| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
PI3K catalytic subunit p110delta (PI3Kdelta). Idelalisib D5 is a potent, highly selective, and ATP-competitive inhibitor of the class I PI3K p110delta isoform. It inhibits PI3Kdelta with an IC50 of 2.5 nM and exhibits 40- to 300-fold selectivity for p110delta over the other Class I PI3K isoforms (p110alpha/beta/gamma). By blocking PI3Kdelta, idelalisib disrupts B-cell receptor (BCR) and chemokine receptor signaling pathways, inhibiting B-cell proliferation, survival, and homing.
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| ln Vitro |
Idelalisib is a highly selective p110delta inhibitor with biochemical IC50 values of 2.5 nM (p110delta), 89 nM (p110gamma), 565 nM (p110beta), and 820 nM (p110alpha), respectively (40- to 300-fold selectivity for delta over alpha/beta/gamma). It inhibits downstream AKT phosphorylation (Ser473) in cells with an IC50 of 24 nM, and inhibits proliferation of primary CLL cells stimulated by CD40L + IL-4, BCR cross-linking, or chemokine stimulation with IC50s in the 0.5-5 uM range.
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| ln Vivo |
In a mouse model of human B-cell malignancies (e.g., REC-1 mantle cell lymphoma xenografts), oral Idelalisib (50-150 mg/kg BID) significantly inhibits tumor growth (TGI >80%), induces apoptosis, and prolongs survival. It also reduces lymphadenopathy (enlarged lymph nodes), inhibits BCR- and CXCL13-mediated CLL cell migration, reduces serum levels of inflammatory cytokines (MIP-1alpha, MIP-1beta, IL-6, TNFalpha), and reduces lymphocytosis.
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| Enzyme Assay |
Cell-free PI3K enzyme assays are performed using recombinant human PI3K isoforms (p110delta, p110alpha, p110beta, p110gamma). Each isoform (1-10 nM) is incubated with varying concentrations of Idelalisib D5 (0.01-1000 nM) in 50 mM HEPES (pH 7.5), 10 mM MgCl2, 1 mM DTT, and 10 uM ATP. The reaction is initiated by adding phosphatidylinositol (PI) substrate (100 uM) and incubated for 30 min at 30degC. PI3P production is measured using a competitive time-resolved fluorescence (TR-FRET) assay (e.g., PI3K HTRF kit). IC50 values for each isoform are calculated.
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| Cell Assay |
T-cell depleted primary human CLL cells are isolated from whole blood of CLL patients using magnetic bead separation. Cells are cultured in RPMI-1640 + 10% FBS and stimulated with anti-IgM (10 microg/mL) to cross-link BCR, or with CD40L + IL-4 (to mimic the lymph node microenvironment). Varying concentrations of Idelalisib D5 (0.1-1000 nM) are added for 1-2 h, followed by stimulation for 15-30 min. Cells are lysed and pAKT (Ser473, Thr308) is measured by Western blotting or AlphaLISA. The IC50 for inhibition of pAKT is calculated.
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| Animal Protocol |
C57BL/6 mice bearing EL4 murine lymphoma cells expressing human p110delta (transgenic) or immunocompromised mice (NSG) bearing primary human CLL xenografts are used. When tumors or lymphocytosis/splenomegaly develops, animals are randomized. Idelalisib (50-150 mg/kg) or vehicle is administered orally BID for 14-21 days. Tumor volumes (for xenografts), spleen weight (as a marker of disease burden), and circulating human CD19+CD5+ CLL cells (by flow cytometry) are measured. Idelalisib D5 is used as the internal standard for LC-MS/MS quantification in plasma and tumor samples.
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| ADME/Pharmacokinetics |
Idelalisib D5 is used as an internal standard (IS) for LC-MS/MS quantification. Idelalisib has an oral bioavailability of ~80-90%, a terminal half-life of ~8 h in humans, and is >94% protein bound. It is metabolized primarily by aldehyde oxidase (AO) (major pathway, ~70%) and CYP3A4 (minor pathway). The major circulating metabolite is GS-563117 (inactive), which is used as an IS in some assays.
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| Toxicity/Toxicokinetics |
The D5-labeled compound is for research only. Idelalisib carries a boxed warning for fatal and serious hepatotoxicity (severe ALT/AST elevations, fatal liver failure), severe diarrhea (including colitis), pneumonitis (interstitial lung disease, ILD), and intestinal perforation. Common AEs (≥30%): diarrhea (43%), nausea (30%), pyrexia (29%), fatigue (27%), and rash (25%). Hepatic monitoring (LFTs) is required every 2 weeks for the first 6 months of therapy.
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| References | |
| Additional Infomation |
Idelalisib (Zydelig) was FDA-approved in 2014 for relapsed CLL (in combination with rituximab), relapsed follicular lymphoma (FL), and relapsed SLL. It was the first approved PI3Kdelta inhibitor. The D5-labeled version is a research internal standard for LC-MS/MS bioanalysis, used in drug-drug interaction studies (especially with CYP3A4 and aldehyde oxidase), therapeutic drug monitoring (TDM), and bioequivalence trials. Clinical development has been impacted by significant hepatotoxicity concerns.
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| Molecular Formula |
C22H13D5FN7O
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|---|---|
| Molecular Weight |
420.45
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| Exact Mass |
420.187
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| CAS # |
1830330-31-8
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| Related CAS # |
Idelalisib;870281-82-6
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| PubChem CID |
91971682
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| Appearance |
White to off-white solid powder
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| LogP |
3.7
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
31
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| Complexity |
685
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| Defined Atom Stereocenter Count |
1
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| SMILES |
N1C(N[C@@H](CC)C2=NC3C(C(N2C2=C(C([2H])=C(C([2H])=C2[2H])[2H])[2H])=O)=C(C=CC=3)F)=C2N=CN=C2N=C1
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| InChi Key |
IFSDAJWBUCMOAH-LPJONKDZSA-N
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| InChi Code |
InChI=1S/C22H18FN7O/c1-2-15(28-20-18-19(25-11-24-18)26-12-27-20)21-29-16-10-6-9-14(23)17(16)22(31)30(21)13-7-4-3-5-8-13/h3-12,15H,2H2,1H3,(H2,24,25,26,27,28)/t15-/m0/s1/i3D,4D,5D,7D,8D
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| Chemical Name |
5-fluoro-3-(2,3,4,5,6-pentadeuteriophenyl)-2-[(1S)-1-(7H-purin-6-ylamino)propyl]quinazolin-4-one
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3784 mL | 11.8920 mL | 23.7840 mL | |
| 5 mM | 0.4757 mL | 2.3784 mL | 4.7568 mL | |
| 10 mM | 0.2378 mL | 1.1892 mL | 2.3784 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.
Products are for research use only; We do not sell to patients
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