Leniolisib (CDZ173)

Cas No.:	1354690-24-6
Chemical Name:	Leniolisib
Synonyms:	Leniolisib;CDZ173;L22772Z9CP;(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;Leniolisib [INN];Leniolisib (CDZ173);Leniolisib (USAN/INN);CDZ173-NX;GTPL9424;MWKYMZXCGYXLPL-ZDUSSCGKSA-N;BDBM118299;SB18839;Example 67 [WO2012004299];1-{(S)-3-[6-(6-methoxy-5-trifluoromethyl-pyridin-3-yl)-5,6,7,8-tetrahydro-pyrido[4,3-d];Leniolisib free base;1-[(3S)-3-[[6-[6-methoxy-5-(trifluoromethyl)pyridin-3-yl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-4-yl]amino]pyrrolidin-1-yl]propan-1-one;Cdz173 free base;Leniolisib; CDZ173;C
SMILES:	FC(C1=C(N=C([H])C(=C1[H])N1C([H])([H])C([H])([H])C2=C(C1([H])[H])C(=NC([H])=N2)N([H])[C@]1([H])C([H])([H])N(C(C([H])([H])C([H])([H])[H])=O)C([H])([H])C1([H])[H])OC([H])([H])[H])(F)F
Formula:	C21H25F3N6O2
M.Wt:	450.4574
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	Leniolisib (CDZ173) is a potent and selective PI3Kδ inhibitor currently in phase II/III clinical trials for the treatment of immunodeficiency disorders.
In 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 naïve 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[1].
In Vitro:	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[1].
References:	[1]. 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