TP-008

2D structure
Target ACVR1B  TGFBR1 
Targeted domain Kinase domain (active site)
Mode of action Inhibitor (type 1, ATP competitive)
Control Al11
Recommended cellular usage concentration 1 - 10 µM
In vivo use No
Synonyms TGFbetaRI-IN-2
Donated by Takeda


Probe criteria


Inhibitor/agonist potency: goal is < 100 nM (IC50, Kd) Surpasses criterion: Lanthascreen (Takeda): TGFBR1 pIC50 = 7.6 and ACVR1B pIC50 = 6.0
Radioactive kinase assay (Reaction Biology): TGFBR1 pIC50 = 6.5 and ACVR1B pIC50 = 6.9
Selectivity within target family: > 30-fold Surpasses criterion: : Clean KINOMEscan; off targets > 20 µM in NanoBRET
Selectivity outside target family Closest off-targets: HTR2B 65% inhibition, PDE10A 73% inhibition (Diversity panel (Ricerca) results at 10 µM) .
Clean PDSP scan except for activity on HTR2B (70 % inhibition, Ki = 1881 nM)
On target cell activity for cell-based targets: goal is < 1 µM IC50/EC50 Surpasses criterion: ACVR1B IC50 = 526 ± 96 nM and TGFBR1 IC50 = 245 ± 41 nM in reporter gene assays; effects at 1 µM in WB on SMAD 2/3
Control compound (100 times less potent than the probe) Surpasses criterion: in vitro: > 10 µM (NanoBRET assay); Inactive in reporter gene assays, WB and kinome wide screen
One off-target in PDSP scan: HTR2B ( Ki = 1591.74 nM)