| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Leniolisib-d5 targets the same molecular target as Leniolisib: phosphoinositide 3-kinase delta (PI3Kdelta, PIK3CD). PI3Kdelta is a class I PI3K isoform primarily expressed in leukocytes (immune cells). It plays a critical role in B-cell receptor (BCR) signaling, T-cell activation, mast cell function, and other immune cell processes. PI3Kdelta is an important target for the treatment of primary immunodeficiencies (such as activated PI3K delta syndrome, APDS) and autoimmune diseases, as well as B-cell malignancies. The deuterated version has the same target selectivity. However, Leniolisib-d5 is not used for pharmacological studies; it is used as an analytical standard.
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| ln Vitro |
Stable heavy isotopes of hydrogen, carbon, and other elements have been incorporated into drug molecules, largely as tracers for quantitation during the drug development process. Studies involving the human use of drugs with labeled deuterium suggest that these compounds may offer some advantages when compared with their nondeuterated counterparts. Deuteration has gained attention because of its potential to affect the pharmacokinetic and metabolic profiles of drugs. Deutetrabenazine is the first deuterated drug to receive Food and Drug Administration approval. This deuterated form of the drug tetrabenazine is indicated for the treatment of chorea associated with Huntington's disease as well as tardive dyskinesia. Ongoing clinical trials suggest that a number of other deuterated compounds are being evaluated for the treatment of human diseases and not merely as research tools. [1]
Leniolisib-d5 has no intrinsic biological activity distinct from Leniolisib, but as an analytical standard it is not used in cell-based assays for biological activity. Leniolisib (the parent compound) is a potent and selective PI3Kdelta inhibitor with IC50 in the low nanomolar range (e.g., IC50 ~ 2-10 nM for PI3Kdelta, with selectivity over other PI3K isoforms alpha, beta, gamma typically >100-1000 fold). Leniolisib-d5 would be expected to exhibit the same selectivity and potency, but it is not used for that purpose. The deuterated version is used to normalize LC-MS/MS data and is generally not tested in vitro for activity. No specific in vitro activity data for the d5 version are reported. |
| ln Vivo |
Oral leniolisib lead to a dose-dependent reduction in PI3K/AKT pathway activity and resolve the immune dysregulation with normalization of circulating transitional and na?ve B cells and reduction in PD-1+CD4+ and senescent CD57+CD8+ T cells. After 12 weeks of treatment, all patients show amelioration of lymphoproliferation with lymph node sizes and spleen volumes reduced by 39% (mean, range 26-57%) and 40% (mean, range: 13-65%), respectively[2].
Leniolisib-d5 has no in vivo activity distinct from Leniolisib. As an analytical standard, it is not administered to animals for pharmacodynamic evaluation. Leniolisib (non-deuterated) has shown in vivo efficacy in mouse models of B-cell malignancies and in patients with activated PI3K delta syndrome (APDS). Leniolisib reduces PI3Kdelta signaling, decreases AKT phosphorylation, and restores immune cell homeostasis. Leniolisib-d5 is used in pharmacokinetic studies as an internal standard to quantify Leniolisib concentrations in plasma and tissues following administration of Leniolisib. It is not used as a therapeutic agent in animals and should not be administered to animals at high doses due to the potential for toxicity; only trace amounts are used for analytical purposes. |
| Enzyme Assay |
Leniolisib-d5 is a stable isotope-labeled compound and is not evaluated in enzyme/receptor binding assays for its own affinity. It is used as an analytical internal standard. The binding affinity of Leniolisib (parent compound) to PI3Kdelta is measured by standard in vitro kinase assays using purified recombinant human PI3Kdelta (and PI3Kalpha, beta, gamma for selectivity determination). Leniolisib is incubated with the kinase, phosphatidylinositol-4,5-bisphosphate (PIP2) substrate, and ATP. The amount of PIP3 produced is quantified by fluorescence polarization (FP) or HTRF, or by ADP-Glo™ kinase assay. IC50 for PI3Kdelta is in the low nanomolar range. The selectivity over other PI3K isoforms is >100-1000 fold. Leniolisib-d5 is assumed to have the same binding affinity as Leniolisib, but this is not experimentally determined for the labeled version.
