Background
Materials and methods
Peptides
Cell lines
Therapeutics
Fluorophore
Cell viability assay
Live imaging
Imaging
Western blots and lysates
Mouse model; inflammatory breast cancer
Toxicity study
Patient-derived xenografts; breast and lung
Patient-derived xenografts; glioblastoma
Glioblastoma cell viability assay
Results
Hydrocarbon stapling of EJ1 increases intracellular activity
SAH5-EJ1 is effectively delivered intracellularly and throughout the body
Treatment | N | SAH-EJ1 concentration (µg/mL) | |||||
---|---|---|---|---|---|---|---|
0.5 h | 1 h | 2 h | 4 h | 8 h | 24 h | ||
Male | |||||||
Control | 3 | × | BQL | × | × | × | × |
5 mg/kg | 6 | 1.04 | 0.548 | BQL | BQL | BQL | BQL |
6 | 1.36 | 0.603 | BQL | BQL | BQL | BQL | |
6 | 0.658 | BQL | BQL | BQL | BQL | BQL | |
Average |
1.02 ± 0.35
|
0.576 ± 0.039
| – | – | – | – | |
10 mg/kg | 6 | 0.684 | 0.568 | BQL | BQL | BQL | BQL |
6 | 0.514 | 0.589 | BQL | BQL | BQL | BQL | |
6 | 0.716 | 0.839 | BQL | BQL | BQL | BQL | |
Average |
0.638 ± 0.11
|
0.665 ± 0.150
| – | – | – | – | |
15 mg/kg | 6 | 0.75 | BQL | BQL | BQL | BQL | BQL |
6 | 1.07 | 0.63 | 0.551 | BQL | BQL | BQL | |
6 | 0.884 | 0.683 | BQL | BQL | BQL | BQL | |
Average |
0.901 ± 0.16
|
0.657 ± 0.037
|
0.551
| – | – | – | |
Female | |||||||
Control | 3 | × | BQL | × | × | × | × |
5 mg/kg | 6 | 0.561 | BQL | BQL | BQL | BQL | BQL |
6 | 0.555 | 0.508 | BQL | BQL | BQL | BQL | |
6 | 0.59 | 0.55 | BQL | BQL | BQL | BQL | |
Average |
0.569 ± 0.019
|
0.529 ± 0.030
| – | – | – | – | |
10 mg/kg | 6 | 0.53 | 0.565 | BQL | BQL | BQL | BQL |
6 | 0.616 | BQL | BQL | BQL | BQL | BQL | |
6 | 0.539 | 0.518 | BQL | BQL | BQL | BQL | |
Average |
0.562 ± 0.047
|
0.542 ± 0.033
| – | – | – | – | |
15 mg/kg | 6 | 0.508 | 0.588 | BQL | BQL | BQL | BQL |
6 | 0.599 | BQL | BQL | BQL | BQL | BQL | |
6 | BQL | 0.55 | BQL | BQL | BQL | BQL | |
Average |
0.554 ± 0.064
|
0.569 ± 0.027
| – | – | – | – |
SAH5-EJ1 promotes cell death in EGFRvIII glioblastoma-derived cell lines and increases survival in mouse models
SAH5-EJ1 is effective in vitro and prolongs survival in PDX models of lung cancer within a therapeutic window
SAH5-EJ1 inhibits basal models of breast cancer
SAH5-EJ1 effectively targets triple negative inflammatory breast cancer
Male | Female | |||||||
---|---|---|---|---|---|---|---|---|
Control | 5 mg/kg | 10 mg/kg | 15 mg/kg | Control | 5 mg/kg | 10 mg/kg | 15 mg/kg | |
BUN (mg/dL) | 30 ± 9.7 | 26 ± 2.2 | 31 ± 7.3 | 23 ± 2.9 | 22 ± 5.2 | 19 ± 2.2 | 19 ± 3.0 | 22 ± 2.5 |
ALP (IU/L) | 54 ± 12.9 | 68 ± 13.8 | 73 ± 19.7 | 58 ± 10.5 | 95 ± 38.8 | 88 ± 33.2 | 70 ± 48.4 | 62 ± 18.4 |
ALT (IU/L) | 107 ± 29.7 | 124 ± 71.5 | 96 ± 28.3 | 67 ± 32.3 | 88 ± 22.8 | 79 ± 35.0 | 61 ± 18.5 | 90 ± 27.2 |
AST (IU/L) | 87 ± 28.5 | 92 ± 28.6 | 83 ± 23.6 | 63 ± 13.5 | 107 ± 16.2 | 80 ± 8.3a | 83 ± 19.0 | 93 ± 12.5 |
TBIL (mg/dL) | 0.1 ± 0.04 | 0.2 ± 0.05 | 0.2 ± 0.04 | 0.2 ± 0.05 | 0.2 ± 0 | 0.2 ± 0.05 | 0.1 ± 0.05 | 0.1 ± 0b |
N | 5 | 4 | 5 | 4 | 5 | 5 | 5 | 4 |