PRN 1008
Names
[ CAS No. ]:
1575596-29-0
[ Name ]:
PRN 1008
Biological Activity
[Description]:
PRN1008 is a reversible covalent inhibitor of Bruton’s Tyrosine Kinase (BTK), with an IC50 of 1.3 nM.
[Related Catalog]:
[Target]
BTK:1.3 nM (IC50)
BMX:1.0 nM (IC50)
ITK:440 nM (IC50)
TEC:0.8 nM (IC50)
RLK:1.2 nM (IC50)
BLK:6.3 nM (IC50)
EGFR:520 nM (IC50)
ERBB2:3900 nM (IC50)
ERBB4:11.3 nM (IC50)
[In Vitro]
PRN1008 is a reversible covalent inhibitor of Bruton’s Tyrosine Kinase (BTK), with an IC50 of 1.3±0.5 nM. PRN1008 is also found to be highly selectively when tested in a panel of 251 other kinases. Cysteine targeting of BTK by PRN1008 results in a slow off-rate demonstrated by retention of 79±2% of binding to BTK in PBMC 18 hours after washing away the compound in vitro. The covalent cysteine binding is completely reversible after denaturation of the target. Anti-IgM induces human B cell proliferation (10% serum) and B cell CD69 expression are inhibited by PRN1008 with IC50 of 5±2.4 nM and 123±38 nM, respectively[2].
[In Vivo]
In vivo PRN1008 demonstrates enduring pharmacodynamic effects after the compound has cleared from circulation, consistent with extended target residence time. PRN1008 also reverses and completely suppresses collagen-induced arthritis in rats in a dose dependent manner which allows correlation of target occupancy and disease modification[2].
[References]
[Related Small Molecules]
Acalabrutinib
|
GDC-0853
|
Evobrutinib
|
AVL-292
|
(±)-Zanubrutinib
|
ONO-4059
|
BMX-IN-1
|
GDC-0834
|
SNS-062
|
RN486
|
LFM-A13
|
Vecabrutinib
|
CGI-1746
|
BMS-986195
|
CNX-774
Chemical & Physical Properties
[ Molecular Formula ]:
C36H40FN9O3
[ Molecular Weight ]:
665.76
[ Storage condition ]:
2-8℃