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| Cell Assay |
Leniolisib-d5 is not used in cellular assays for activity. Cellular assays for Leniolisib (parent compound) are performed using B-cell lines (e.g., Ramos, Raji) or primary human B cells. Cells are seeded in 96-well plates and treated with Leniolisib (0.01-1000 nM) for 1-2 h. Cells are then stimulated with anti-IgM (for BCR activation). PI3Kdelta activity is assessed by measuring AKT phosphorylation at Ser473 (by Western blot or phospho-flow cytometry). IC50 values for inhibition of pAKT are typically in the low nanomolar range. Cell proliferation is measured by [3H]thymidine incorporation or CellTiter-Glo after 48-72 h of stimulation. Leniolisib-d5 is not used in these assays due to the potential for isotope effects (which are minimal but not zero) and the high cost of the labeled compound.
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| Animal Protocol |
Leniolisib-d5 is not used in animal experiments for pharmacodynamic evaluation. For pharmacokinetic studies, Leniolisib (non-deuterated) is administered to mice or rats (oral or intravenous, typically 1-30 mg/kg). Blood samples are collected at various time points (0, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24 h) via tail vein or cardiac puncture. Plasma is separated by centrifugation. A known amount of Leniolisib-d5 is added to each plasma sample as an internal standard. Leniolisib and the deuterated internal standard are extracted by protein precipitation or solid-phase extraction, and analyzed by LC-MS/MS using multiple reaction monitoring (MRM). The concentration of Leniolisib in each sample is calculated by comparing the peak area ratio of Leniolisib to Leniolisib-d5 to a standard curve. This method is used to calculate PK parameters: Cmax, Tmax, AUC, t1/2, clearance, volume of distribution, and oral bioavailability.
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| ADME/Pharmacokinetics |
Leniolisib-d5 (Molecular weight approximately 407.5 for the base plus 5 deuterium atoms, exact formula: C21H21D₅N₆O2, or similar depending on the labeling positions) is a solid powder. For storage, the compound should be kept at -20degC sealed, away from moisture and light. For analytical use, stock solutions are prepared in methanol or acetonitrile (typically 100 microg/mL or 1 mg/mL) and stored at -20degC or -80degC. The compound is stable under these conditions for extended periods (years). For LC-MS/MS analysis, a calibration curve is prepared by spiking blank plasma (or matrix) with known concentrations of Leniolisib and a fixed concentration of Leniolisib-d5 (e.g., 10-100 ng/mL). The linear range and LLOQ (lower limit of quantification) are determined. No PK data are generated for Leniolisib-d5 itself, as it is not administered in vivo; it is used only as an internal standard.
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| Toxicity/Toxicokinetics |
No toxicity data are reported for Leniolisib-d5, as it is not used in vivo for therapeutic purposes and is only used as an analytical standard at trace concentrations. Leniolisib (non-deuterated) has been evaluated in clinical trials and has a manageable safety profile. The most common adverse events associated with Leniolisib include diarrhea, rash, and fatigue. No specific toxicity data for the deuterated version are reported. Leniolisib-d5 is for research use only and is not intended for human or animal administration except as an analytical internal standard. Standard laboratory safety precautions for handling synthetic chemicals should be followed.
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| References |
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| Additional Infomation |
Leniolisib-d5 (CDZ173-d5) is a stable isotope-labeled internal standard for the quantification of Leniolisib (CDZ173) in biological samples by LC-MS/MS. Leniolisib is a potent and selective inhibitor of phosphoinositide 3-kinase delta (PI3Kdelta) developed by Novartis. Leniolisib was approved by the FDA in March 2023 for the treatment of activated PI3K delta syndrome (APDS), a rare primary immunodeficiency, making it the first targeted therapy approved for APDS. APDS is caused by gain-of-function mutations in the PIK3CD (PI3Kdelta) gene, leading to hyperactive PI3Kdelta signaling, immunodeficiency, lymphoproliferation, and autoimmunity. Leniolisib is available as a tablet (Joenja) for oral use. Leniolisib-d5 is for research use only and is not for human consumption. The deuterated version typically has 5 deuterium atoms (d5) replacing hydrogen atoms at metabolically stable positions, providing a mass shift of +5 Da for LC-MS/MS analysis. The deuterated compound is used in pharmacokinetic studies (preclinical and clinical) to accurately measure Leniolisib concentrations. It is not intended for therapeutic use.
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| Molecular Formula |
C21H20D5F3N6O2
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|---|---|
| Molecular Weight |
455.49
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| Appearance |
Solid powder
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| Synonyms |
CDZ173-d5
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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) |
DMSO : 100 mg/mL (219.54 mM; with sonication)
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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 | 2.1954 mL | 10.9772 mL | 21.9544 mL | |
| 5 mM | 0.4391 mL | 2.1954 mL | 4.3909 mL | |
| 10 mM | 0.2195 mL | 1.0977 mL | 2.1954 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.
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