| Size | Price | Stock | Qty |
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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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| Other Sizes |
| Targets |
WT BTK (IC50 = 51.0 nM); C481S BTK (IC50 = 30.7 nM)
N-piperidine Ibrutinib HCl targets Bruton’s tyrosine kinase (BTK), a key enzyme in B-cell receptor signaling. BTK plays a critical role in the proliferation, survival, and activation of B cells. The compound binds to the BTK active site and inhibits its kinase activity. It is a reversible inhibitor. The compound is also used as a ligand for PROTACs, where it recruits BTK to E3 ubiquitin ligases for degradation. It is effective against both wild-type BTK and the C481S mutant, which is associated with resistance to irreversible BTK inhibitors like Ibrutinib. |
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| ln Vitro |
N-piperidine ibrutinib hydrochloride is a BTK ligand that can be utilized in the production of several PROTACs. Effective PROTAC BTK degraders are SJF638, SJF678, and SJF608, with DC50 values of 374, 162, and 8.3 nM, respectively [2].
In vitro, N-piperidine Ibrutinib HCl is a potent BTK inhibitor. It inhibits wild-type BTK with an IC50 of 51.0 nM and the C481S BTK mutant with an IC50 of 30.7 nM. In cell-based assays, the compound inhibits BTK phosphorylation and downstream signaling. When used as a PROTAC ligand, N-piperidine Ibrutinib HCl is incorporated into PROTAC molecules such as SJF620, SJF638, SJF678, and SJF608, which degrade BTK with DC50 values of 7.9 nM, 374 nM, 162 nM, and 8.3 nM, respectively. These in vitro activities confirm its utility as a BTK inhibitor and as a ligand for targeted protein degradation. |
| ln Vivo |
In vivo activity of N-piperidine Ibrutinib HCl is evaluated in the context of PROTACs synthesized with this compound. PROTACs such as SJF620 have demonstrated efficacy in degrading BTK in vivo and inhibiting tumor growth in animal models of B-cell malignancies. The compound’s ability to target both wild-type and C481S BTK makes it valuable for overcoming resistance to irreversible BTK inhibitors. These studies support the potential of N-piperidine Ibrutinib HCl as a key component of next-generation BTK-targeted therapies.
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| Enzyme Assay |
In vitro enzyme assays for N-piperidine Ibrutinib HCl involve measuring its inhibition of BTK kinase activity. These assays use recombinant BTK (wild-type or C481S mutant) and a peptide substrate. The enzyme is incubated with ATP and the substrate in the presence of varying concentrations of the compound. Phosphorylation of the substrate is measured, and the IC50 is calculated. These assays confirm the compound’s potency as a BTK inhibitor and its activity against the C481S mutant.
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| Cell Assay |
In vitro cellular assays for N-piperidine Ibrutinib HCl are conducted in B-cell lines such as Ramos, Raji, or primary B cells. Cells are treated with the compound at various concentrations, and BTK phosphorylation is measured by Western blot or phospho-specific ELISA. Cell proliferation is measured using MTT or CellTiter-Glo assays. When used in PROTACs, BTK degradation is measured by Western blot, and the DC50 is calculated. These assays characterize the compound’s activity as a BTK inhibitor and its utility for PROTAC-based degradation.
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| Animal Protocol |
In vivo animal experiments with N-piperidine Ibrutinib HCl are conducted using PROTACs synthesized with this compound. Mouse xenograft models of B-cell malignancies (e.g., Ramos, Raji) are used. The PROTAC is administered intravenously or orally, and tumor growth is measured. BTK levels in tumors are measured by Western blot to confirm degradation. Pharmacodynamic studies are performed to assess the relationship between BTK degradation and antitumor efficacy.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for N-piperidine Ibrutinib HCl are relevant in the context of PROTACs synthesized with this compound. The linker itself is not administered as a free drug but as part of a PROTAC. The pharmacokinetics of the PROTAC are influenced by the properties of the ligands and the linker. The compound’s ability to target the C481S mutant makes it a promising component for overcoming resistance. Detailed PK studies are conducted for each PROTAC individually.
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| Toxicity/Toxicokinetics |
Toxicological data for N-piperidine Ibrutinib HCl are evaluated as part of the safety assessment of PROTACs incorporating this compound. The compound itself is not typically tested alone, but the toxicity of the PROTAC is assessed in preclinical studies. The safety profile depends on the specific ligands and the target protein. Standard toxicology studies are conducted to assess the safety of PROTACs containing this BTK ligand.
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| References |
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| Additional Infomation |
N-piperidine Ibrutinib HCl is a potent BTK inhibitor and a BTK ligand used in the synthesis of PROTACs. It is a reversible Ibrutinib derivative that inhibits both wild-type BTK (IC50 = 51.0 nM) and the C481S mutant (IC50 = 30.7 nM). The compound is used as a BTK ligand in the synthesis of PROTACs such as SJF620, which degrades BTK with a DC50 of 7.9 nM. This dual functionality—inhibition and degradation—makes it a valuable tool for BTK-targeted therapy research.
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| Molecular Formula |
C22H23CLN6O
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|---|---|
| Molecular Weight |
422.910622835159
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| Exact Mass |
422.16
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| Elemental Analysis |
C, 62.48; H, 5.48; Cl, 8.38; N, 19.87; O, 3.78
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| CAS # |
2231747-18-3
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| Related CAS # |
2231747-18-3
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| PubChem CID |
139465991
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| Appearance |
White to off-white solid
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
30
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| Complexity |
515
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CNCCC1N2C3=NC=NC(=C3C(=N2)C4=CC=C(C=C4)OC5=CC=CC=C5)N.Cl
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| InChi Key |
ORBFZIXZKIUECG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H22N6O.ClH/c23-21-19-20(15-6-8-18(9-7-15)29-17-4-2-1-3-5-17)27-28(22(19)26-14-25-21)16-10-12-24-13-11-16;/h1-9,14,16,24H,10-13H2,(H2,23,25,26);1H
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| Chemical Name |
3-(4-phenoxyphenyl)-1-piperidin-4-ylpyrazolo[3,4-d]pyrimidin-4-amine;hydrochloride
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| Synonyms |
Npiperidine; Ibrutinib HCl; N piperidine; Ibrutinib 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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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) |
Water: ~85 mg/mL (~201 mM)
DMSO: ~11 mg/mL (~26.0 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.91 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
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. Solubility in Formulation 2: 2.5 mg/mL (5.91 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.91 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3646 mL | 11.8228 mL | 23.6457 mL | |
| 5 mM | 0.4729 mL | 2.3646 mL | 4.7291 mL | |
| 10 mM | 0.2365 mL | 1.1823 mL | 2.3646 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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