LysRs-IN-2 (C09-1142-568)

LysRs-IN-2 is a lysyl-tRNA synthetase (KRS) inhibitor with IC 50 s of 0.015 μM and 0.13 μM for Plasmodium falciparum lysyl-tRNA synthetase ( Pf KRS) and Cryptosporidium parvum lysyl-tRNA synthetase ( Cp KRS), respectivelyIn VitroLysRs-IN-2 is active against whole-cell bloodstream P. falciparum 3D7 (EC 50 =0.27 μM), Hs KRS (IC 50 =1.8 μM), HepG2 cells (EC 50 =49 μM), and Cryptosporidium parvum (EC 50 =2.5 µM). MCE has not independently confirmed the accuracy of these methods. They are for reference only.In VivoLysRs-IN-2 (1.5 mg/kg; orally once a day for 4 days) reduces parasitemia by 90% in the murine P. falciparum SCID model. LysRs-IN-2 (20 mg/kg; orally once a day for 7 days) reduces parasite shedding in NOD SCID gamma mice and INF-γ-knockout mice ( Cryptosporidium mouse models) . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Murine P. falciparum NODscidIL2Rγ (SCID) model Dosage: 1.5 mg/kg Administration: Orally once a day for 4 days Result: Reduced parasitemia by 90% in the malaria SCID mouse model. Animal Model: NOD SCID gamma and INF-γ–knockout mouse models ( Cryptosporidium mouse models) Dosage: 20 mg/kg Administration: Orally once a day for 7 days Result: Reduced parasite shedding below detection level, and this reduction was sustained for 3 wk after treatment had stopped in INF-γ-knockout mice./nDosed orally at a concentration of 20 mg/kg once a day for 7 days showed 96% reduction of parasite shedding comparable to paromomycin in NOD SCID gamma mice.Form:SolidIC50& Target:IC50: 0.015 μM ( Pf KRS), 0.13 μM ( Cp KRS). Specification: 0.99 Molecular Formula: C17H16F3NO4 Molecular Weight: 355.31 PubChem CID: 134158252 Isomeric SMILES: C1CC(CCC1(CNC(=O)C2=CC(=O)C3=C(O2)C=CC(=C3)F)O)(F)F