BRANAPLAM HYDROCHLORIDE

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H27N5O2.ClH
Molecular Weight	429.943
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.CC1(C)CC(CC(C)(C)N1)OC2=NN=C(C=C2)C3=C(O)C=C(C=C3)C4=CNN=C4

InChI

InChIKey=XJIMIVJABPKGIY-UHFFFAOYSA-N

InChI=1S/C22H27N5O2.ClH/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);1H

HIDE SMILES / InChI

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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

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 846

C_max

Value	Dose	Analyte	Population
9.1 ng/mL CLINICAL TRIAL https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-002053-19/results	0.321 mg/kg single, oral dose: 0.321 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	LMI-070 plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN
18.6 ng/mL CLINICAL TRIAL https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-002053-19/results	0.654 mg/kg single, oral dose: 0.654 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	LMI-070 plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN
55.6 ng/mL CLINICAL TRIAL https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-002053-19/results	1.39 mg/kg single, oral dose: 1.39 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	LMI-070 plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN
53.2 ng/mL CLINICAL TRIAL https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-002053-19/results	2.49 mg/kg single, oral dose: 2.49 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	LMI-070 plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN
72.4 ng/mL CLINICAL TRIAL https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-002053-19/results	2.94 mg/kg single, oral dose: 2.94 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	LMI-070 plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
378 ng × h/mL CLINICAL TRIAL https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-002053-19/results	0.321 mg/kg single, oral dose: 0.321 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	LMI-070 plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN
892 ng × h/mL CLINICAL TRIAL https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-002053-19/results	0.654 mg/kg single, oral dose: 0.654 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	LMI-070 plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN
1820 ng × h/mL CLINICAL TRIAL https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-002053-19/results	1.39 mg/kg single, oral dose: 1.39 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	LMI-070 plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN
3310 ng × h/mL CLINICAL TRIAL https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-002053-19/results	2.49 mg/kg single, oral dose: 2.49 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	LMI-070 plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN
3800 ng × h/mL CLINICAL TRIAL https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-002053-19/results	2.94 mg/kg single, oral dose: 2.94 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	LMI-070 plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN

PubMed

Title	Date	PubMed
Discovery of Small Molecule Splicing Modulators of Survival Motor Neuron-2 (SMN2) for the Treatment of Spinal Muscular Atrophy (SMA).	2018-12-27	30407821
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).	2018-07-30	30061431
Small Molecules in Development for the Treatment of Spinal Muscular Atrophy.	2016-11-23	27490705

Substance Class	Chemical Created by `admin` on `Tue Apr 01 16:22:05 GMT 2025` Edited by `admin` on `Tue Apr 01 16:22:05 GMT 2025`
Record UNII	317C6VX21O
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LMI-070 HYDROCHLORIDE

Preferred Name

English

BRANAPLAM HYDROCHLORIDE

Official Name

English

BRANAPLAM HYDROCHLORIDE [USAN]

Common Name

English

LMI070 HYDROCHLORIDE

Code

English

5-(1H-PYRAZOL-4-YL)-2-(6-((2,2,6,6-TETRAMETHYLPIPERIDIN-4-YL)OXY)PYRIDAZIN-3-YL)PHENOL HYDROCHLORIDE

Systematic Name

English

NVP-LMI070-AAA

Code

English

PHENOL, 5-(1H-PYRAZOL-4-YL)-2-(6-((2,2,6,6-TETRAMETHYL-4-PIPERIDINYL)OXY)-3-PYRIDAZINYL)-, HYDROCHLORIDE (1:1)

Systematic Name

English

Code System Code Type Description

CAS

1562334-51-3