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| 10mg |
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| 250mg |
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| 500mg |
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| 1g |
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Purity: ≥98%
Ibrutinib (formerly PCI32765; trade name Imbruvica), an approved anticancer drug, is a covalent/irreversible and orally bioavailable Brutons tyrosine kinase (Btk) inhibitor with potential anti-cancer activity. It inhibits BTK with an IC50 of 0.5 nM in cell-free assays, and exhibits modest potency against other kinases such as Bmx, CSK, FGR, BRK, HCK, less potent to EGFR, Yes, ErbB2, JAK3, etc. on November 13th 2013, Ibrutinib was approved by the US FDA for the treatment of mantle cell lymphoma.
| Targets |
BTK (IC50=0.5 nM)
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| ln Vitro |
B-cell activity and signaling are specifically inhibited by imatinib (PCI-32765). It prevents Btk (IC50=11 nM) from autophosphorylating, Btk's physiological substrate PLCγ (IC50=29 nM) from being phosphorylated, and ERK (IC50=13 nM), a further downstream kinase, from being phosphorylated[1]. BCR-activated primary B cell growth is inhibited by imatinib (PCI-32765) (IC50=8 nM). Ibrutinib (PCI-32765) suppresses the production of TNFα, IL-1β, and IL-6 in primary monocytes after FcγR stimulation (IC50=2.6, 0.5, and 3.9 nM, respectively)[3]. Cysteine481, or C481 of BTK, is bound by imatinib, with an optimal IC50 of 0.5 nM. The hydroxyl group of serine is incompatible with imatinib, and the C481S mutation raises the IC50 against BTK-C481S phosphorylation from 2.2 nM to 1 μM[4].
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| ln Vivo |
In mice with collagen-induced arthritis, ibrutinib (PCI-32765) (3.125–50 mg/kg, po) totally suppresses the disease and lowers the amount of circulating autoantibodies. In the MRL-Fas(lpr) lupus model, imatinib (PCI-32765) prevents the formation of autoantibodies and the progression of kidney disease. In MRL-Fas(lpr) mice, ibrutinib (PCI-32765) (3.125–50 mg/kg, po) ameliorates renal disease and autoantibody production[1]. When compared to T cells, Ibrutinib (PCI-32765) (0.1 μM) selectively cytotoxically affects B cells, but it modifies the production of cytokines by activated T cells. It also inhibits the proliferation of CLL cells when activated. In a therapeutic CIA model, ibrutinib (PCI-32765) with an ED50 of 2.6 mg/kg/day potently and dose-dependently reverses arthritic inflammation. Clinical arthritis is also prevented in CAIA models by ibrutinib (PCI-32765)[3].
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| Enzyme Assay |
After incubating with kinase, 33P-ATP, Ibrutinib, and substrate [0.2 mg/mL poly (EY) (4:1)] for 1 hour, the in vitro kinase IC50 values were measured using a 33P filtration binding assay.
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| Cell Assay |
B and T Cells. CD20+ B and CD3+ T cells were purified by negative selection (RosetteSep, >90% purity) from buffy coat PBMCs and viably frozen in 10% DMSO. Cells were thawed at 37 °C and maintained in growth media (RPMI media containing 10% FCS). B cells were stimulated with goat antihuman IgM F(ab′)2 (10 μg/mL; Invitrogen) and T cells were stimulated with anti-CD3/CD28 coated beads (Dynabeads) at a 1:1 bead/cell ratio. Cells were stained with PE-CD69 (BD Biosciences) and analyzed by flow cytometry, gating on viable lymphocytes. PCI-32765 at concentrations lower than 10 μM did not decrease B- or T-cell viability during the course of the experiment, although PCI-32765 did block the modest survival benefit of anti-IgM stimulation in B cells. For washout experiments, cells were rinsed three times in 10 volumes of growth media, a protocol that was confirmed to completely wash away inhibition of BCR signaling by PCI-29732, a reversible Btk inhibitor.[1]
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| Animal Protocol |
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| References |
[1]. Honigberg LA, et al. The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy. Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):13075-80.
