GDC-0834

Alias: GDC0834; GDC-0834; GDC 0834.
Cat No.:V4520 Purity: ≥98%
GDC-0834 (R-enantiomer) is a novel, potent and selectiveBTKinhibitor with an in vitroIC50of 5.9 and 6.4 nM in biochemical and cellular assays, respectively, and in vivoIC50of 1.1 and 5.6 μM in mouse and rat, respectively.
GDC-0834 Chemical Structure CAS No.: 1133432-49-1
Product category: New7
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
5mg
10mg
Other Sizes

Other Forms of GDC-0834:

  • GDC-0834 Racemate
  • GDC-0834 S-enantiomer
Official Supplier of:
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Purity & Quality Control Documentation

Purity: ≥98%

Product 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 μM 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 μM 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.

Biological Activity I Assay Protocols (From Reference)
ln Vitro
With an IC50 value of 5.9±1.1 nM and a Hill slope value of -0.84±0.07 (mean±SE), GDC-0834 inhibits BTK kinase activity [1]. With IC50 values ranging from 0.86 to 1.87 μM, GDC-0834 was demonstrated to be a strong and reversible inhibitor of six recognized aldehyde oxidase (AO) substrates[2].
ln Vivo
GDC-0834 treatment of BALB/c mice led to pBTK-Tyr223 inhibition in a dose-dependent manner. The blood levels of pBTK-Tyr223 were completely inhibited in animals given 150 or 100 mg/kg GDC-0834 for two hours, with average inhibition rates of 97% and 96%, respectively. GDC-0834 suppressed pBTK-Tyr223 in rat blood in a dose-dependent manner in a research on CIA rats. Rats' estimated IC50 for pBTK-Tyr223 inhibition is 5.6±1.6 μM, with a mean±standard error of 0.51±0.087 [1].
References
[1]. Liu L, et al. Antiarthritis effect of a novel Bruton's tyrosine kinase (BTK) inhibitor in rat collagen-induced arthritis and mechanism-based pharmacokinetic/pharmacodynamic modeling: relationships between inhibition of BTK phosphorylation and efficacy. J
[2]. Sodhi JK, et al. A novel reaction mediated by human aldehyde oxidase: amide hydrolysis of GDC-0834. Drug Metab Dispos. 2015 Jun;43(6):908-15
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C33H36N6O3S
Molecular Weight
596.742345809937
CAS #
1133432-49-1
SMILES
O=C(C1=CC(CCCC2)=C2S1)NC3=CC=CC(C(N=C4NC5=CC=C([C@H]6N(C)CCN(C)C6=O)C=C5)=CN(C)C4=O)=C3C
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
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
Synonyms
GDC0834; GDC-0834; GDC 0834.
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO : ≥ 32 mg/mL (~53.62 mM)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 1.6758 mL 8.3789 mL 16.7577 mL
5 mM 0.3352 mL 1.6758 mL 3.3515 mL
10 mM 0.1676 mL 0.8379 mL 1.6758 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

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Biological Data
  • GDC-0834


    Proteomic correlation profiling revealed that aldehyde oxidase (AO/ADO) is an enzyme present in cytosolic fractions containing the hydrolytic enzyme activity involved in the metabolism of GDC-0834.2015 Jun;43(6):908-15.

  • GDC-0834


    Homology model for aldehyde oxidase (AO) using the human sequence and the mouse crystal structure (PDB ID 3ZYV).

    GDC-0834

    Formation of M1 after incubation of GDC-0834 (0.8µM) in (A) fresh whole blood and (B) plasma in human (○), rat (GDC-0834), mouse (▲), dog (♦), and monkey (●).

  • GDC-0834


    IC50curves for the inhibition by GDC-0834 (0–50 or 0–100μM) of AO-mediated metabolism of AO probe substrates in human liver cytosol (A) carbazeran (formation of 4-hydroxycarbazeran), (B) DACA (formation of DACA-9(10H)-acridone), (C)O6-benzylguanine (formation of 8-oxobenzylguanine), (D) phthalazine (formation of phthalazinone), (E) zaleplon (formation of 5-oxozaleplon), and (F) zoniporide (formation of 2-oxozoniporide).2015 Jun;43(6):908-15.

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