Table 2.
Cytotoxicity (LC50) of PTL and selected PTL analogs against patient-derived primary Acute Myeloid Leukemia samples (AML01) and human umbilical cord blood cells (hUBC) as determined based on cell viability assays. IC50 values refer to the compound inhibitory activity on hUBC as measured via a plate-based colony formation assay. LC50 and IC50 values are mean ± SD (n = 3). n.d. = not determined.
| Compound | Name | AML01 LC50 (μM) |
hUBC LC50 (μM) |
hUBC IC50 (μM) |
|---|---|---|---|---|
| PTL | parthenolide | 6.1 ± 0.3 | >20 (42)a | 12.5 ± 0.6 |
| 13 | PTL-14-20 | 2.2 ± 0.1 | n.d. | n.d. |
| 23a | PTL-14-26-epi1 | 2.5 ± 0.1 | 5.4 ± 0.5 | 7.5 ± 0.7 |
| 23b | PTL-14-26-epi2 | 3.1 ± 0.3 | >5 (8.8)a | 4.6 ± 0.5 |
| 26a | PTL-14-27-epi1 | 3.2 ± 0.1 | 3.7 ± 0.4 | 6.2 ± 0.6 |
| 26b | PTL-14-27-epi2 | 5.1 ± 0.5 | 5.5 ± 0.6 | 5.4 ± 0.5 |
| 28 | PTL-14-28 | 22.4 ± 5.6 | n.d. | n.d. |
| 29 | PTL-14-29 | 23.6 ± 9.3 | n.d. | n.d. |
| 24 | PTL-14-30 | 8.5 ± 1.0 | n.d. | n.d. |
| 18a | PTL-9-24-epi1 | 2.6 ± 0.2 | n.d. | n.d. |
| 18b | PTL-9-24-epi2 | 10.0 ± 2.1 | n.d. | n.d. |
| 22a | PTL-9-26-epi1 | 3.4 ± 0.3 | >5 (7.3)a | 13.2 ± 1.0 |
| 22b | PTL-9-26-epi2 | 2.6 ± 0.2 | 2.7 ± 0.3 | 2.4 ± 0.2 |
| 25a | PTL-9-27-epi1 | 5.1 ± 1.0 | >5 (12.2)a | 31.6 ± 5 |
| 25b | PTL-9-27-epi2 | 3.1 ± 0.1 | >5 (10.9)a | 5.0 ± 0.4 |
| 27 | PTL-9-28 | 40 ± 20 | n.d. | n.d. |
a
Extrapolated values beyond concentration range tested.