| Title: |
Next Generation Potent Cell‐active Inhibitors of the Oncogenic PTP4A3 Phosphatase |
| Authors: |
Blanco, Isabella K.; Tasker, Nikhil R.; Rastelli, Etttore J.; Wipf, Peter; Sharlow, Elizabeth R.; Lazo, John S. |
| Contributors: |
U.S. Department of Defense; National Institutes of Health |
| Source: |
The FASEB Journal ; volume 33, issue S1 ; ISSN 0892-6638 1530-6860 |
| Publisher Information: |
Wiley |
| Publication Year: |
2019 |
| Collection: |
Wiley Online Library (Open Access Articles via Crossref) |
| Description: |
High grade serous ovarian cancer and triple negative breast cancer respond poorly to existing drugs and, thus, demand new therapies. The protein tyrosine phosphatase PTP4A3 (Phosphatase of Regenerating Liver‐3, PRL‐3) is overexpressed in these diseases. Moreover, PTP4A3 promotes cancer cell migration and invasion and is believed to be the most oncogenic of all tyrosine phosphatases. We recently synthesized the novel iminothienopyridone, JMS‐053, and demonstrated that it is a specific, reversible, allosteric, and cell active small molecule PTP4A3 inhibitor with an in vitro IC 50 for PTP4A3 of 30 nM. The water solubility of JMS‐053 is limited, however. Therefore, we synthesized twenty next generation analogs to improve aqueous solubility and to aid in determining the structure activity relationship for the chemotype, the PTP4A3 binding site, and the mechanism of inhibition. Seventeen analogs retained potent in vitro PTP4A3 inhibition with IC 50 values |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1096/fasebj.2019.33.1_supplement.674.11 |
| Availability: |
https://doi.org/10.1096/fasebj.2019.33.1_supplement.674.11 |
| Rights: |
http://onlinelibrary.wiley.com/termsAndConditions#am ; http://onlinelibrary.wiley.com/termsAndConditions#vor |
| Accession Number: |
edsbas.3F51195F |
| Database: |
BASE |