Designation | Y551 Sequestration | Averaged B’ for Y551a | rBtk WT/ Y551E | Whole-Blood FcεR/BCR | Ramos pY551/ pY223b | RBL-2H3 pY551/ pY223b |
---|---|---|---|---|---|---|
GDC-0834 | Yes | −0.35 | 0.03 | 1.11 | 1 | 0.01 |
CGI1746 | Yes | −0.63 | 0.01 | 1.60 | 1 | 0.1 |
RN486 | Yes | 0.26 | 0.15 | 1.46 | 1 | 0.01 |
RN983 | Yes | −0.27 | 0.02 | 1.32 | 1 | 0.1 |
Ibrutinib-Rev | No | 2.22 | 0.29 | 2.55 | 100 | 100 |
Ibrutinib | No | 3.08 | 0.40 | 22.86 | 10,000 | 100 |
CNX 774 | No | 2.51 | 0.29 | 3.63 | 100 | 1000 |
CC 292 | No | Absent | 0.80 | 6.83 | 1000 | 100 |
ONO-4059 | No | 2.64 | 0.57 | 27.08 | 10,000 | 10 |
↵a The averaged B factor for the atoms in the Y551 residue was determined from the crystal structure of the compound in complex with Y551. The term absent is used when the mobility of the residues was too great for it to be accurately localized in the determined structure.
↵b The ratio of the IC50 for inhibition of Btk pY551 to Btk pY223 was calculated by dividing the values determined for pY551 by pY223 (as described in Fig. 3).