3-[5-[4-(2-hydroxy-2-methyl-1-oxopropyl)-1-piperazinyl]-2-(trifluoromethyl)phenyl]-4-(1H-indol-3-yl)-1H-pyrrole-2,5-dione

A potent, ATP-binding site targeting and reversible inhibitor of GSK-3, JAK3, PKCa and PKC (IC50 = 3, 8, 13 and 68 nM, respectively) with excellent selectivity over 40-kinases, including JAK1, JAK2 and Tyk2 (IC50 = 1.017, 2.55 and 8.055 µM, respectively). Shown to efficiently block interleukin stimulated STAT5 phosphorylation and T cell costimulation (IC50 = 0.525, 1.294 and 0.689 µM in IL15-MO7, IL2-CTLL and TCR/CD28-Jurkat cells, respectively)

OTAVAchemicals Catalogue Number: 7070707149
CAS Registry Number: 1260181-14-3
Purity: 97% (HPLC)

Ref. 1. Tsujimoto, Hiraku; Araoka, Toshikazu; Nishi, Yohei; Ohta, Akira; Nakahata, Tatsutoshi; Osafune, Kenji. Small molecule TCS21311 can replace BMP7 and facilitate cell proliferation in in vitro expansion culture of nephron progenitor cells. Biochemical and Biophysical Research Communications (2021), 558, 231-238;

Abstract: Several groups have developed in vitro expansion cultures for mouse metanephric nephron progenitor cells (NPCs) using cocktails of small molecules and growth factors including BMP7. However, the detailed mechanisms by which BMP7 acts in the NPC expansion remain to be elucidated. Here, by performing chemical screening for BMP substitutes, we identified a small molecule, TCS21311, that can replace BMP7 and revealed a novel inhibitory role of BMP7 in JAK3-STAT3 signaling in NPC expansion culture. Further, we found that TCS21311 facilitates the proliferation of mouse embryonic NPCs and human induced pluripotent stem cell-derived NPCs when added to the expansion culture. These results will contribute to understanding the mechanisms of action of BMP7 in NPC proliferation in vitro and in vivo and to the stable supply of NPCs for regenerative therapy, disease modeling and drug discovery for kidney diseases.

DOI:

10.1016/j.bbrc.2020.02.130