LMI070

• CAT Number: I013780
• CAS Number: 1562338-42-4
• Molecular Formula: C₂₂H₂₇N₅O₂
• Molecular Weight: 393.48
• Purity: ≥95%
• Target: DNA/RNA Synthesis
• Solubility: DMSO: 6.12 mg/mL
• IUPAC Name: (6Z)-3-(1H-pyrazol-4-yl)-6-[3-(2,2,6,6-tetramethylpiperidin-4-yl)oxy-1H-pyridazin-6-ylidene]cyclohexa-2,4-dien-1-one
• InChI: InChI=1S/C22H27N5O2/c1-21(2)10-16(11-22(3,4)27-21)29-20-8-7-18(25-26-20)17-6-5-14(9-19(17)28)15-12-23-24-13-15/h5-9,12-13,16,25,27H,10-11H2,1-4H3,(H,23,24)/b18-17-
• InChIKey: YIFFDXMJVNKGBL-ZCXUNETKSA-N
• SMILES: CC1(CC(CC(N1)(C)C)OC2=NNC(=C3C=CC(=CC3=O)C4=CNN=C4)C=C2)C

LMI070 (NVS-SM1) is a highly potent, selective and orally active small molecule SMN2 splicing modulator.
Target: RNA splicing
in vitro: NVS-SM1 shows high plasma exposure, good bioavailability and, notably, good distribution to the brain, a primary target tissue NVS-SM1 exhibits efficacy at lower doses and exposures. NVS-SM1 shows robust activity across disease-relevant induced pluripotent stem cell (iPSc)-derived neurons. [1]
invivo : To evaluate the efficacy of NVS-SM1, we used the SMNΔ7 mouse model, which displays a severe phenotype. In the specific colony used for this study, death typically occurs before postnatal day 15. We were pleased to observe that, in addition to a dose-dependent elevation of SMN protein in the brain, oral administration of NVS-SM1 improved body weight and extended lifespan, with 50% of the animals in the 1 mg per kg body weight group and 62% of animals in the 3 mg per kg body weight group showing increased survival. [1]