Leniolisib-d₅  (Synonyms: CDZ173-d₅)

Leniolisib-d5 is a deuterated labeled Leniolisib^[1]. Leniolisib (CDZ173) is a potent and selective PI3Kδ inhibitor. Leniolisib has the potential for immunodeficiency disorders treatment.

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. Deuteration has gained attention because of its potential to affect the pharmacokinetic and metabolic profiles of drugs^[1].
Expression of APDS mutant p110δ in cell lines and patient-derived lymphocytes lead to increased pathway activity, measured as phosphorylation of AKT or S6, which is suppressed by leniolisib in a concentration dependent way^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

455.49

C₂₁H₂₀D₅F₃N₆O₂

COC1=C(C(F)(F)F)C=C(N2CC(C(N[C@H]3CCN(C(C([2H])([2H])C([2H])([2H])[2H])=O)C3)=NC=N4)=C4CC2)C=N1

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019 Feb;53(2):211-216.  [Content Brief]

  [2]. Hoegenauer K, et al. Discovery of CDZ173 (Leniolisib), Representing a Structurally Novel Class of PI3K Delta-Selective Inhibitors. ACS Med Chem Lett. 2017 Aug 25;8(9):975-980.  [Content Brief]

  [3]. Rao V, et al. Effective 'Activated PI3Kd Syndrome' -targeted therapy with PI3Kd inhibitor leniolisib. The New England journal of medicine: NEJM. ISSN 0028-4793; 1533-4406  [Content Brief]