BRANAPLAM

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National Institutes of Health Divider Arrow

NCATS

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

Structure Search

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

Description
Sources: https://www.treatsma.uk/treatments/branaplam/ | https://adisinsight.springer.com/drugs/800041467 | https://www.ncbi.nlm.nih.gov/pubmed/30407821

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

Targets

Targets

Primary Target	Pharmacology	Condition	Potency
Survival motor neuron protein 2 Target ID: CHEMBL1293232 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26030728 \| https://smanewstoday.com/lmi070-novartis \| http://www.sma-europe.eu/clinical-trials/modulation-of-the-smn2-back-up-gene-small-molecules/novartis-small-molecule-branaplam-lmi070/ \| http://www.ema.europa.eu/docs/en_GB/document_library/Orphan_designation/2018/05/WC500249083.pdf	Modulator 828

PubMed

PubMed

Title	Date	PubMed

Substance Class	Chemical Created by `admin` on `Sat Dec 16 10:47:16 GMT 2023` Edited by `admin` on `Sat Dec 16 10:47:16 GMT 2023`
Record UNII	P12R69543A
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

BRANAPLAM

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 Sat Dec 16 10:47:16 GMT 2023 , Edited by admin on Sat Dec 16 10:47:16 GMT 2023

FDA ORPHAN DRUG

773320

Created by admin on Sat Dec 16 10:47:16 GMT 2023 , Edited by admin on Sat Dec 16 10:47:16 GMT 2023

EU-Orphan Drug

EU/3/18/2010

Created by admin on Sat Dec 16 10:47:16 GMT 2023 , Edited by admin on Sat Dec 16 10:47:16 GMT 2023

Code System Code Type Description

PUBCHEM

135565042

Created by admin on Sat Dec 16 10:47:16 GMT 2023 , Edited by admin on Sat Dec 16 10:47:16 GMT 2023

PRIMARY

DRUG BANK

DB14918

Created by admin on Sat Dec 16 10:47:16 GMT 2023 , Edited by admin on Sat Dec 16 10:47:16 GMT 2023

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SMS_ID

100000174622

Created by admin on Sat Dec 16 10:47:16 GMT 2023 , Edited by admin on Sat Dec 16 10:47:16 GMT 2023

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WIKIPEDIA

Branaplam

Created by admin on Sat Dec 16 10:47:16 GMT 2023 , Edited by admin on Sat Dec 16 10:47:16 GMT 2023

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USAN

JK-244

Created by admin on Sat Dec 16 10:47:16 GMT 2023 , Edited by admin on Sat Dec 16 10:47:16 GMT 2023

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MANUFACTURER PRODUCT INFORMATION

BRANAPLAM

Created by admin on Sat Dec 16 10:47:16 GMT 2023 , Edited by admin on Sat Dec 16 10:47:16 GMT 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 Sat Dec 16 10:47:16 GMT 2023 , Edited by admin on Sat Dec 16 10:47:16 GMT 2023

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EPA CompTox

DTXSID801337133

Created by admin on Sat Dec 16 10:47:16 GMT 2023 , Edited by admin on Sat Dec 16 10:47:16 GMT 2023

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NCI_THESAURUS

C174824

Created by admin on Sat Dec 16 10:47:16 GMT 2023 , Edited by admin on Sat Dec 16 10:47:16 GMT 2023

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CAS

1562338-42-4

Created by admin on Sat Dec 16 10:47:16 GMT 2023 , Edited by admin on Sat Dec 16 10:47:16 GMT 2023

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FDA UNII

P12R69543A

Created by admin on Sat Dec 16 10:47:16 GMT 2023 , Edited by admin on Sat Dec 16 10:47:16 GMT 2023

PRIMARY

Related Record Type Details


					317C6VX21O

BRANAPLAM HYDROCHLORIDE

SALT/SOLVATE -> PARENT

Amount:

Related Record Type Details


					P12R69543A

BRANAPLAM

ACTIVE MOIETY

Comments:

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.

Amount: