Stressor: 642

Title

To create a new stressor, from the Listing Stressors page at https://aopwiki.org/stressors click ‘New stressor.’ This will bring you to a page entitled “New Stressor” where a stressor title can be entered. Click ‘Create stressor’ to create a new Stressor page listing the stressor title at the top. More help

Saracatinib

Stressor Overview

The stressor field is a structured data field that can be used to annotate an AOP with standardised terms identifying stressors known to trigger the MIE/AOP. Most often these are chemical names selected from established chemical ontologies. However, depending on the information available, this could also refer to chemical categories (i.e., groups of chemicals with defined structural features known to trigger the MIE). It can also include non-chemical stressors such as genetic or environmental factors. More help

AOPs Including This Stressor

This table is automatically generated and lists the AOPs associated with this Stressor. More help

Events Including This Stressor

This table is automatically generated and lists the Key Events associated with this Stressor. More help
Event Name
Inhibition of Fyna

Chemical Table

The Chemical Table lists chemicals associated with a stressor. This table contains information about the User’s term for a chemical, the DTXID, Preferred name, CAS number, JChem InChIKey, and Indigo InChIKey.To add a chemical associated with a particular stressor, next to the Chemical Table click ‘Add chemical.’ This will redirect you to a page entitled “New Stressor Chemical.’ The dialog box can be used to search for chemical by name, CAS number, JChem InChIKey, and Indigo InChIKey. Searching by these fields will bring forward a drop down list of existing stressor chemicals formatted as  Preferred name, “CAS- preferred name,” “JChem InChIKey – preferred name,” or “Indigo InChIKey- preferred name,” depending on by which field you perform the search. It may take several moments for the drop down list to display. Select an entity from the drop down list and click ‘Add chemical.’ This will return you to the Stressor Page, where the new record should be in the ‘Chemical Table’ on the page.To remove a chemical associated with a particular stressor, in the Chemical Table next to the chemical you wish to delete, click ‘Remove’ and then click 'OK.' The chemical should no longer be visible in the Chemical table. More help
User term DTXID Preferred name Casrn jchem_inchi_key indigo_inchi_key
Saracatinib DTXSID90191355 Saracatinib 379231-04-6 OUKYUETWWIPKQR-UHFFFAOYSA-N OUKYUETWWIPKQR-UHFFFAOYSA-N

AOP Evidence

This table is automatically generated and includes the AOPs with this associated stressor as well as the evidence term and evidence text from this AOP Stressor. More help

Event Evidence

This table is automatically generated and includes the Events with this associated stressor as well as the evidence text from this Event Stressor. More help
Inhibition of Fyna

Dual SFK inhibitors (e.g., dasatinib, bosutinib and saracatinib) already approved for therapy or are in clinical trials (Musumeci et al., 2012). Saracatinib (AZD0530) is a small molecule inhibitor of Src family kinases, inhibiting Src, Fyna, Yes and Lyn, with 2 to 10 nM potency. AZD0530 specific inhibition of Fyna and other SFKs has led to its development as therapy for solid tumors, because Src family kinases regulate tumor cell adhesion, migration and invasion, and also regulate proliferation (Hennequin et al., 2006). AZD0530 has numerous desirable properties. For example, AZD0530 inhibits Fyna activity in the low nM range (Green et al., 2009) has a half‐life of 16 hours in the mouse and is highly brain penetrable (Kaufman et al., 2015).

Stressor Info

Text sections under this subheading include the Chemical/Category Description and Characterization of Exposure. More help
Chemical/Category Description
To edit the Chemical/Category Description” section, on a KER page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing Stressor.”  Scroll down to the “Chemical/Category Description” section, where a text entry box allows you to submit text. Click ‘Update’ to save your changes and return to the Stressor page.  The new text should appear under the “Chemical/Category Description”  section on the page. More help
Characterization of Exposure
To edit the “Characterization of Exposure” section, on a Stressor page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing Stressor.”  Scroll down to the “Characterization of Exposure”  section, where a text entry box allows you to submit text. Click ‘Update’ to save your changes and return to the Stressor page.  The new text should appear under the “Characterization of Exposure” section on the page. More help

References

List of the literature that was cited for this Stressor description. Ideally, the list of references, should conform, to the extent possible, with the OECD Style Guide (https://www.oecd.org/about/publishing/OECD-Style-Guide-Third-Edition.pdf) (OECD, 2015).To edit the “References” section, on a Stressor page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing Stressor.”  Scroll down to the “References” section, where a text entry box allows you to submit text. Click ‘Update’ to save your changes and return to the Stressor page.  The new text should appear under the “References” section on the page. More help

Musumeci, F., Schenone, S., Brullo, C., & Botta, M. (2012). An update on dual Src/Abl inhibitors. Future Medicinal Chemistry, 4(6), 799–822. https://doi.org/10.4155/fmc.12.29

Hennequin, L. F., Allen, J., Breed, J., Curwen, J., Fennell, M., Green, T. P., Lambert-Van Der Brempt, C., Morgentin, R., Norman, R. A., Olivier, A., Otterbein, L., Plé, P. A., Warin, N., & Costello, G. (2006). N-(5-chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy] -5-(tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine, a novel, highly selective, orally available, dual-specific c-Src/Abl kinase inhibitor. Journal of Medicinal Chemistry, 49(22), 6465–6488. https://doi.org/10.1021/jm060434q

Green, T. P., Fennell, M., Whittaker, R., Curwen, J., Jacobs, V., Allen, J., Logie, A., Hargreaves, J., Hickinson, D. M., Wilkinson, R. W., Elvin, P., Boyer, B., Carragher, N., Plé, P. A., Bermingham, A., Holdgate, G. A., Ward, W. H. J., Hennequin, L. F., Davies, B. R., & Costello, G. F. (2009). Preclinical anticancer activity of the potent, oral Src inhibitor AZD0530. Molecular Oncology, 3(3), 248–261. https://doi.org/10.1016/j.molonc.2009.01.002

Kaufman, A. C., Salazar, S. V, Haas, L. T., Yang, J., Kostylev, M. A., Jeng, A. T., Robinson, S. A., Gunther, E. C., Van Dyck, C. H., Nygaard, H. B., Strittmatter, S. M., & Author, A. N. (2015). Fyn Inhibition Rescues Established Memory and Synapse Loss in Alzheimer Mice HHS Public Access Author manuscript. Ann Neurol, 77(6), 953–971. https://doi.org/10.1002/ana.24394