gdc-0834

InvivoChem Cat #:V4520CAS #:1133432-49-1Purity >=98%

Description: GDC-0834 (R-enantiomer) is a novel, potent and selective BTK inhibitor with an in vitro IC50 of 5.9 and 6.4 nM in biochemical and cellular assays, respectively, and in vivo IC50 of 1.1 and 5.6 uM in mouse and rat, respectively. Bruton's tyrosine kinase (BTK) plays a critical role in the development, differentiation, and proliferation of B-lineage cells, making it an attractive target for the treatment of rheumatoid arthritis. GDC-0834 inhibited BTK with an in vitro IC(50) of 5.9 and 6.4 nM in biochemical and cellular assays, respectively, and in vivo IC(50) of 1.1 and 5.6 uM in mouse and rat, respectively. Administration of GDC-0834 (30-100 mg/kg) in a rat collagen-induced arthritis (CIA) model resulted in a dose-dependent decrease of ankle swelling and reduction of morphologic pathology. An integrated disease progression pharmacokinetic/pharmacodynamic model where efficacy is driven by pBTK inhibition was fit to ankle-diameter time-course data. This model incorporated a transit model to characterize nondrug-related decreases in ankle swelling occurring at later stages of disease progression in CIA rats. The time course of ankle swelling in vehicle animals was described well by the base model. Simultaneous fitting of data from vehicle- and GDC-0834-treated groups showed that overall 73% inhibition of pBTK was needed to decrease the rate constant describing the ankle swelling increase (k(in)) by half. These findings suggest a high degree of pBTK inhibition is required for maximal activity of the pathway on inflammatory arthritis in rats.

References: J Pharmacol Exp Ther. 2011 Jul; 338(1):154-63; Drug Metab Dispos. 2015 Jun; 43(6):908-15.

Related CAS : 1133432-49-1 (R-enantiomer); 1133432-46-8 (GDC-0834 Racemate); 1133432-50-4 (GDC-0834 S-enantiomer)

-20C for 3 years in powder form

Synonym: GDC0834; GDC-0834; GDC 0834.
IUPAC/Chemical Name: (R)-N-(3-(6-((4-(1, 4-dimethyl-3-oxopiperazin-2-yl)phenyl)amino)-4-methyl-5-oxo-4, 5-dihydropyrazin-2-yl)-2-methylphenyl)-4, 5, 6, 7-tetrahydrobenzo[b]thiophene-2-carboxamide
InChi Key: CDOOFZZILLRUQH-GDLZYMKVSA-N
InChi Code: InChI=1S/C33H36N6O3S/c1-20-24(9-7-10-25(20)36-31(40)28-18-22-8-5-6-11-27(22)43-28)26-19-39(4)33(42)30(35-26)34-23-14-12-21(13-15-23)29-32(41)38(3)17-16-37(29)2/h7, 9-10, 12-15, 18-19, 29H, 5-6, 8, 11, 16-17H2, 1-4H3, (H, 34, 35)(H, 36, 40)/t29-/m1/s1
SMILES Code: O=C(C1=CC(CCCC2)=C2S1)NC3=CC=CC(C(N=C4NC5=CC=C([CH]6N(C)CCN(C)C6=O)C=C5)=CN(C)C4=O)=C3C