Idelalisib

SKU: orb1307216

Description

Idelalisib is a potent and selective small molecule inhibitor of the PI3K p110δ isoform, demonstrating 40- to 300-fold selectivity over other PI3K class I isoforms. It is widely used in biochemical and cellular research to investigate B-cell malignancies and immune cell signaling, with applications in both in vitro and in vivo models of hematologic cancers.

Research Area

Cell Biology, Signal Transduction

Key Properties

• CAS Number: 870281-82-6
• MW: 415.42
• Purity: 99.94%
• Formula: C₂₂H₁₈FN₇O
• SMILES: [C@H](NC1=C2C(N=CN2)=NC=N1)(CC)C=3N(C(=O)C=4C(N3)=CC=CC4F)C5=CC=CC=C5
• Target: Autophagy,PI3K
• Solubility: Ethanol:22 mg/mL (52.96 mM);H2O:Insoluble;10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (4.81 mM);DMSO:250 mg/mL (601.8 mM)

Bioactivity

• Target IC50:
  DNA-PK:6729 nM|p110δ:2.5 nM (cell free)|p110α:820 nM|p110γ:89 nM (cell free)|p110β:565 nM (cell free)|hVps34:978 nM
• In Vivo:
  A single intravenous dose of 40 mg/kg of Idelalisib, given 15 min before ischemia in wild-type mice (pre-treatment), significantly reduced infarction after 72 h. However, lower doses (20, 10 and 1 mg/kg) did not achieve significant protection. Importantly, even when given 3 h after the onset of reperfusion (post-treatment), a dose of 40 mg Idelalisib per kg body weight was still effective in reducing the infarct volume by an average of 44% compared with the vehicle-treated control group .
• In Vitro:
  Idelalisib is an oral p110δ inhibitor currently under clinical evaluation in patients with B-cell malignancies. Idelalisib was 40- to 300-fold more selective for p110δ relative to other PI3K class I enzymes (IC50 p110δ = 2.5nM; p110α, p110β, and p110γ IC50 were 820, 565, and 89nM, respectively). Greater selectivity (400- to 4000-fold) was seen against related kinases C2β, hVPS34, DNA-PK, and mTOR, whereas no activity was observed against a panel of 402 diverse kinases at 10μM . Idelalisib promoted apoptosis in primary CLL cells ex vivo in a dose- and time-dependent fashion that was independent of common prognostic markers. Idelalisib-mediated cytotoxicity was caspase-dependent and was not diminished by coculture on stromal cells . CAL-101 inhibits CLL cell chemotaxis toward CXCL12 and CXCL13 and migration beneath stromal cells (pseudoemperipolesis). Idelalisib also down-regulates secretion of chemokines in stromal cocultures and after BCR triggering. Idelalisib reduces survival signals derived from the BCR or from nurse-like cells, and inhibits BCR- and chemokine-receptor-induced AKT and MAP kinase (ERK) activation .
• Cell Research:
  MTT assays were performed to determine cytotoxicity. Briefly, 1 × 10^5 cells (CLL B cells or healthy volunteer T cells or NK cells) were incubated for 48 hours with different concentrations of CAL-101, 25μM LY294002, or vehicle control. MTT reagent was then added, and plates were incubated for an additional 20 hours before washing with protamine sulfate in phosphate-buffered saline. Dimethyl sulfoxide was added, and absorbance was measured by spectrophotometry at 540 nm in a Labsystems plate reader. Cell viability was also measured at various time points with the use of annexin/PI flow cytometry. Data were analyzed with Expo-ADC32 software package. At least 10 000 cells were counted for each sample. Results were expressed as the percentage of total positive cells over untreated control. Experiments examining caspase-dependent apoptosis included the addition of 100μM Z-VAD. Experiments examining survival signals included the addition of 1 μg/mL CD40L, 800 U/mL IL-4, 50 ng/mL BAFF, 20 ng/mL TNF-α, or coculturing on fibronectin or stromal (HS-5 cell line) coated plates. Stromal coculture was done by plating a 75-cm2 flask (80%-100% confluent) per 6-well plate 24 hours before the addition of CLL cells .
• Animal Research:
  For Idelalisib (CAL-101) treatment, wild-type C57BL/6 mice were administered either 40 mg kg 1 CAL-101 or vehicle DMSO, by 25 ml infusion into the femoral vein, 15 min before I/R (pre-treatment), or 3 and 6 h after initiation of reperfusion (post-treatment). Controls and animals treated with CAL-101 underwent cerebral blood flow (CBF) measurements using a laser Doppler perfusion monitor. The CBF measurements obtained immediately before and after MCAO and again at 3 h after reperfusion showed a B90–95% reduction in the blood flow to the MCAO infarct region, which did not differ between groups .

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

PI3K, Phosphoinositide 3-kinase, Inhibitor, GS 1101, GS1101, GS-1101, Idelalisib, inhibit, p110δ, p110γ, Autophagy, CAL 101, CAL101, CAL-101

Compound Identifiers

PubChem CID

11625818