Parsaclisib

Parsaclisib is an inhibitor of PI3Kdelta (IC50 = 1 nM). It is selective for PI3Kdelta over PI3Kalpha, PI3Kbeta, and PI3Kgamma (IC50s = >10,000 nM for all), as well as a panel of 192 additional kinases and a panel of 70 ion channels and transporters at 1 µM. Parsaclisib inhibits the proliferation of primary human B cells (IC50 = 0.2 nM) and the production of cytokines in memory T cells (IC50s = 0.2-1.5 nM). It also inhibits the differentiation of naïve isolated human T cells into Th1, Th2, or Th17 T helper cells. It inhibits the proliferation of JeKo-1, Mino, Rec-1, and JVM-2 lymphoma cells (IC50s = 50s = 2-8 nM). In vivo, parsaclisib (0.1-10 mg/kg) reduces intratumoral phosphorylation of Akt and tumor growth in a Pfeiffer mouse xenograft model. Parsaclisib (3 mg/kg) reduces proteinuria, lymphadenopathy, and the severity of skin lesions in an MRL/MpJ-Fas lpr mouse model of spontaneous systemic lupus erythematosus (SLE). It also reduces salivary levels of TNF superfamily member 13B (TNFSF13B), also known as B cell activating factor (BAFF), and plasma levels of anti-SS-related antigen A (anti-SSA) and anti-SSB autoantibodies in a NOD.ShiLtJ mouse model of Sjögren's syndrome.Formal Name: (4R)-4-[3-[(1S)-1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-2-ethoxy-6-fluorophenyl]-2-pyrrolidinone. CAS Number: 1426698-88-5. Synonyms: INCB 050465. Molecular Formula: C20H22ClFN6O2. Formula Weight: 432.9. Purity: >95%. Formulation: (Request formulation change), A solid. Solubility: Acetonitrile: Slightly soluble: 0.1-1 mg/ml, DMSO: Sparingly soluble: 1-10 mg/ml. SMILES: NC1=C(C(C)=NN2[C@@H](C)C3=C(OCC)C([C@@]4([H])CC(NC4)=O)=C(F)C(Cl)=C3)C2=NC=N1. InChi Code: InChI=1S/C20H22ClFN6O2/c1-4-30-18-12(6-13(21)17(22)16(18)11-5-14(29)24-7-11)10(3)28-20-15(9(2)27-28)19(23)25-8-26-20/h6,8,10-11H,4-5,7H2,1-3H3,(H,24,29)(H2,23,25,26)/t10-,11-/m0/s1. InChi Key: ZQPDJCIXJHUERQ-QWRGUYRKSA-N.