kalpha in human SK-OV-3 cells assessed as reduction in AKT phosphorylation at S473 residue incubated for 2 hrs by Western blot analysis
- ChEMBL_2094584 (CHEMBL4775847) Inhibition of CD73 in human SK-OV-3 cells incubated for 60 mins before addition of AMP and further incubated for 60 mins by colorimetric assay
- ChEMBL_2576989 Inhibition of GLUT1 in human SK-OV-3 cells assessed as decrease in conversion of D-[5-3H(N)]-glucose to 3H2O incubated for 24 hrs by liquid scintillation counting
- ChEMBL_2078882 (CHEMBL4734673) Inhibition of IDO1 in human SK-OV-3 cells assessed as effect on KYN level using L-tryptophan as substrate incubated for 18 hrs by 4-(dimethylamino)benzaldehyde based absorbance method
- ChEMBL_2228094 (CHEMBL5141607) Inhibition of N-terminal recombinant PKMYT1 (76 to 362 residues) in CCNE1 amplified human FU-OV-1 cells assessed as phosphorylation of CDK1 at Thr14 incubated for 2 hrs by AlphaLisa assay
- Titre Blue Assay The cell titre blue viability (Promega, USA) assay provides a homogenous, fluorometric method for estimating the number of viable cells. It uses the dark blue indicator dye resazurin to measure the metabolic capacity of cells which is an indicator of cell viability. Viable cells are able to reduce resazurin into resorufin (pink) which is highly fluorescent. Briefly, U2OS or SK-OV-3 (6×103 cells/mL) were seeded into 384-well plates and were incubated for 24 h. Compounds (at a range of concentrations) were added using the ECHO 550 liquid handler (Labcyte, USA) and then left at 37° C. for 96 h. Titre blue reagent was added to each well and left at 37° C. for 3-4 h. Fluorescence was measured using the Envision machine (Perkin Elmer, UK).In general, activity possessed by compounds of the formula I, may be demonstrated in the Arrayscan and Cellisa assays by an IC50 value of less than 15 μM. Suitably compounds have an IC50 value of less than 10 μM in these assays, more suitably less than 5 μM, even more suitably less than 2 μM and most suitably less than 1 μM. Preferred compounds of the invention have an IC50 value of less than 500 nM in the Arrayscan and Cellulisa assays.
- Cell-Based ELISA (Cellisa) Assay U2OS cells (5-8×104 cells/mL) or SK-OV-3 cells (5-8×104 cells/mL) were seeded into 96-well plates and incubated at 37° C. for 48 h. Compounds were then added at a range of concentrations and incubated for 1 h before addition of 17-AAG (250 nM). Cells were then incubated for 18 h. The medium was removed washed 2× with PBS and cells were then fixed with fixing solution (4% paraformaldehyde, 0.3% TritonX-100 in PBS) for 30 min at 4° C. The plates were then washed 2× with PBS before blocking with 5% milk for 30 min at 37° C. After washing the plates 4× with 0.1% Tween-20/deionised water, HSP72 antibody (SPA-810, Enzo Life) was added for 1.5 h at 37° C. Following 4× washes, the plates were incubated with europium-labelled anti-mouse antibody (0.6 ug/ml) in Delfia assay buffer (Perkin Elmer) for 1 h at 37° C. After washing the plates, Delfia enhancement solution was added, shaken for 10 min before reading in the Envision plate reader (Perkin-Elmer) with excitation at 340 nm and emission at 615 nm. The plates were washed again before protein determination using the bicinchoninic acid assay (BCA assay, Pierce Biotechnology). The europium counts were normalised for the amount of protein in each well. The 50% inhibitory concentration value of the compound was then calculated.