体外研究
(In Vitro) | PF15 (0-1000 nM; 72 h) shows good anti-proliferation activity in MV4-11, Molm-13 and BaF3 cells (transformed ITD, ITD-D835V, and ITD-F691L mutations)[1].
PF15 (1, 3, 10, 30, 100, 300, 1000 nM; 6 h) obviously induces FLT3 degradation in a dose-dependent manner and (10, 30, 100, 300, 1000 nM; 6 h) dramatically inhibits the phosphorylation of FLT3 and STAT5 in BaF3-FLT3-ITD cells[1].
PF15 (10, 30, 100, 300, 1000 nM; 6 h) sharply downregulates the phosphorylation of FLT3 and STAT5 at 100 nM in both BaF3-FLT3-ITD-D835V and BaF3-FLT3-ITD-F691L cells[1].
PF15 (100 nM; 1, 3, 6, 12, 24 h) induces FLT3 degradation in a time-dependent manner from 1 h to 24 h[1].
PF15 (15.6, 31.2, 62.5, 125, 250, 500, 1000, 2000 nM; 24 h) induces FLT3 degradation with a DC50of 76.7 nM[1].
Cell Proliferation Assay[1] | Cell Line: | MV4-11, Molm-13, BaF3 cells (transformed ITD, ITD-D835V, and ITD-F691L mutations) | | Concentration: | 0-1000 nM | | Incubation Time: | 72 h | | Result: | Exhibited anti-proliferation activity with IC50s of 4.83 nM (MV4-11), 4.01 nM (Molm-13) and 7.85, 120.1, 116.6 nM (for transformed BaF3 cells harboring ITD, ITD-D835V, and ITD-F691L mutations respectively). |
Western Blot Analysis[1] | Cell Line: | BaF3-FLT3-ITD, BaF3-FLT3-ITD-D835V, BaF3-FLT3-ITD-F691L cells | | Concentration: | 1, 3, 10, 30, 100, 300, 1000 nM | | Incubation Time: | 6 h | | Result: | Induced FLT3 degradation when at 3 nM and in a dose-dependent manner in BaF3-FLT3-ITD cells.
Dramatically inhibited the phosphorylation of FLT3 and STAT5 when concentration up to 30 nM in BaF3-FLT3-ITD cells, and at 100 nM in both BaF3-FLT3-ITD-D835V and BaF3-FLT3-ITD-F691L cells. |
Western Blot Analysis[1] | Cell Line: | BaF3-FLT3-ITD cells | | Concentration: | 100 nM | | Incubation Time: | 1, 3, 6, 12, 24 h | | Result: | Significantly induced FLT3 degradation in a time-dependent manner, and FLT3 completely degraded when at 24 h. |
Western Blot Analysis[1] | Cell Line: | BaF3-FLT3-ITD cell | | Concentration: | 15.6, 31.2, 62.5, 125, 250, 500, 1000, 2000 nM | | Incubation Time: | 24 h | | Result: | Notably induced FLT3 degradation when at 125 nM, and DC50was 76.7 nM. |
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体内研究
(In Vivo) | PF15 (10 or 20 mg/kg; i.p.; once daily for 10 days) shows good tumor growth inhibition with an inhibitory rate of 58.4% at dosage of 10 mg/kg, and when up to 20 mg/kg displays higher inhibitory rate[1].
PF15 (twice daily (20 mg/kg), once daily (40 mg/kg); 12 days; i.p.) prolongs the median survival up to 15 days (negative control group is 11 days) in BaF3-FLT3-ITD in situ model[1].
| Animal Model: | Female NOD/SCID mice (BaF3-FLT3-ITD xenograft model)[1]. | | Dosage: | 10 or 20 mg/kg | | Administration: | Intraperitoneal injection; once daily for 10 days. | | Result: | Achieved good tumor growth inhibition with an inhibitory rate of 58.4% (10 mg/kg), meanwhile, when at 20 mg/kg displayed higher inhibitory rate.
Hardly caused side effects on heart, liver, and kidney (both of the treatment groups). |
| Animal Model: | Female BALB/c nude mice (BaF3-FLT3-ITD in situ model)[1]. | | Dosage: | 20, 40 mg/kg | | Administration: | Intraperitoneal injection; twice daily (20 mg/kg), once daily (40 mg/kg); 12 days. | | Result: | Prolonged the median survival from 11days to 15 days (both of the treatment groups). |
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