| Size | Price | Stock | Qty |
|---|---|---|---|
| 1g |
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| 5g |
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| Other Sizes |
| Targets |
BTK; impurity of Ibrutinib
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|---|---|
| References |
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| Additional Infomation |
Activation of the B-cell antigen receptor (BCR) signaling pathway promotes the development and maintenance of B-cell malignancies and autoimmune diseases. Bruton's tyrosine kinase (Btk) is essential for BCR signaling, and dysfunctional mutations in Btk in humans and mice block B-cell maturation, a critical step in the maturation process requiring a functional BCR pathway. This article introduces a selective and irreversible Btk inhibitor, PCI-32765, which is currently undergoing clinical development in patients with B-cell non-Hodgkin lymphoma. We used this inhibitor to investigate the biological effects of Btk inhibition on mature B-cell function and the progression of B-cell-related diseases. PCI-32765 blocks BCR signaling in human peripheral blood B cells at concentrations that do not affect T-cell receptor signaling. In a mouse model of collagen-induced arthritis, oral administration of PCI-32765 reduced circulating autoantibody levels and completely inhibited disease progression. PCI-32765 also inhibited autoantibody production and the development of kidney disease in an MRL-Fas(lpr) lupus model. The occupancy of the Btk active site by PCI-32765 was monitored in vitro and in vivo using a Btk fluorescent affinity probe. Occupancy of the Btk active site was closely related to the blockade of the BCR signaling pathway and the efficacy of the treatment in vivo. In addition, PCI-32765 induced an objective clinical response in dogs with spontaneous B-cell non-Hodgkin lymphoma. These findings support Btk inhibition as a therapeutic strategy for treating human diseases associated with BCR pathway activation. [2]
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| Molecular Formula |
C17H13N5O
|
|---|---|
| Molecular Weight |
303.32
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| Exact Mass |
303.112
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| Elemental Analysis |
C, 68.17; H, 5.49; N, 19.08; O, 7.26
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| CAS # |
330786-24-8
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| PubChem CID |
22346757
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| Appearance |
Off-white to gray solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
577.4±50.0 °C at 760 mmHg
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| Flash Point |
303.0±30.1 °C
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| Vapour Pressure |
0.0±1.6 mmHg at 25°C
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| Index of Refraction |
1.734
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| LogP |
3.01
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
3
|
| Heavy Atom Count |
23
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| Complexity |
381
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C(C=C1)OC2=CC=C(C=C2)C3=C4C(=NC=NC4=NN3)N
|
| InChi Key |
YYVUOZULIDAKRN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H13N5O/c18-16-14-15(21-22-17(14)20-10-19-16)11-6-8-13(9-7-11)23-12-4-2-1-3-5-12/h1-10H,(H3,18,19,20,21,22)
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| Chemical Name |
3-(4-phenoxyphenyl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine
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| Synonyms |
330786-24-8; 3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine; 4-Amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidine; Ibrutinib deacryloylpiperidine; Ibrutinib N-2; MFCD20270360; 3-(4-phenoxyphenyl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine; 1H-Pyrazolo[3,4-d]pyrimidin-4-amine, 3-(4-phenoxyphenyl)-;
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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: 25 mg/mL (82.42 mM)
H2O: < 0.1 mg/mL |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (8.24 mM) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2968 mL | 16.4842 mL | 32.9685 mL | |
| 5 mM | 0.6594 mL | 3.2968 mL | 6.5937 mL | |
| 10 mM | 0.3297 mL | 1.6484 mL | 3.2968 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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