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=NN=C(C=C2)C3=C(O)C=C(C=C3)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
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
9.1 ng/mL |
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 |
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 |
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 |
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 |
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 | Co-administered | Analyte | Population |
|---|---|---|---|---|
378 ng × h/mL |
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 |
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 |
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 |
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 |
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 |
|
| 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 |
|
| Small Molecules in Development for the Treatment of Spinal Muscular Atrophy. | 2016-11-23 |
| Substance Class |
Chemical
Created
by
admin
on
Edited
Mon Mar 31 23:26:31 GMT 2025
by
admin
on
Mon Mar 31 23:26:31 GMT 2025
|
| Record UNII |
P12R69543A
|
| Record Status |
Validated (UNII)
|
| Record Version |
|
-
Download
| Name | Type | Language | ||
|---|---|---|---|---|
|
Preferred Name | English | ||
|
Official Name | English | ||
|
Systematic Name | English | ||
|
Common Name | English | ||
|
Systematic Name | English | ||
|
Code | English | ||
|
Code | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Code | English |
| Classification Tree | Code System | Code | ||
|---|---|---|---|---|
|
FDA ORPHAN DRUG |
620117
Created by
admin on Mon Mar 31 23:26:31 GMT 2025 , Edited by admin on Mon Mar 31 23:26:31 GMT 2025
|
||
|
FDA ORPHAN DRUG |
773320
Created by
admin on Mon Mar 31 23:26:31 GMT 2025 , Edited by admin on Mon Mar 31 23:26:31 GMT 2025
|
||
|
EU-Orphan Drug |
EU/3/18/2010
Created by
admin on Mon Mar 31 23:26:31 GMT 2025 , Edited by admin on Mon Mar 31 23:26:31 GMT 2025
|
| Code System | Code | Type | Description | ||
|---|---|---|---|---|---|
|
135565042
Created by
admin on Mon Mar 31 23:26:31 GMT 2025 , Edited by admin on Mon Mar 31 23:26:31 GMT 2025
|
PRIMARY | |||
|
DB14918
Created by
admin on Mon Mar 31 23:26:31 GMT 2025 , Edited by admin on Mon Mar 31 23:26:31 GMT 2025
|
PRIMARY | |||
|
100000174622
Created by
admin on Mon Mar 31 23:26:31 GMT 2025 , Edited by admin on Mon Mar 31 23:26:31 GMT 2025
|
PRIMARY | |||
|
Branaplam
Created by
admin on Mon Mar 31 23:26:31 GMT 2025 , Edited by admin on Mon Mar 31 23:26:31 GMT 2025
|
PRIMARY | |||
|
JK-244
Created by
admin on Mon Mar 31 23:26:31 GMT 2025 , Edited by admin on Mon Mar 31 23:26:31 GMT 2025
|
PRIMARY | |||
|
BRANAPLAM
Created by
admin on Mon Mar 31 23:26:31 GMT 2025 , Edited by admin on Mon Mar 31 23:26:31 GMT 2025
|
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. | ||
|
10380
Created by
admin on Mon Mar 31 23:26:31 GMT 2025 , Edited by admin on Mon Mar 31 23:26:31 GMT 2025
|
PRIMARY | |||
|
DTXSID801337133
Created by
admin on Mon Mar 31 23:26:31 GMT 2025 , Edited by admin on Mon Mar 31 23:26:31 GMT 2025
|
PRIMARY | |||
|
C174824
Created by
admin on Mon Mar 31 23:26:31 GMT 2025 , Edited by admin on Mon Mar 31 23:26:31 GMT 2025
|
PRIMARY | |||
|
1562338-42-4
Created by
admin on Mon Mar 31 23:26:31 GMT 2025 , Edited by admin on Mon Mar 31 23:26:31 GMT 2025
|
PRIMARY | |||
|
P12R69543A
Created by
admin on Mon Mar 31 23:26:31 GMT 2025 , Edited by admin on Mon Mar 31 23:26:31 GMT 2025
|
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.
|
