product name Ibrutinib (PCI-32765)
Description: Ibrutinib, also known as PCI-32765, is a highly potent and selective, orally bioavailable Brutons tyrosine kinase (Btk) inhibitor with IC50 of 0.5 nM in cell-free assays, modestly potent to Bmx, CSK, FGR, BRK, HCK, less potent to EGFR, Yes, ErbB2, JAK3, etc. Ibrutinib binds to and inhibits BTK activity, preventing B-cell activation and B-cell-mediated signaling and inhibiting the growth of malignant B cells that overexpress BTK. Ibrutinib was approved by the US FDA on November 13, 2013 for the treatment of mantle cell lymphoma.
References: Proc Natl Acad Sci U S A. 2010;107(29):13075-80; Blood. 2011;117(23):6287-96; Blood. 2012;119(5):1182-9.
440.5
Formula
C25H24N6O2
CAS No.
936563-96-1
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 88 mg/mL (199.8 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
2% DMSO+Castor oil: 10 mg/mL
Synonyms
PCI-32765
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19401342
| In Vitro |
In vitro activity: Ibrutinib shows the potent and irreversible inhibitory effect and selectivity for Btk enzymatic activity. In BCR pathway-activated DOHH2 cell line, Ibrutinib inhibits autophosphorylation of Btk, phosphorylation of Btks physiological substrate PLCγ, and phosphorylation of further downstream kinase, ERK with IC50 of 11 nM, 29 nM and 13 nM, respectively. Ibrutinib exhibits a significant dose-dependent and time-dependent induction of cytotoxicity in chronic lymphocytic leukemia (CLL) cells. In addition, Ibrutinib induces cell death depending on caspase pathway activation and antagonizes the ability of CLL cells to proliferate after TLR signaling. A recent study shows that Ibrutinib inhibits BCR-activated primary B cell proliferation with IC50 of 8 nM and results in inhibition of TNFα, IL-1β and IL-6 production in primary monocytes with IC50 of 2.6 nM, 0.5 nM and 3.9 nM, respectively. Kinase Assay: In vitro kinase IC50 values are measured using 33P filtration binding assay after 1 hour incubation of kinase, 33P-ATP, Ibrutinib, and substrate [0.2 mg/mL poly(EY)(4:1]. Assays are performed at Reaction Biology. Cell Assay: MTT (3[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assays are performed to determine cytotoxicity. Briefly, cells (CLL B cells or healthy volunteer T cells or NK cells) are incubated for 48 hours with different concentrations of Ibrutinib, or vehicle control. MTT reagent is then added, and plates are incubated for an additional 20 hours before washing with protamine sulfate in phosphate-buffered saline. Dimethyl sulfoxide is added, and absorbance is measured by spectrophotometry at 540 nm in a Labsystems plate reader. Cell viability is also measured at various time points with the use of annexin/PI flow cytometry. Data are analyzed with Expo-ADC32 software package. Results are expressed as the percentage of total positive cells over untreated control. Experiments examining caspase-dependent apoptosis includes the addition of 100μM Z-VAD. |
|---|---|
| In Vivo | MRL-Fas(lpr) lupus model and collagen-induced arthritis model. |
| Animal model | Male 5-week-old BALB-nu/nu with HPAC cells |
| Formulation & Dosage | Dissolved in DMSO; 50 mg/kg; Oral gavage |
| References | Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):13075-80; Blood. 2011 Jun 9;117(23):6287-96; Blood. 2012 Feb 2;119(5):1182-9. |
Related Posts
product name Ibrutinib (PCI-32765)
Description: Ibrutinib, also known as PCI-32765, is a highly potent and selective, orally bioavailable Brutons tyrosine kinase (Btk) inhibitor with IC50 of 0.5 nM in cell-free assays, modestly potent to Bmx, CSK, FGR, BRK, HCK, less potent to EGFR, Yes, ErbB2, JAK3, etc. Ibrutinib binds to and inhibits BTK activity, preventing B-cell activation and B-cell-mediated signaling and inhibiting the growth of malignant B cells that overexpress BTK. Ibrutinib was approved by the US FDA on November 13, 2013 for the treatment of mantle cell lymphoma.
References: Proc Natl Acad Sci U S A. 2010;107(29):13075-80; Blood. 2011;117(23):6287-96; Blood. 2012;119(5):1182-9.
440.5
Formula
C25H24N6O2
CAS No.
936563-96-1
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 88 mg/mL (199.8 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
2% DMSO+Castor oil: 10 mg/mL
Synonyms
PCI-32765
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19401342
| In Vitro |
In vitro activity: Ibrutinib shows the potent and irreversible inhibitory effect and selectivity for Btk enzymatic activity. In BCR pathway-activated DOHH2 cell line, Ibrutinib inhibits autophosphorylation of Btk, phosphorylation of Btks physiological substrate PLCγ, and phosphorylation of further downstream kinase, ERK with IC50 of 11 nM, 29 nM and 13 nM, respectively. Ibrutinib exhibits a significant dose-dependent and time-dependent induction of cytotoxicity in chronic lymphocytic leukemia (CLL) cells. In addition, Ibrutinib induces cell death depending on caspase pathway activation and antagonizes the ability of CLL cells to proliferate after TLR signaling. A recent study shows that Ibrutinib inhibits BCR-activated primary B cell proliferation with IC50 of 8 nM and results in inhibition of TNFα, IL-1β and IL-6 production in primary monocytes with IC50 of 2.6 nM, 0.5 nM and 3.9 nM, respectively. Kinase Assay: In vitro kinase IC50 values are measured using 33P filtration binding assay after 1 hour incubation of kinase, 33P-ATP, Ibrutinib, and substrate [0.2 mg/mL poly(EY)(4:1]. Assays are performed at Reaction Biology. Cell Assay: MTT (3[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assays are performed to determine cytotoxicity. Briefly, cells (CLL B cells or healthy volunteer T cells or NK cells) are incubated for 48 hours with different concentrations of Ibrutinib, or vehicle control. MTT reagent is then added, and plates are incubated for an additional 20 hours before washing with protamine sulfate in phosphate-buffered saline. Dimethyl sulfoxide is added, and absorbance is measured by spectrophotometry at 540 nm in a Labsystems plate reader. Cell viability is also measured at various time points with the use of annexin/PI flow cytometry. Data are analyzed with Expo-ADC32 software package. Results are expressed as the percentage of total positive cells over untreated control. Experiments examining caspase-dependent apoptosis includes the addition of 100μM Z-VAD. |
|---|---|
| In Vivo | MRL-Fas(lpr) lupus model and collagen-induced arthritis model. |
| Animal model | Male 5-week-old BALB-nu/nu with HPAC cells |
| Formulation & Dosage | Dissolved in DMSO; 50 mg/kg; Oral gavage |
| References | Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):13075-80; Blood. 2011 Jun 9;117(23):6287-96; Blood. 2012 Feb 2;119(5):1182-9. |