In PC-3 cells, the proliferation assay showed 20.5 ± 3.9% and 64.8 ± 0.1% inhibition at 3 and 10 μM, respectively, after 4 days (mean ± SD). In a separate 72 h suspension assay, BMS-777607 did not significantly increase anoikis at 10 μM (P = 0.13), although wortmannin increased cell death. MET phosphorylation suppression therefore did not translate into uniform effects across these cellular endpoints. [1]
In serum-starved MDA-MB231 cells, 50 ng/ml NRG1 compensated the viability inhibition produced by 0.1 or 1 μM BMS-777607 over 72 h. Rescue was incomplete at 10 μM. This ligand-dependent response limits interpretation of single-agent activity in that model. [2]
In T-47D and ZR-75-1 breast cancer cells, 72 h pretreatment with 5 μM BMS-777607 increased residual viability during subsequent cisplatin, paclitaxel or doxorubicin exposure. Including 25 nM AZD8055 during pretreatment restored sensitivity toward control levels. This was a sequential cell-culture assay and does not establish clinical benefit or direct synergy between the two inhibitors. [3]
Cellular inhibition of constitutive MET signaling
Cell-based study · Human prostate cancer PC-3 cells [1]
BMS-777607 suppressed MET Y1234/1235 phosphorylation. Downstream responses varied by site and time: FAK Y397 remained largely unchanged, whereas Src Y416 and FAK Y861 decreased; Akt/mTOR pathway inhibition developed during prolonged exposure.
Literature-Reported Treatment Conditions
- Treatment concentration
- 0, 0.1, 0.5, 1, 5 and 10 μM (1 h dose series); 1 μM (time series)
- Exposure duration
- 1 h dose series; 0, 1, 3 and 24 h time series
- Method
- Exposure followed by whole-cell Western blot
- Vehicle
- DMSO used to dissolve powder; final solvent fraction and explicit matching of the 0-dose lane are not specified in the read Methods.
- Reported limits
- No kinase-binding assay or intracellular target occupancy measurement; final DMSO percentage unreported.
Methods and source locations
Compound reported in the paper: BMS-777607; Compound label in the paper: BMS-777607
Literature evidence for named BMS-777607; salt/solvate and lot equivalence are not established. No Adooq lot validation.
Figure 6A–B; Results, BMS-777607 blocked constitutive c-Met signaling; Methods, Reagents and antibodies / Western blot
MET Y1234/1235 phosphorylation: Immunoblot; total MET and actin controls; representative of 2 independent experiments — Figure 6A; corresponding Results paragraph
Site- and time-dependent downstream signaling: Immunoblot with actin loading control; representative of 2 independent experiments — Figure 6A–B; corresponding Results paragraph
PC-3 proliferation response
Cell-based study · Human prostate cancer PC-3 cells [1]
Substantial inhibition of the proliferation assay required micromolar concentrations, despite suppression of MET phosphorylation at lower concentrations in the separate signaling experiment.
Literature-Reported Treatment Conditions
- Treatment concentration
- 0, 0.3, 1, 3 and 10 μM
- Exposure duration
- 4 days (96 h)
- Method
- WST-8 metabolic proliferation assay; untreated control normalization
- Vehicle
- DMSO stock; final solvent percentage not specified
- Reported limits
- Metabolic endpoint does not independently establish cell count or apoptosis.
Methods and source locations
Compound reported in the paper: BMS-777607; Compound label in the paper: BMS-777607
Literature evidence for named BMS-777607; salt/solvate and lot equivalence are not established. No Adooq lot validation.
Figure 5A; Results, PC-3 was responsive to the small molecule Met kinase inhibitor; Methods, Cell proliferation
Inhibition of proliferation relative to untreated control: 96 h WST-8 assay described as MTT by authors; Figure 5A mean ± SD, n ≥9; data from >3 independent experiments — Figure 5A and corresponding Results paragraph; Methods, Cell proliferation
Limited effect on anchorage-independent cell death
Cell-based study · Suspended human prostate cancer PC-3 cells [1]
BMS-777607 did not significantly increase anoikis under the tested conditions; the PI3K inhibitor wortmannin increased cell death as an assay comparator.
Literature-Reported Treatment Conditions
- Treatment concentration
- BMS-777607: 0, 1, 3 and 10 μM; separate wortmannin comparator: 0.1 μM
- Exposure duration
- 3 days (72 h)
- Method
- Poly-HEMA suspension culture and trypan blue exclusion
- Vehicle
- DMSO stock; final solvent percentage not specified
- Co-treatment
- None; wortmannin is a separate comparator, not a combination treatment.
- Reported limits
- Failure to reach significance does not establish equivalence or absence of every survival effect.
Methods and source locations
Compound reported in the paper: BMS-777607; Compound label in the paper: BMS-777607
Literature evidence for named BMS-777607; salt/solvate and lot equivalence are not established. No Adooq lot validation.
