Bartscht, Tobias published the artcileThe Src family kinase inhibitors PP2 and PP1 effectively block TGF-beta1-induced cell migration and invasion in both established and primary carcinoma cells, Category: indole-building-block, the publication is Cancer Chemotherapy and Pharmacology (2012), 70(2), 221-230, database is CAplus and MEDLINE.
Purpose: We have previously demonstrated that in pancreatic ductal adenocarcinoma (PDAC)-derived cell lines, the common Src family kinase inhibitors PP2 and PP1 effectively inhibited morphol. alterations associated with TGF尾1-mediated epithelial-to-mesenchymal transition (EMT) by blocking the kinase activity of the TGF-尾 type I receptor ALK5 rather than Src (Ungefroren et al. in Curr Cancer Drug Targets 11:524, 2011). In this report, the ability of PP2 and PP1, the more specific Src inhibitor SU6656, and the ALK5 inhibitor SB431542 to functionally block TGF-尾1-dependent EMT and cell motility in established PDAC (Panc-1, Colo 357) and primary NSCLC (Tu459) cell lines were investigated. Methods: The effects of PP2, PP1, SU6656, and SB431542 on TGF-尾1-dependent cell scattering/EMT, cell migration/invasion, and expression of invasion-associated genes were measured by using the real-time cell anal. assay on the xCELLigence system and quant. real-time RT-PCR, resp. Results: In all three cell lines tested, PP1, PP2, and SB431542 effectively blocked TGF-尾1-induced cell scattering/EMT, migration, and invasion and in Colo 357 cells inhibited the induction of the invasion-associated MMP2 and MMP9 genes. In contrast, SU6656 only blocked TGF-尾1-induced invasion in Panc-1 and Tu459 but not Colo 357 cells. PP1, and to a greater extent PP2, also inhibited the high spontaneous migratory activity of Panc-1 cells expressing a kinase-active ALK5 mutant. Conclusions: These data provide evidence that PP2 and PP1 are powerful inhibitors of TGF-尾-induced cell migration and invasion in vitro and directly target ALK5. Both agents may be useful as dual TGF-尾/Src inhibitors in exptl. therapeutics to prevent metastatic spread in late-stage PDAC and NSCLC.
Cancer Chemotherapy and Pharmacology published new progress about 330161-87-0. 330161-87-0 belongs to indole-building-block, auxiliary class Protein Tyrosine Kinase/RTK,Src, name is SU6656, and the molecular formula is C19H21N3O3S, Category: indole-building-block.
Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles