Item no. |
S2680-5 |
Manufacturer |
Selleckchem
|
CASRN |
936563-96-1 |
Amount |
5 mg |
Category |
|
Type |
Inhibitors |
Specific against |
other |
ECLASS 10.1 |
32160490 |
ECLASS 11.0 |
32160490 |
UNSPSC |
12000000 |
Alias |
936563-96-1' |
Similar products |
PCI-32765 |
Available |
|
Administration |
Administered via p.o. |
Animal Models |
MRL-Fas(lpr) lupus model and collagen-induced arthritis model. |
Cell lines |
Chronic lymphocytic leukemia (CLL) cells |
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 |
Clinical Trials |
PCI-32765 is currently in Phase II clinical trials in patients with, Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL). Combination of PCI-32765 and Rituximab is currently in Phase II clinical trials in patients with High-Risk Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL). |
Concentrations |
0.01-100 uM |
Description |
PCI-32765 (Ibrutinib) is a potent and highly selective Btk inhibitor with IC50 of 0.5 nM. |
Dosages |
<=50 mg/kg |
Formulation |
PCI-32765 is dissolved in DMSO. |
IC50 |
0.5 nM [1]
0.5 nM [1]
0.5 nM [1]
0.5 nM [1]
0.5 nM [1]
0.5 nM [1] |
In vitro |
PCI-32765 shows the potent and irreversible inhibitory effect and selectivity for Btk enzymatic activity. In BCR pathway-activated DOHH2 cell line, PCI-32765 inhibits autophosphorylation of Btk, phosphorylation of Btk's physiological substrate PLCgamma, and phosphorylation of further downstream kinase, ERK with IC50 of 11 nM, 29 nM and 13 nM, respectively. [1], PCI-32765 exhibits a significant dose-dependent and time-dependent induction of cytotoxicity in chronic lymphocytic leukemia (CLL) cells. In addition, PCI-32765 induces cell death depending on caspase pathway activation and antagonizes the ability of CLL cells to proliferate after TLR signaling. [2], A recent study shows that PCI-32765 inhibits BCR-activated primary B cell proliferation with IC50 of 8 nM and results in inhibition of TNFalpha, IL-1beta and IL-6 production in primary monocytes with IC50 of 2.6 nM, 0.5 nM and 3.9 nM, respectively. [3] |
In vivo |
In a collagen-induced arthritis model, PCI-32765 significantly reduces clinical arthritis scores reflecting paw swelling and joint inflammation by inhibiting B-cell activation. In a MRL-Fas(lpr) lupus model, PCI-32765 reduces renal disease and autoantibody production. [1], In an adoptive transfer TCL1 mouse model of CLL, PCI-32765 (25 mg/kg/day) causes a transient early lymphocytosis, and delays CLL disease progression. [4] |
Incubation Time |
48 hours |
Kinase Assay |
Kinase Assays, In vitro kinase IC50 values are measured using 33P filtration binding assay after 1 hour incubation of kinase, 33P-ATP, PCI-32765, and substrate [0.2 mg/mL poly(EY)(4:1]. Assays are performed at Reaction Biology. |
Method |
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 PCI-32765, 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 100M Z-VAD. |
Molecular Weight (MW) |
440, 5 |
Picture ChemicalStructure Description |
PCI-32765 (Ibrutinib) Chemical Structure |
Solubility (25C) |
DMSO 88 mg/mL, Water <1 mg/mL, Ethanol 2 mg/mL |
Storage |
2 years -20CPowder, 2 weeks4Cin DMSO, 2 months-80Cin DMSO |
Note: The presented information and documents (Manual, Product Datasheet, Safety Datasheet and Certificate of Analysis) correspond to our latest update and should serve for orientational purpose only. We do not guarantee the topicality. We would kindly ask you to make a request for specific requirements, if necessary.
All products are intended for research use only (RUO). Not for human, veterinary or therapeutic use.