Figure 5F; Results paragraph following Figure 5; Methods, Anoikis
Trypan-blue-positive cell death during suspension culture: 72 h trypan blue exclusion; mean ± SD, n ≥9; >3 independent experiments; Student’s t-test — Figure 5F and corresponding Results paragraph
Cellular AXL phosphorylation concentration response
Cell-based study · Axl-overexpressing NIH/3T3-Axl cells [2]
BMS777607 inhibited AXL phosphorylation in a cell-based phosphotyrosine ELISA. The reported IC50 describes this cellular phosphorylation endpoint.
Literature-Reported Treatment Conditions
- Treatment concentration
- Serially diluted concentrations; Figure 1A displays 0.001–1 μM
- Exposure duration
- 1 h treatment after 24 h starvation
- Method
- Cell-based phospho-AXL ELISA
- Vehicle
- DMSO stock; final solvent fraction and assay baseline normalization details not specified in the read ELISA subsection.
- Reported limits
- No uncertainty interval or independent-experiment count for this specific IC50 stated in the read caption. This is not a cell-free biochemical potency.
Methods and source locations
Compound reported in the paper: BMS-777607; Compound label in the paper: BMS777607
Literature evidence for named BMS-777607; salt/solvate and lot equivalence are not established. No Adooq lot validation.
Figure 1A (also described in Figure 2A caption); Results opening paragraph; Methods, Phospho-Axl ELISA / Inhibitors and monoclonal antibodies
Inhibition of AXL phosphorylation: 1 h treatment followed by phospho-tyrosine AXL ELISA; four-parameter logistic fit — Figure 1A caption; Results opening Axl validation paragraph
NRG1 rescue of the cellular viability response
Cell-based study · Human breast cancer MDA-MB231 cells under serum starvation (0% FBS) [2]
NRG1 compensated the viability inhibition seen with 0.1 and 1 μM BMS777607. At 10 μM, rescue was incomplete in the viewed figure; the DMSO control did not show an NRG1-dependent viability increase.
Literature-Reported Treatment Conditions
- Treatment concentration
- BMS777607: 0.1, 1 and 10 μM; NRG1: 50 ng/ml
- Exposure duration
- 72 h
- Method
- CellTiter-Glo ATP-based viability assay under 0% FBS
- Vehicle
- DMSO control, tested with and without NRG1; final DMSO fraction unspecified
- Co-treatment
- BMS777607 with or without NRG1; NRG1 is an exogenous ligand, not a cytotoxic drug.
- Reported limits
- No exact viability percentages extracted from bars. Applicability outside this starvation/ligand context not established.
Methods and source locations
Compound reported in the paper: BMS-777607; Compound label in the paper: BMS777607
Literature evidence for named BMS-777607; salt/solvate and lot equivalence are not established. No Adooq lot validation.
Figure 6A; Results, Exogenous Application of NRG1 Rescues AKT Phosphorylation and Cell Viability; Methods, Cell Viability
Viability with and without NRG1 during BMS777607 exposure: CellTiter-Glo after 72 h; means ± SEM of 3 independent experiments; Mann–Whitney comparisons in caption — Figure 6A image/caption and corresponding Results paragraph
Sequential pretreatment alters chemotherapy sensitivity
Cell-based study · Human breast cancer T-47D and ZR-75-1 cells [3]
Relative to the corresponding control pretreatment, BMS-777607 pretreatment increased residual viability after cisplatin, paclitaxel or doxorubicin challenge in both lines. Adding AZD8055 during pretreatment restored responses toward chemoagent-only controls. This sequential assay is distinct from direct synergy of BMS-777607 and AZD8055.
Literature-Reported Treatment Conditions
- Treatment concentration
- Pretreatment: 5 μM BMS-777607, 25 nM AZD8055, their combination, or neither. Challenge in T-47D: 3.7 μM cisplatin, 4 nM paclitaxel or 300 nM doxorubicin; in ZR-75-1: 1.6 μM cisplatin, 6 nM paclitaxel or 450 nM doxorubicin.
- Exposure duration
- 72 h pretreatment followed by 72 h chemoagent challenge after viable-cell collection and replating
- Method
- RPMI-1640 with 5% FBS; MTS viability assay with pretreatment-specific baselines
- Vehicle
- Vehicle identity/fraction not specified for Table 1 in the read text.
- Co-treatment
- AZD8055 is combined with BMS-777607 during pretreatment; chemoagents are tested as subsequent separate challenges.
- Reported limits
- Shared statistical Methods 2.7 defines mean ± SD. Table 1 does not specify the number of independent experiments; triplicate plating is explicit. Exact tabulated percentages and sensitivity indices are not adopted.
Methods and source locations
Compound reported in the paper: BMS-777607; Compound label in the paper: BMS-777607
Literature evidence for named BMS-777607; salt/solvate and lot equivalence are not established. No Adooq lot validation.
Table 1 (all rows and footnote); Results 3.6; Methods 2.1 and 2.6
Residual viability after chemoagent challenge: MTS after sequential 72 h pretreatment and 72 h chemoagent exposure; replated viable cells in triplicate; each pretreatment baseline set to 100% — Table 1, T-47D and ZR-75-1 treatment rows and footnote
