TP-422 (Negative control)
CECR2 (cat eye syndrome chromosome region, candidate 2) gene is predominantly expressed in the nervous system and involved in neurulation. It is located in the segment of chromosome 22q11.2. Multiplication of this segment lead to rare genetic disorder called cat eye syndrome characterized by multiple congenital defects (1). CECR2 has also been implicated in regulation of DNA damage response (2)
Bromodomain PHD finger transcription factor BPTF/FALZ is a core component of the conserved, multi-subunit nucleosome remodelling factor (NURF) complex. BPTF is essential for neural development and haematopoiesis (3). BPTF is involved in c-MYC chromatin recruitment and transcriptional activity in hematopetic and also cancer stem cells (4).
In a collaborative effort Takeda and the SGC have identified and characterised TP-238 as a CECR2/BPTF chemical probe.
Potency Against Target Family
TP-238 has on target biochemical activity of 10-30 nM with CECR2 and 100-350 nM with BPTF. Negative control TP-422 is completely inactive against BPTF and CECR2.
The closest off-target bromodomain inhibition is BRD9 with IC50 of 1.4 µM. TP-238 has been profiled against the panel of 338 kinases and showed no activity at 1 μM.
We recommend that TP-238 and TP-422 be used at no more than 2 µM concentration in cells.
Cell-based NanoBRETTM experiments measured the target engagement with both BPTF and CECR2 with EC50 in the 200-300 nM range.
In vitro Activity
TP-238 shows an IC50 of 30nM against CECR2 and 350nM against BPTF in an alphascreen assay. ITC shows TP-238 with a KD of 10nM for CECR2 and 120nM for BPTF.