| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
Purity: ≥98%
PF-06250112 is a novel, potent, highly selective, orally bioavailable BTK inhibitor with an IC50 of 0.5 nM, shows inhibitory effect toward BMX nonreceptor tyrosine kinase and TEC with IC50s of 0.9 nM and 1.2 nM, respectively. PF-06250112 inhibits both BCR-mediated signaling and proliferation, as well as FcR-mediated activation. To assess the therapeutic impact of BTK inhibition, aged NZBxW_F1 mice were treated with PF-06250112 and demonstrate that PF-06250112 significantly limits the spontaneous accumulation of splenic germinal center B cells and plasma cells. Correspondingly, anti-dsDNA and autoantibody levels were reduced in a dose-dependent manner. Moreover, administration of PF-06250112 prevented the development of proteinuria and improved glomerular pathology scores in all treatment groups. Strikingly, this therapeutic effect could occur with only a modest reduction observed in anti-dsDNA titers, implying a critical role for BTK signaling in disease pathogenesis beyond inhibition of autoantibody production. PF-06250112 prevents proteinuria in an FcR-dependent, Ab-mediated model of glomerulonephritis. Importantly, these results highlight that BTK inhibition potently limits the development of glomerulonephritis by impacting both cell- and effector molecule-mediated pathways. These data provide support for evaluating the efficacy of BTK inhibition in systemic lupus erythematosus patients.
| ln Vitro |
PF-06250112 prevented the development of proteinuria in both a spontaneous model of SLE and an effector phase–restricted model mediated by administration of anti-GBM Abs. [1]
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|---|---|
| ln Vivo |
In NZBxW_F1 mice, treatment with PF-06250112 significantly reduced spontaneous germinal center and plasma cell formation. [1]
Treatment with PF-06250112 prevented the development of glomerulonephritis in the Ab-driven, anti-GBM–induced nephritis model.[1] |
| Cell Assay |
Isolated B cells were resuspended at 50 × 106/ml in PBS, and 5 × 106 cells were treated with different concentrations of PF-06250112 or DMSO as a vehicle control for 1 h at 37°C. Cells were then stimulated with 15 μg/ml anti-human IgM for 5 min at 37°C, lysed in cell lysis buffer containing protease and phosphatase inhibitors . [1]
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| Animal Protocol |
NZBxW_F1 mice were treated daily with PF-06250112 or vehicle by oral gavage. For anti-glomerlular basement membrane-induced nephritis studies, mice were treated by oral gavage with PF-06250112 or vehicle 2 h before injection of mouse anti-rabbit IgG mAb and treatment was continued daily thereafter.[1]
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| References |
| Molecular Weight |
438.430010795593
|
|---|---|
| Exact Mass |
438.161
|
| CAS # |
1609465-89-5
|
| Related CAS # |
(Rac)-PF-06250112;1609465-88-4
|
| PubChem CID |
90118673
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| Appearance |
Typically exists as solid at room temperature
|
| LogP |
3.5
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
32
|
| Complexity |
712
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
C1C[C@@H](CN(C1)C#N)N2C(=C(C(=N2)C3=CC=C(C=C3)OC4=C(C=C(C=C4)F)F)C(=O)N)N
|
| InChi Key |
SQFDBQCBXUWICP-HNNXBMFYSA-N
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| InChi Code |
InChI=1S/C22H20F2N6O2/c23-14-5-8-18(17(24)10-14)32-16-6-3-13(4-7-16)20-19(22(27)31)21(26)30(28-20)15-2-1-9-29(11-15)12-25/h3-8,10,15H,1-2,9,11,26H2,(H2,27,31)/t15-/m0/s1
|
| Chemical Name |
1‐(1‐Cyanopiperidine‐3α‐yl)‐3‐[4‐(2,4‐difluorophenoxy)phenyl]‐5‐amino‐1H‐pyrazole‐4‐carboxamide
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| Synonyms |
PF-06250112; PF 06250112; PF06250112.
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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 | 2.2809 mL | 11.4043 mL | 22.8087 mL | |
| 5 mM | 0.4562 mL | 2.2809 mL | 4.5617 mL | |
| 10 mM | 0.2281 mL | 1.1404 mL | 2.2809 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.
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