Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C22H27N5O2 |
| Molecular Weight | 393.4821 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CC1(C)CC(CC(C)(C)N1)OC2=CC=C(N=N2)C3=CC=C(C=C3O)C4=CNN=C4
InChI
InChIKey=STWTUEAWRAIWJG-UHFFFAOYSA-N
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/h5-9,12-13,16,27-28H,10-11H2,1-4H3,(H,23,24)
| Molecular Formula | C22H27N5O2 |
| Molecular Weight | 393.4821 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
LMI-070 is an experimental compound being developed by Novartis Pharma as a treatment for spinal muscular atrophy (SMA). It is a small-molecule drug which modifies alternative splicing of the SMN2 gene, bringing about increased levels of SMN protein. LMI-070 originated from a high-throughput phenotypic screening hit, pyridazine 2, and evolved via multiparameter lead optimization. In a severe mouse SMA model, LMI-070 treatment increased full-length SMN RNA and protein levels, and extended survival. LMI-070 is taken orally, usually in a liquid form once a week. It is in phase II clinical trial.
Originator
Approval Year
PubMed
| Title | Date | PubMed |
|---|---|---|
| Small Molecules in Development for the Treatment of Spinal Muscular Atrophy. | 2016 Nov 23 |
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| Discovery of Small Molecule Splicing Modulators of Survival Motor Neuron-2 (SMN2) for the Treatment of Spinal Muscular Atrophy (SMA). | 2018 Dec 27 |
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| Protocol for a phase II, monocentre, double-blind, placebo-controlled, cross-over trial to assess efficacy of pyridostigmine in patients with spinal muscular atrophy types 2-4 (SPACE trial). | 2018 Jul 30 |
| Substance Class |
Chemical
Created
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admin
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Edited
Sat Dec 16 10:47:16 GMT 2023
by
admin
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Sat Dec 16 10:47:16 GMT 2023
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| Record UNII |
P12R69543A
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| Record Status |
Validated (UNII)
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FDA ORPHAN DRUG |
620117
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FDA ORPHAN DRUG |
773320
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EU-Orphan Drug |
EU/3/18/2010
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135565042
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DB14918
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JK-244
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BRANAPLAM
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PRIMARY | LMI070 (NVS-SM1) is a highly potent, selective and orally active small molecule SMN2 splicing modulator.Target: RNA splicingin 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.in vivo : To evaluate the efficacy of NVS-SM1, we used the SMN.DELTA.7 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. | ||
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ACTIVE MOIETY |
Drug: LMI 070(Primary); Indication: Spinal muscular atrophy; Focus: Adverse reactions, First in man, Proof of concept; Sponsor: Novartis; Most Recent Events: 20 Jul 2016 The trial has been temporarily halted in Germany., 09 Jun 2016 The trial has been temporarily halted in Denmark., 31 May 2016 The trial was temporarily halted in Italy.
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