Oral therapy using 6,8-bis-benzylthio-octanoic acid
A benzylthio, octanoic acid technology, applied in the direction of resistance to vector-borne diseases, anhydride/acid/halide active ingredients, medical preparations containing active ingredients, etc.
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example 1
[0108] Example 1 — Oral efficacy of 6,8-bis-benzylthio-octanoic acid in non-small cell lung cancer
[0109] Human H460 NSCLC cells were obtained from the American Type Culture Collection (ATCC) (Cat. No. HTB-177, Manassas, VA). After receiving tumor cells from ATCC, the cells were tested negative for viral contamination using the mouse antibody production (MAP) test performed by the Charles River Labs Molecular Division. Keep tumor cells in T225 tissue culture flasks at 37°C in humidified 5% CO 2 The tissue culture flask contained 50 mL of Roswell Park Memorial Institute (RPMI)-1640 solution with 10% fetal bovine serum (FBS) and 2 mM L-glutamine under atmosphere. Split the cells by trypsinization at a ratio of 1:10 every 2-3 days and resuspend them in fresh medium in a new flask. Cells were harvested for experiments in the same manner at 70-90% confluency.
[0110] CD1-Nu / Nu female mice approximately 4 to 6 weeks old were obtained from Charles River Laboratories. Five mi...
example 2
[0115] Example 2 — Oral efficacy of 6,8-bis-benzylthio-octanoic acid in AML
[0116] C57Bl / 6 mice were injected with 1 million MFL2 cells into the tail vein on day 0 (Pardee, T.S. et al., Experimental Hematology, 2011, 39, 473-485) and started on day 7, Following confirmation of engraftment by bioluminescence imaging, CPI-613 was administered by gavage (daily (except weekends) 300 mg / kg in 50 mg / mL solution in 0.05 N NaOH in 5% dextrose adjusted with 4% glacial acetic acid to pH 7.5-8; 1 animal for the chloroquine experiment), treated intraperitoneally (IP) with chloroquine (daily (except weekends) 200 μL (approximately 100 mg / kg) of 10 mg / mL solution in PBS; Chlr; three animals ), treated with metformin orally (1 mg / mL in ad libitum drinking water), or with CPI-613 (as above, 300 mg / kg, gavage daily) and chloroquine (as above, 200 μL daily IP; 4 animals) or metformin (as described above, 1 mg / mL in drinking water ad libitum) and then survived. Control animals (1 animal in...
example 3
[0118] Example 3 — Oral efficacy of 6,8-bis-benzylthio-octanoic acid in ALL
[0119] Balb / c mice were injected with 1 million Baf3-p210 cells into the tail vein on day 0, and starting on day 3, after engraftment was confirmed by bioluminescence imaging, they were treated with saline (control), doxorubicin (3 mg / kg IP in 200 μL PBS) or doxorubicin (3 mg / kg IP in 200 μL PBS) plus CPI-613 (250 mg / kg gavage, CPI-613 in 0.05N NaOH in 5% dextrose 25 mg / mL solution, adjusted to pH 7.5-8 with 4% glacial acetic acid) and survived. Doxorubicin was administered once daily for three consecutive days, and CPI-613 was administered once daily until death. P-values were determined by log-rank test.
[0120] The results are shown in Figure 4 middle. This example demonstrates that oral administration of 6,8-bis-benzylthio-octanoic acid in combination with doxorubicin significantly prolongs the survival of Philadelphia chromosome positive B-cell ALL tumor-bearing mice compared to doxor...
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