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| 25mg |
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Purity: ≥98%
Leniolisib (formerly CDZ173; CDZ-173; Joenja) is a novel, potent and selective PI3K (phosphatidylinositol 3-kinase inhibitor) inhibitor with immunomodulatory effects. With IC50 values for PI3K of 0.244, 0.424, 2.23, and 0.011 M, PI3K, PI3K, PI3K, and PI3K, respectively, it inhibits PI3K. Clinical trials for the treatment of immunodeficiency disorders are currently in phase II/III. Ex vivo measurements of the PI3K/AKT pathway activity were reduced in a dose-dependent manner by oral leniolisib, which also improved immune dysregulation. The specific inhibition of PI3K as a promising new targeted therapy in APDS and other diseases characterized by overactivation of the PI3K pathway is supported by leniolisib's well-tolerated side effects and improved laboratory and clinical parameters in APDS. ClinicalTrials.gov records this trial under the identifier #NCT02435173. It was given FDA approval in March 2023 to treat the uncommon primary immunodeficiency known as activated phosphoinositide 3-kinase delta syndrome (APDS).
| Targets |
PI3Kδ ( IC50 = 11 nM); PI3Kα ( IC50 = 280 nM); PI3Kβ ( IC50 = 480 nM); PI3Kγ ( IC50 = 2.57 μM); DNA-PK ( IC50 = 880 nM)
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| ln Vitro |
Leniolisib inhibits phosphorylation of AKT or S6, a pathway activity indicator that is elevated when APDS mutant p110 is expressed in cell lines and patient-derived lymphocytes, in a concentration-dependent manner[1].
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| ln Vivo |
The immune dysregulation is resolved by oral leniolisib, which also results in a dose-dependent decrease in PI3K/AKT pathway activity, normalization of circulating transitional and naive B cells, and a decrease in PD-1+CD4+ and senescent CD57+CD8+ T cells. All patients exhibit improvement in lymphoproliferation after 12 weeks of therapy, with decreases in lymph node sizes and spleen volumes of 39% (mean, range, 26-57%) and 40% (mean, range, 13-65%), respectively[1].
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| References |
| Molecular Formula |
C21H25F3N6O2
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| Molecular Weight |
450.47
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| Exact Mass |
450.2
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| Elemental Analysis |
C, 55.99; H, 5.59; F, 12.65; N, 18.66; O, 7.10
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| CAS # |
1354690-24-6
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| Related CAS # |
Leniolisib phosphate;1354691-97-6
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| Appearance |
Solid powder
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| SMILES |
FC(C1=C(OC)N=CC(N(CCC2=NC=N3)CC2=C3N[C@@H]4CN(C(CC)=O)CC4)=C1)(F)F
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| InChi Key |
MWKYMZXCGYXLPL-ZDUSSCGKSA-N
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| InChi Code |
InChI=1S/C21H25F3N6O2/c1-3-18(31)30-6-4-13(10-30)28-19-15-11-29(7-5-17(15)26-12-27-19)14-8-16(21(22,23)24)20(32-2)25-9-14/h8-9,12-13H,3-7,10-11H2,1-2H3,(H,26,27,28)/t13-/m0/s1
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| Chemical Name |
(S)-1-(3-((6-(6-methoxy-5-(trifluoromethyl)pyridin-3-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)amino)pyrrolidin-1-yl)propan-1-one
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.55 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.55 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.55 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2199 mL | 11.0995 mL | 22.1990 mL | |
| 5 mM | 0.4440 mL | 2.2199 mL | 4.4398 mL | |
| 10 mM | 0.2220 mL | 1.1100 mL | 2.2199 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.
| NCT Number | Status | Interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT05693129 | Not yet recruiting | Drug: Leniolisib | APDS | Pharming Technologies B.V. | August 30, 2023 | Phase 3 |
| NCT05438407 | Rrecruiting | Drug: Leniolisib | APDS | Pharming Technologies B.V. | February 1, 2023 | Phase 3 |
Effective “activated PI3Kδ syndrome”–targeted therapy with the PI3Kδ inhibitor leniolisib.Blood.2017 Nov 23;130(21):2307-2316. |
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PIK3CDmutant transfectants treated with leniolisib or an mTOR inhibitor.Blood.2017 Nov 23;130(21):2307-2316. |
T-cell blast activation in presence or absence of leniolisib.Blood.2017 Nov 23;130(21):2307-2316. |
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