Fenebrutinib (GDC-0853) is a potent, selective, non-covalent BTK inhibitor with a Ki value of 0.91 nM for BRK. The IC50 value of BTK was more than 100 times that of the other three off-target kinases. (Bmx: 153x, Fgr: 168x, Src: 131x).

 

Brand: BCM

 

Target: BTK

 

Signaling Pathways: Angiogenesis; Tyrosine Kinase/Adaptors

 

In Vitro: Biochemical screening with 1 μM GDC-0853 in a broad-spectrum human kinase library showed that GDC-0853 inhibited only 3 of 286 off-target kinases, and the selectivity/efficacy of GDC-0853 against BTK was much greater than that against these three kinases (Bmx, Fgr, Src). GDC-0853 can inhibit BCR signal in B cells and FcγR signal in monocytes. The average residence time of GDC-0853 combined with BTK was 18.3 ± 2.8 hours. GDC-0853 can inhibit the autophosphorylation of WT BTK and C481S mutants in cells. In vitro, when chronic lymphocytic leukemia cells were treated with GDC-0853 and then stimulated with BCR signaling, GDC-0853 treatment reduced the level of BTK phosphorylation and weakened the activation of downstream targets such as PLCγ2, AKT, and ERK. GDC-0853 inhibits NF-κB-dependent transcription, reduces its activation, and prevents cell migration. In the cell, GDC-0853 has no inhibitory effect on EGFR and ITK, nor does it affect the activation of T cell receptors.

 

Boiling Point: 936.3±65.0 °C(Predicted)

 

pKa: 13.15±0.10(Predicted)

 

Solubility: Soluble in DMSO. Insoluble in Water; Insoluble in Ethanol.

 

Isomeric SMILES: C[C@H]1CN(CCN1C2=CN=C(C=C2)NC3=CC(=CN(C3=O)C)C4=C(C(=NC=C4)N5CCN6C7=C(CC(C7)(C)C)C=C6C5=O)CO)C8COC8  

 

InChIKey: WNEODWDFDXWOLU-QHCPKHFHSA-N  

 

InChI: InChI=1S/C37H44N8O4/c1-23-18-42(27-21-49-22-27)9-10-43(23)26-5-6-33(39-17-26)40-30-13-25(19-41(4)35(30)47)28-7-8-38-34(29(28)20-46)45-12-11-44-31(36(45)48)14-24-15-37(2,3)16-32(24)44/h5-8,13-14,17,19,23,27,46H,9-12,15-16,18,20-22H2,1-4H3,(H,39,40)/t23-/m0/s1

 

Attribute
[Chem Name]	10-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2S)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-4,4-dimethyl-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-9-one
[Synonym]	Fenebrutinib; GDC-0853
[CAS No.]	1434048-34-6
[MDL No.]	MFCD30489729
[Formula]	C37H44N8O4
[Molecular]	664.8
[Form]	Solid Powder
[Storage]	Keep in dark place. Sealed in dry, 2-8°C

Goods Tag