| References: |
PF-03084014 inhibits Notch receptor cleavage in cellular assays using HPB-ALL cells that harbor mutations in both the heterodimerization and PEST domains in Notch1with IC50 of 13.3 nM. PF-03084014 downregulates Notch target genes Hes-1, and cMyc expression in HPB-ALL cells with IC50 of <1 nM and 10 nM, respectively. PF-03084014 inhibits cell growth of a subset of human T-ALL cell lines (HPB-ALL, DND-41, TALL-1,and Sup-T1) through induction of cell cycle arrest and apoptosis with IC50s of 30-100 nM. PF-03084014 reduces proliferation of HUVECs with IC50 of 0.5 μM, and decreases the lumen formation with an IC50 value of 50 nM. PF-03084014 (1 μM) has no antiproliferative effect in MX1 cells; however, it inhibits migration by 95%. PF-03084014 orally administrated in a single dose of 200 mg/kg, causes maximal NICD inhibition for ∼80% in xenograft HPB-ALL tumors. PF-03084014 shows robust antitumor activity in this mode with a maximal tumor growth inhibition of ∼ 92% at dose of 150 mg/kg, accompanied by a significant reduction of NICD/Notch1, tumor mitotic index (Ki67), and apoptosis (activated caspase-3) staining. PF-03084014 (120 mg/kg) induces apoptosis, antiproliferation, reduces tumor cell self-renewal ability, impaires tumor vasculature, and decreases metastasis activity in breast cancer HCC1599 tumor-bearing mice. PF-03084014 treatment displays significant antitumor activity in various types of the breast xenograft models with TGI value of at least 50%. For the detailed information of PF-03084014 (PF-3084014), the solubility of PF-03084014 (PF-3084014) in water, the solubility of PF-03084014 (PF-3084014) in DMSO, the solubility of PF-03084014 (PF-3084014) in PBS buffer, the animal experiment (test) of PF-03084014 (PF-3084014), the cell expriment (test) of PF-03084014 (PF-3084014), the in vivo, in vitro and clinical trial test of PF-03084014 (PF-3084014), the EC50, IC50,and affinity,of PF-03084014 (PF-3084014), For the detailed information of PF-03084014 (PF-3084014), the solubility of PF-03084014 (PF-3084014) in water, the solubility of PF-03084014 (PF-3084014) in DMSO, the solubility of PF-03084014 (PF-3084014) in PBS buffer, the animal experiment (test) of PF-03084014 (PF-3084014), the cell expriment (test) of PF-03084014 (PF-3084014), the in vivo, in vitro and clinical trial test of PF-03084014 (PF-3084014), the EC50, IC50,and affinity,of PF-03084014 (PF-3084014), Please contact DC Chemicals. |
