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Fimepinostat (CUDC-907) is an orally-available small molecule inhibitor that targets both HDAC and PI3K with IC50 values of 19 nM, 54 nM, 311 nM and 39 nM for PI3Kα, PI3Kβ, PI3Kγ and PI3Kδ respectively. Fimepinostat (CUDC-907) potently inhibits class I PI3Ks as well as classes I and II HDAC enzymes. Fimepinostat (CUDC-907) durably inhibits the PI3K-AKT-mTOR pathway and compensatory signaling molecules such as RAF, MEK, MAPK, and STAT-3, as well as upstream receptor tyrosine kinases. Fimepinostat (CUDC-907) shows greater growth inhibition and proapoptotic activity than single-target PI3K or HDAC inhibitors in both cultured and implanted cancer cells.
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Source | Stem Cells Dev (2017). Figure 3. CUDC-907 |
| Method | Western blot | |
| Cell Lines | H3K9ac, H4K8ac, H3K4me2 cell | |
| Concentrations | 500 nM | |
| Incubation Time | 24 h | |
| Results | Interestingly, the combination of both HDAC and PI3K inhibitors failed to induce adipogenesis, suggesting additional possible mechanism by which CUDC-907 promotes adipogenesis |
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Source | Stem Cells Dev (2017). Figure 1. CUDC-907 |
| Method | Adipogenic differentiation | |
| Cell Lines | hMSCs | |
| Concentrations | 500 nM | |
| Incubation Time | 24 h | |
| Results | CUDC-907 treatment of hBMSCs enhanced adipocyte differentiation, as evidenced by the greater Oil Red O staining and quantitative analysis demonstrated that the number of mature adipocytes identified by Nile red staining was higher. |
| Cell Experiment | |
|---|---|
| Cell lines | BT474, N87, H1975, H1993, Calu-6, H460 cells line |
| Preparation method | Cancer cell growth inhibition assay Human cancer cell lines were purchased from American Type Culture Collection (Manassas, VA) and plated at densities of 5,000 to 10,000 per well in 96-well flat-bottomed plates with the recommended culture medium. The cells were then incubated with compounds at various concentrations for 72 hours in culture medium supplemented with 0.5% (v/v) FBS. Growth inhibition was assessed by assay of cellular ATP content using the Perkin-Elmer ATPlite kit. |
| Concentrations | 0~900nM |
| Incubation time | 72 h |
| Animal Experiment | |
|---|---|
| Animal models | Six- to 8-week-old female athymic (nude nu/nu CD-1) or severe combined immunodeficient (SCID) mice Daudi NHL xenograft mouse model |
| Formulation | formulated in 30% Captisol |
| Dosages | 25, 50, and 100 mg/kg |
| Administration | oral gavage |
| Molecular Weight | 508.55 |
| Formula | C23H24N8O4S |
| CAS Number | 1339928-25-4 |
| Solubility (25°C) | DMSO 52 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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| Givinostat hydrochloride monohydrate
ITF2357 (Givinostat, Gavinostat) is a histone deacetylase inhibitor. The IC50 values for maize HDAC preparations HD2, HD-1B and HD-1A are 10, 7.5 and 16 nM respectively. |
| Niltubacin
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| Tubacin
Tubacin (Tubulin Acetylation Inducer) is a highly potent and selective, reversible cell-permeable inhibitor of HDAC6 with IC50 of 0.004µM. |
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