Cells. Add pacritinib before pracinostat was tested antagonistic in all cell lines on ED90. Pracinostat is effective in various animal models of human AML Pracinostat as a single therapy has been tested in various mouse models of human AML. Treatment of mice M, The induced pracinostat with MV4 xenografts 11, a significant inhibition of tumor growth, 59 and 116% respectively. Complete Requests JNJ 26854165 p53 inhibitor reference requests getting tumor regression was observed in 6 of 10 animals at the end of treatment after a dose of 50 mg. To the anti-tumor efficacy in a model that is less sensitive to pracinostat, prime to M1 M2 M3 M4 M5 Unknown 0.0 0.5 1.0 1.5 2.0 2.5 AML Shore precursor cells re-based Is to determine , IC50 of proliferation 0.0 0.2 0.4 0.6 0.8 M2 MOLM HL 60 13 11 MV4 M5a M5 M5 M6 M7 THP 1 HEL 92.
1.7 JAK2V617F JAK2V617F MOLM SET 2 16 SH 2 M0 M2 M4 1 ME cell F36 P ID FAB M6 M6 1 KG AML cell lines IC50 comments on the proliferation of GM-CSF dep. NLL FUS AF9. FLT3 ITD, FLT3-ITD CBFB FUS MYH11. Figure 2 Pracinostat a potent inhibitor of cell proliferation in cell lines and primary Re LAB LAB cells. IC50 SGX-523 c-Met inhibitor cell lines tested in studies of 48 h of cell proliferation, FAB classification of AML British American Fran-cells. The results show means.d. at least three rounds of experiments, each performed in triplicate. Prim Re AML of 16 patients were expanded and then treated in d12 d13 with dimethyl sulfoxide or pracinostat serially in nine steps of 10 mM diluted to 1.5 nM for 48 h. The results show that more than two rounds of the explosion expansion / proliferation assays.
Ic gray Ties shaded Fl Chen blasts are carrying the FLT3-ITD. Table 1 When combined in vitro and pracinostat pacritinib Sequence Lineage CI ED50s.d. CI ED90s.d. n the meantime 0.890.1 0.770.1 1.490.3 first MOLM 13 SB939 SB1518 2 1.480.4 1.500.1 1.320.0 0.550.1 0.410.2 0.720.1 0.550.3 first MV4 same SB939 first 11 1.690.5 At the same time 60 2.171.1 first SB1518 2 2.491.3 1.40.2 1.350.2 1.350.5 1.570.3 1.670.2 first SB939 SB1518 1.60.2 1.70.1 first four HL 1.30.5 1.00.2 KG1 same first two SB939 SB1518 1.80 first. At the same time, a 0.91 1.27 1.13 0.95 1 2.70.6 SET 2 SB939 SB1518 first 0.98 1.41 2.070.9 2.401.4 0.990.0 0.810.1 SB1518 SB939 first same HEL92.1.7 first first 2.121.0 2300 2 .2 .7 .60 At the same SB939 first 0.740.2 0.80.3 0.980.3 1.810.8 1.91.
0 F36P first three SB1518 Abbreviations: CI, Combinatorial Index, GM-CSF, granulocyte-macrophage colony-stimulating factor mt-mutant, by weight, wild type. SB939 and SB1518 in AML V Diermayr Novotny et al 4 blood cancer and 2012 Journal of Macmillan Publishers Limited cell proliferation in vitro, Mice with xenografts with HEL92.1.7 pracinostat to 75 or 125 mg / kg every treated for two days for a total of 17 days. Dose-dependent Independent TGI was observed, which was statistically significant at the h Higher dose. Pracinostat was very well tolerated in both studies. See Erg get Complementary to Table 1 for a report U efficacy in various models. The effectiveness of the pracinostat in a physiologically relevant model to determine HL-60 cells were transplanted orthotopically.
Treatment with 125 mg / kg in a schedule pracinostat three times a week starting as soon as the disease was based on d30, but before the start of the first symptoms, including normal L Hmung the hind legs. Pracinostat treatment led to a delay Gerung of 17 days after illness onset and a 50% reduction in Todesf Lle by progressive AML study on D24. Wei E Blutk Rperchen on d15 of the study were six times h Ago and the number of lymphocytes, mice three times higher than in animals treated with vehicle compared with disease-free SCID-M. The treatment Pracinostat