| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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Purity: ≥98%
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.
| 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].
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| 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].
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| References |
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| Molecular Formula |
C33H36N6O3S
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|---|---|
| Molecular Weight |
596.742345809937
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| Exact Mass |
596.256
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| CAS # |
1133432-49-1
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| Related CAS # |
GDC-0834 Racemate;1133432-46-8;GDC-0834 S-enantiomer;1133432-50-4
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| PubChem CID |
25234918
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.697
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| LogP |
3.68
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
43
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| Complexity |
1140
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1=C(C=CC=C1NC(=O)C2=CC3=C(S2)CCCC3)C4=CN(C(=O)C(=N4)NC5=CC=C(C=C5)[C@@H]6C(=O)N(CCN6C)C)C
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| InChi Key |
CDOOFZZILLRUQH-GDLZYMKVSA-N
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| 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
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| 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
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| Synonyms |
GDC0834; GDC-0834; GDC 0834.
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ≥ 32 mg/mL (~53.62 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| 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.
Calculation results
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.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 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.Drug Metab Dispos.2015 Jun;43(6):908-15. |
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 Homology model for aldehyde oxidase (AO) using the human sequence and the mouse crystal structure (PDB ID 3ZYV).
Formation of M1 after incubation of GDC-0834 (0.8µM) in (A) fresh whole blood and (B) plasma in human (○), rat ( |
 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).Drug Metab Dispos.2015 Jun;43(6):908-15. |
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COA
), mouse (▲), dog (♦), and monkey (●).