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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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500mg |
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Other Sizes |
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Purity: ≥98%
Fenebrutinib HCl (formerly known RG-7845; GDC-0853 hydrochloride) is an orally bioavailable, and noncovalent (reversible) bruton's tyrosine kinase (BTK) inhibitor (Ki = 0.91 nM) with anticancer and anti-inflammatory activity. It is in development for the treatment of rheumatoid arthritis and systemic lupus erythematosus. In Sprague-Dawley (SD) rats, administration of GDC-0853 and other structurally diverse BTK inhibitors for 7 days or longer caused pancreatic lesions consisting of multifocal islet-centered hemorrhage, inflammation, fibrosis, and pigment-laden macrophages with adjacent lobular exocrine acinar cell atrophy, degeneration, and inflammation. Similar findings were not observed in mice or dogs at much higher exposures. Hemorrhage in the peri-islet vasculature emerged between four and seven daily doses of GDC-0853 and was histologically similar to spontaneously occurring changes in aging SD rats. This suggests that GDC-0853 could exacerbate a background finding in younger animals. Glucose homeostasis was dysregulated following a glucose challenge; however, this occurred only after 28 days of administration and was not directly associated with onset or severity of pancreatic lesions. There were no changes in other common serum biomarkers assessing endocrine and exocrine pancreatic function. Additionally, these lesions were not readily detectable via Doppler ultrasound, computed tomography, or magnetic resonance imaging. These results indicate that pancreatic lesions in rats are likely a class effect of BTK inhibitors, which may exacerbate an islet-centered pathology that is unlikely to be relevant to humans. Bruton's tyrosine kinase (BTK) is a member of the Tec family of cytoplasmic tyrosine kinases involved in B-cell and myeloid cell signaling.
Molecular Formula |
C37H45CLN8O4
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Molecular Weight |
701.26
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CAS # |
2128304-54-9
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Related CAS # |
1434048-34-6;2128304-54-9 (HCl);2128304-53-8 (mesylate);2128304-55-0 (sulfate);
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Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
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SMILES |
O=C1C(N2CCN1C3=NC=CC(C(C=C4NC5=NC=C(N6[C@@H](C)CN(C7COC7)CC6)C=C5)=CN(C)C4=O)=C3CO)=CC8=C2CC(C)(C)C8.[H]Cl
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InChi Key |
UFNQEETXQCTBNF-BQAIUKQQSA-N
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InChi Code |
InChI=1S/C37H44N8O4.ClH/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);1H/t23-;/m0./s1
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Chemical Name |
(S)-2-(3'-(hydroxymethyl)-1-methyl-5-((5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)amino)-6-oxo-1,6-dihydro-[3,4'-bipyridin]-2'-yl)-7,7-dimethyl-3,4,7,8-tetrahydro-2H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1(6H)-one hydrochloride
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Synonyms |
RG-7845 HCl; GDC-0853 HCl; RG7845 HCl; GDC 0853; RG 7845 hydrochloride; GDC0853 HCl
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 1.4260 mL | 7.1300 mL | 14.2600 mL | |
5 mM | 0.2852 mL | 1.4260 mL | 2.8520 mL | |
10 mM | 0.1426 mL | 0.7130 mL | 1.4260 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.
Representative photomicrographs of pancreatic histopathology observed in Sprague-Dawley rats following daily oral administration of GDC-0853 for 21 or 28 days are presented.J Pharmacol Exp Ther. 2017 Jan;360(1):226-238. td> |
Exposure to GDC-0853 in Sprague-Dawley rats relative to BTK (on-target) and off-target (BMX, FGR, SRC) kinase half-maximal inhibitory concentrations (IC50) is presented. Strain sensitivity to BTK inhibitor–induced pancreatic lesions is presented.J Pharmacol Exp Ther. 2017 Jan;360(1):226-238. td> |
Relative Btk transcript expression (dCT; delta Cycle Threshold) in pancreatic tissue from humans and Sprague-Dawley rats is presented. Glucose and insulin levels in Sprague-Dawley rats following administration of GDC-0853 are presented.J Pharmacol Exp Ther. 2017 Jan;360(1):226-238. td> |
Amylase, lipase, insulin, and fructosamine levels in Sprague-Dawley rats (n≤ 15 per sex per group) following administration of GDC-0853 are presented.J Pharmacol Exp Ther. 2017 Jan;360(1):226-238. td> |
Ultrasound imaging of the pancreas in Sprague-Dawley rats following administration of GNE-309 (n= 8 males per group) or GDC-0853 (n= 16 males per group) is presented.J Pharmacol Exp Ther. 2017 Jan;360(1):226-238. td> |
Molecular structures of BTK inhibitors GDC-0853, GNE-309, ibrutinib, and spebrutinib.J Pharmacol Exp Ther. 2017 Jan;360(1):226-238. td> |