Table 1.
ITDRFCETSA to Rank Intracellular B-Raf Target Engagement.
| Compound | Molecular Target | B-Raf ITDRFCETSA pEC50 |
|---|---|---|
| Dabrafenib | Pan Raf | 7.8 ± 0.1 |
| LY3009120 | Pan Raf | 7.6 ± 0.2 |
| AZ628 | Pan Raf | 6.4 ± 0.1 |
| Vemurafenib analog | B-Raf V600E | 6.2 ± 0.1 |
| PLX4720 | B-Raf V600E | 5.8 ± 0.1 |
| Vemurafenib | B-Raf V600E | 5.8 ± 0.5 |
| AZ12823138 | Pan Raf | 5.6 ± 0.1 |
| Compound 4 | Pan Raf | 4.6 ± 0.0 |
| PLX5568 | C-Raf | <4.5 |
| Compound 10d | C-Raf | <4.5 |
| CH-5126766 | Raf/MEK | 5.0 ± 0.4 |
| Selumetinib | MEK | <4.5 |
| PD325901 | MEK | <4.5 |
| GDC-0623 | MEK | <4.5 |
| SCH772984 | ERK | <4.5 |
| Compound 35 | ERK | <4.5 |
| Imatinib | Abl, c-kit, PDGFR | <4.5 |
| Crizotinib | ALK, MET | <4.5 |
pEC50 was determined following 2 h incubation with live A375 cells for a range of Pan Raf and B-Raf inhibitors as well as inhibitors of alternative targets in the RAS-RAF-MEK-ERK signaling pathway and unrelated kinase targets. Data are the mean ± standard deviation of ⩾3 technical repeats. Example raw data are reported in Supplemental Figure S4.