[2]. Herman SE, et al. Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765. Blood. 2011 Jun 9;117(23):6287-96. [3]. Chang BY, et al. The Bruton tyrosine kinase inhibitor PCI-32765 ameliorates autoimmune arthritis by inhibition of multiple effector cells. Arthritis Res Ther. 2011 Jul 13;13(4):R115. [4]. Sun Y, et al. PROTAC-induced BTK degradation as a novel therapy for mutated BTK C481S induced ibrutinib-resistant B-cell malignancies. Cell Res. 2018 Jul;28(7):779-781 |
| Molecular Formula |
C25H24N6O2
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|---|---|
| Molecular Weight |
440.5
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| Exact Mass |
440.20
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| Elemental Analysis |
C, 68.17; H, 5.49; N, 19.08; O, 7.26
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| CAS # |
936563-96-1
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| Related CAS # |
Ibrutinib Racemate;936563-87-0;Ibrutinib-d5;1553977-17-5
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| Appearance |
White to off-white solid powder
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| LogP |
3.6
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| tPSA |
99.2Ų
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| SMILES |
C=CC(N1C[C@H](N2N=C(C3=CC=C(OC4=CC=CC=C4)C=C3)C5=C(N)N=CN=C52)CCC1)=O
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| InChi Key |
XYFPWWZEPKGCCK-GOSISDBHSA-N
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| InChi Code |
InChI=1S/C25H24N6O2/c1-2-21(32)30-14-6-7-18(15-30)31-25-22(24(26)27-16-28-25)23(29-31)17-10-12-20(13-11-17)33-19-8-4-3-5-9-19/h2-5,8-13,16,18H,1,6-7,14-15H2,(H2,26,27,28)/t18-/m1/s1
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| Chemical Name |
(R)-1-(3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one.
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| Synonyms |
PCI-32765; PCI-32765, Ibrutinib, PCI 32765, trade name: Imbruvica
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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) |
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| Solubility (In Vivo) |
Formulation 1: ~10 mg/mL (23 mM) in 2% DMSO+Castor oil, clear solution
Formulation 2: ≥ 2.5 mg/mL (5.7 mM) in 5% DMSO + 95% (20% SBE-β-CD in saline), clear solution Formulation 3: ≥ 2.5 mg/mL (5.7 mM) in 10% DMSO + 90% (20% SBE-β-CD in saline), suspension solution Formulation 4: ≥ 2.5 mg/mL (5.7 mM) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline, clear solution Formulation 5: ≥ 2.5 mg/mL (5.7 mM) in 10% DMSO + 90% Corn oil, clear solution Formulation 6: ~3.4 mg/mL (7.6 mM) in 0.5% MC+ 0.5% Tween-80, suspension solution (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2701 mL | 11.3507 mL | 22.7015 mL | |
| 5 mM | 0.4540 mL | 2.2701 mL | 4.5403 mL | |
| 10 mM | 0.2270 mL | 1.1351 mL | 2.2701 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT04771507 | Recruiting | Drug: Ibrutinib | Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma |
Jeanette Lundin | February 23, 2018 | Phase 1 Phase 2 |
| NCT05348096 | Unknown | Drug:Low-dose ibrutinib | Chronic Graft-versus -host-disease |
Hospital Universitario Dr. Jose E. Gonzalez |
April 1, 2022 | Phase 2 |
| NCT04908228 | Recruiting | Drug:Ibrutinib and obinutuzumab |
Chronic Lymphocytic Leukemia | Paolo Ghia | December 13, 2021 | Phase 2 |
| NCT03207555 | Active,not recruiting | Drug: Ibrutinib | Chronic Lymphocytic Leukemia Ibrutinib Resistance |
M.D. Anderson Cancer Center |
May 23, 2018 | Phase 2 |
| NCT03731234 | Recruiting | Drug: Ibrutinib | DLBCL | Fondazione Italiana Linfomi - ETS |
July 2, 2019 | Phase 2 |
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