TAE226 inhibited cancer-cell growth with model-dependent potency. After 48 hours, GI50 values were 0.26 ± 0.062 μM in MIA PaCa-2 and 3.6 ± 0.93 μM in PANC-1 (means ± SEM; n = 4 and 3, respectively). [2]
Target responses depend on conditions. In six NSCLC lines, FAK and IGF-IR phosphorylation was not significantly inhibited through 5 μM in serum-containing cultures, while mutant-EGFR signaling was suppressed. Under serum-starved, IGF-I-stimulated conditions, IGF-IR phosphorylation was inhibited in four tested lines. [3]
FAK–TAE226 binding structure
Biochemical assay · Avian FAK kinase domain (residues 411–686) [1]
TAE226 occupies the ATP pocket and stabilizes a helical DFG conformation.
Literature-Reported Treatment Conditions
- Method
- X-ray co-crystallography with molecular replacement and refinement.
- Co-treatment
- None; single-agent TAE226 conditions selected.
- Reported limits
- Salt/solvate and tested-batch analytical characterization not specified.
Methods and source locations
Compound reported in the paper: NVP-TAE226; Compound label in the paper: TAE226
Evidence concerns the named research compound; no equivalence of a tested batch to an Adooq lot is established.
Results; Figures 1, 3a and Table 1; structure determination methods
TAE226-bound FAK structure: One crystal dataset; Table 1. — Table 1, TAE226 column
Binding mode: Figure 3a viewed with Results text. — Results; Figure 3a
Purified FAK inhibition
Biochemical assay · Purified avian FAK411–686 with FAK31–405 substrate [1]
TAE226 inhibited FAK under the reported ATP/substrate conditions.
Literature-Reported Treatment Conditions
- Treatment concentration
- 0.05–100 nM (inhibitor titration)
- Exposure duration
- 30 min
- Method
- Anti-phosphotyrosine ELISA; 10 nM kinase, 1 mM ATP, 1 µM substrate; Hill-slope fit.
- Co-treatment
- None; single-agent TAE226 conditions selected.
- Reported limits
- Meaning of Table 2 ± term and independent experiment count not defined; six activity determinations per concentration are reported. Final solvent concentration and explicit zero-inhibitor control details not specified in assay description.
Methods and source locations
Compound reported in the paper: NVP-TAE226; Compound label in the paper: TAE226
Evidence concerns the named research compound; no equivalence of a tested batch to an Adooq lot is established.
Table 2 and footnote; Inhibition curves and IC50 value
Purified FAK kinase inhibition: Six activity determinations per concentration; ± semantics not defined in Table 2. — Table 2; Inhibition curves and IC50 value
Cancer-cell growth profiling
Cell-based study · Panel of 37 cancer cell lines [2]
TAE226 growth-inhibition potency varied across the panel.
Literature-Reported Treatment Conditions
- Exposure duration
- 48 h
- Method
- Sulforhodamine B for adherent lines; AlamarBlue for suspension lines; growth controls and time-zero controls for net growth.
- Vehicle
- DMSO stock; final vehicle percentage not specified.
- Co-treatment
- None; single-agent TAE226 conditions selected.
- Reported limits
- Absolute final titration range not stated. Suspension assay uses gross rather than net growth; panel summary combines assay types.
Methods and source locations
Compound reported in the paper: NVP-TAE226; Compound label in the paper: TAE226
Evidence concerns the named research compound; no equivalence of a tested batch to an Adooq lot is established.
Cellular proliferation assays; Table 1 and footnote
Panel growth inhibition: Author-reported panel summary; not recomputed. — Results and discussion, opening paragraph
MIA PaCa-2 net growth inhibition: Sulforhodamine B at 48 h. — Table 1 and footnote
PANC-1 net growth inhibition: Sulforhodamine B at 48 h. — Table 1 and footnote
Condition-dependent NSCLC signaling response
Cell-based study · PC-9, HCC827, NCI-H1975, RPC-9, NCI-H1299 and NCI-H1819; S1 subset PC-9, RPC-9, NCI-H1299, NCI-H1819 [3]
In serum-containing cultures, phospho-FAK and phospho-IGF-IR persisted through 5 μM, whereas mutant-EGFR signaling was inhibited. Serum-starved/IGF-I-stimulated conditions showed IGF-IR inhibition.
Literature-Reported Treatment Conditions
- Treatment concentration
- Figure 1: 0, 0.02, 0.2, 2, 5 μmol/L. S1: 0, 0.02, 0.2, 2 μmol/L.
- Exposure duration
- Figure 1 exposure duration not specified in retrieved caption/method. S1: 3 h serum starvation, 2 h treatment, then 15 min IGF-I stimulation.
- Method
- Western blot; total proteins and actin controls; S1 includes unstimulated and stimulated zero-drug controls.
- Vehicle
- DMSO; final percentage not specified.
- Co-treatment
- None; single-agent TAE226 conditions selected.
- Reported limits
- No densitometric effect sizes or replicate count given for these blots. Figure 1 exposure time not specified in read sections; do not borrow S1 timing.
Methods and source locations
Compound reported in the paper: NVP-TAE226; Compound label in the paper: TAE226
Evidence concerns the named research compound; no equivalence of a tested batch to an Adooq lot is established.
Reagents; Western blot analysis; IGF-IR after serum-starvation methods; signaling Results; Figure 1 and S1
FAK Tyr397 and IGF-IR Tyr1131 phosphorylation: Figure 1 viewed; total FAK/IGF-IR and actin shown. — Figure 1 and signaling Results
IGF-IR signaling after starvation/stimulation: S1 viewed; IGF-I 100 ng/mL; total protein and unstimulated controls. No exact percent suppression inferred. — S1 Figure; IGF-IR after serum-starvation methods
