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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
Structure of BRANAPLAM

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)

HIDE SMILES / InChI

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.

Approval Year

PubMed

PubMed

TitleDatePubMed
Discovery of Small Molecule Splicing Modulators of Survival Motor Neuron-2 (SMN2) for the Treatment of Spinal Muscular Atrophy (SMA).
2018 Dec 27
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
by admin
on Thu Jul 06 16:22:13 UTC 2023
Edited
by admin
on Thu Jul 06 16:22:13 UTC 2023
Record UNII
P12R69543A
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
BRANAPLAM
INN   WHO-DD  
USAN   INN  
Official Name English
NVS-SM1
Code English
PHENOL, 5-(1H-PYRAZOL-4-YL)-2-(6-((2,2,6,6-TETRAMETHYL-4-PIPERIDINYL)OXY)-3-PYRIDAZINYL)-
Systematic Name English
branaplam [INN]
Common Name English
5-(1H-PYRAZOL-4-YL)-2-(6-((2,2,6,6-TETRAMETHYLPIPERIDIN-4-YL)OXY)PYRIDAZIN-3-YL)PHENOL
Systematic Name English
NVP-LMI070-NX
Code English
LMI070
Code English
Branaplam [WHO-DD]
Common Name English
BRANAPLAM [USAN]
Common Name English
LMI-070
Code English
Classification Tree Code System Code
FDA ORPHAN DRUG 620117
Created by admin on Thu Jul 06 16:22:13 UTC 2023 , Edited by admin on Thu Jul 06 16:22:13 UTC 2023
FDA ORPHAN DRUG 773320
Created by admin on Thu Jul 06 16:22:13 UTC 2023 , Edited by admin on Thu Jul 06 16:22:13 UTC 2023
EU-Orphan Drug EU/3/18/2010
Created by admin on Thu Jul 06 16:22:13 UTC 2023 , Edited by admin on Thu Jul 06 16:22:13 UTC 2023
Code System Code Type Description
PUBCHEM
135565042
Created by admin on Thu Jul 06 16:22:13 UTC 2023 , Edited by admin on Thu Jul 06 16:22:13 UTC 2023
PRIMARY
DRUG BANK
DB14918
Created by admin on Thu Jul 06 16:22:13 UTC 2023 , Edited by admin on Thu Jul 06 16:22:13 UTC 2023
PRIMARY
SMS_ID
100000174622
Created by admin on Thu Jul 06 16:22:13 UTC 2023 , Edited by admin on Thu Jul 06 16:22:13 UTC 2023
PRIMARY
WIKIPEDIA
Branaplam
Created by admin on Thu Jul 06 16:22:13 UTC 2023 , Edited by admin on Thu Jul 06 16:22:13 UTC 2023
PRIMARY
USAN
JK-244
Created by admin on Thu Jul 06 16:22:13 UTC 2023 , Edited by admin on Thu Jul 06 16:22:13 UTC 2023
PRIMARY
MANUFACTURER PRODUCT INFORMATION
BRANAPLAM
Created by admin on Thu Jul 06 16:22:13 UTC 2023 , Edited by admin on Thu Jul 06 16:22:13 UTC 2023
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.
INN
10380
Created by admin on Thu Jul 06 16:22:13 UTC 2023 , Edited by admin on Thu Jul 06 16:22:13 UTC 2023
PRIMARY
EPA CompTox
DTXSID801337133
Created by admin on Thu Jul 06 16:22:13 UTC 2023 , Edited by admin on Thu Jul 06 16:22:13 UTC 2023
PRIMARY
NCI_THESAURUS
C174824
Created by admin on Thu Jul 06 16:22:13 UTC 2023 , Edited by admin on Thu Jul 06 16:22:13 UTC 2023
PRIMARY
CAS
1562338-42-4
Created by admin on Thu Jul 06 16:22:13 UTC 2023 , Edited by admin on Thu Jul 06 16:22:13 UTC 2023
PRIMARY
FDA UNII
P12R69543A
Created by admin on Thu Jul 06 16:22:13 UTC 2023 , Edited by admin on Thu Jul 06 16:22:13 UTC 2023
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
Related Record Type Details
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.