This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
Primary research
Qiaoyun Chu
Capital Medical University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-7344-0395
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Focal adhesion kinase (FAK), a multi-functional cytoplasmic tyrosine kinase, plays a critical role in cancer migration, proliferation and metastasis via regulating multiple signaling pathways. SY-707 is an ALK/FAK/IGF1R multi-kinase inhibitor and now evaluated in Phase II clinical trial for ALK positive non-small cell lung cancer (NSCLC).
Methods
HTRF (Homogeneous Time-Resolved Fluorescence) assay was used to analyze kinase enzyme activity to determine inhibitory activities of SY-707 on other kinases. ATP content, PE-Annexin V and would healing assays were used to examine cell proliferation, cell cycle and migration when cells were treated with SY707. Then, SD rat and beagle dog models were used to evaluate the pharmacokinetics profile, and mouse xenograft model was used to evaluate the in vivo anti-cancer activities of SY707.
Results
In this study, we assessed preclinical anti-growth and anti-metastasis potency of SY-707 in breast cancer cells. SY-707 was able to inhibit the growth of breast cancer cell lines and induced cell apoptosis by suppressing the FAK signaling pathways. Moreover, SY-707 exerted inhibition on cell migration and adhesion in a dose-dependent manner. In T47D xenograft mice, SY-707 had significant anti-tumor activities lonely or synergistically with Paclitaxel. Meanwhile, SY-707 also displayed significant suppression on spontaneous metastasis of tumor to the lung in 4T1 murine breast cancer xenograft model.
Conclusions
SY-707 illustrated potent anti-proliferation and anti-migration potential in breast cancer in vitro and in vivo, implying its therapeutic application for the treatment of breast cancer in future clinical trials.
Keywords
SY-707, anti-tumor, anti-metastasis, breast cancer
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Loading...
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
View the published article at Acta Biochimica et Biophysica Sinica.
No community comments so far
Version 1
Posted 20 Jan, 2021
No comments provided
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Learn more about our company.
A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Primary research
Qiaoyun Chu
Capital Medical University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-7344-0395
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
View the published article at Acta Biochimica et Biophysica Sinica.
No community comments so far
Version 1
Posted 20 Jan, 2021
No comments provided
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Acta Biochimica et Biophysica Sinica.
Background
Focal adhesion kinase (FAK), a multi-functional cytoplasmic tyrosine kinase, plays a critical role in cancer migration, proliferation and metastasis via regulating multiple signaling pathways. SY-707 is an ALK/FAK/IGF1R multi-kinase inhibitor and now evaluated in Phase II clinical trial for ALK positive non-small cell lung cancer (NSCLC).
Methods
HTRF (Homogeneous Time-Resolved Fluorescence) assay was used to analyze kinase enzyme activity to determine inhibitory activities of SY-707 on other kinases. ATP content, PE-Annexin V and would healing assays were used to examine cell proliferation, cell cycle and migration when cells were treated with SY707. Then, SD rat and beagle dog models were used to evaluate the pharmacokinetics profile, and mouse xenograft model was used to evaluate the in vivo anti-cancer activities of SY707.
Results
In this study, we assessed preclinical anti-growth and anti-metastasis potency of SY-707 in breast cancer cells. SY-707 was able to inhibit the growth of breast cancer cell lines and induced cell apoptosis by suppressing the FAK signaling pathways. Moreover, SY-707 exerted inhibition on cell migration and adhesion in a dose-dependent manner. In T47D xenograft mice, SY-707 had significant anti-tumor activities lonely or synergistically with Paclitaxel. Meanwhile, SY-707 also displayed significant suppression on spontaneous metastasis of tumor to the lung in 4T1 murine breast cancer xenograft model.
Conclusions
SY-707 illustrated potent anti-proliferation and anti-migration potential in breast cancer in vitro and in vivo, implying its therapeutic application for the treatment of breast cancer in future clinical trials.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Loading...