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TA-01 inhibitors inhibit cardiac development when applied at 5 μM. TA-01 shows an almost complete inhibition of cardiogenesis when applied at 5 μM. TA-01 shows reduced expression of all tested mesoderm markers and the pre-cardiac marker Isl-1.
| Cell Experiment | |
|---|---|
| Cell lines | Human pluripotent stemcell lines HES-3 and H7 |
| Preparation method | Human pluripotent stemcell lines HES-3 and H7 were seeded at 2.5 × 106 cells/12-ULA well in BSFS medium with cell line optimized concentrations of CHIR99021 for 24 h (Supplemental Fig. S7). Thereafter the 2,4,5-trisubstituted azoles or IWP-2 or IWR-1 were added at a concentration of 5 μM (2.5 μM for IWR-1) either from 1-8 days or from 4-8 days. Dissociated EBs showed an average of 50–60% NKX2-5+ cells on day 11 when either 2,4,5-trisubstituted azoles, IWP-2 and IWR-1 were applied from 4-8 days i.e. at the post mesoderm stage. In comparison to premesoderm treatment only HES-3 showed high cardiomyocyte expansion fold with SB203580 (days 1-8) (Fig. 3A). To confirm that 2,4,5-trisubstituted azoles had no negative impact on cell viability, we analyzed the cell growth kinetics. EBs treated with IWP-2 and IWR-1 generated significantly fewer cells compared to 2,4,5-trisubstituted azoles in both cell lines (Fig. 3A). Metabolismrates of EBs measured with MTT showed an increase with TA-01 but not with IWR-1 and IWP-2 during the compound induction period. |
| Concentrations | 5 μM |
| Incubation time | - |
| Animal Experiment | |
|---|---|
| Animal models | |
| Formulation | |
| Dosages | |
| Administration | |
| Molecular Weight | 351.32 |
| Formula | C20H12F3N3 |
| CAS Number | 1784751-18-3 |
| Solubility (25°C) | DMSO ≥ 30 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
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