LMI070
LMI070 Basic information
- Product Name:
- LMI070
- Synonyms:
-
- NVS-SM1, Branaplam
- LMI070
- NVS-SM1
- NVS-SM1; LMI-070;
- LMI070 (Branaplam)
- Branaplam
- LMI070 (NVS-SM1)
- 5-(1H-pyrazol-4-yl)-2-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)phenol
- CAS:
- 1562338-42-4
- MF:
- C22H27N5O2
- MW:
- 393.48
- Mol File:
- 1562338-42-4.mol
LMI070 Chemical Properties
- Boiling point:
- 660.0±55.0 °C(Predicted)
- Density
- 1.171±0.06 g/cm3(Predicted)
- storage temp.
- Store at -20°C
- solubility
- DMSO:3.0(Max Conc. mg/mL);7.62(Max Conc. mM)
- form
- A crystalline solid
- pka
- 7.84±0.40(Predicted)
- color
- White to yellow
- InChI
- 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)
- InChIKey
- STWTUEAWRAIWJG-UHFFFAOYSA-N
- SMILES
- C1(O)=CC(C2=CNN=C2)=CC=C1C1=NN=C(OC2CC(C)(C)NC(C)(C)C2)C=C1
LMI070 Usage And Synthesis
Uses
Branaplam (LMI070; NVS-SM1) is a highly potent, selective and orally active survival motor neuron-2 (SMN2) splicing modulator with an EC50 of 20 nM for SMN. Branaplam inhibits human-ether-a-go-go-related gene (hERG) with an IC50 of 6.3 μM. Branaplam elevates full-length SMN protein and extends survival in a severe spinal muscular atrophy (SMA) mouse model[1][2].
in vivo
Branaplam (LMI070; NVS-SM1; 3, 10, 30 mg/kg; oral) produces dose-dependent elevations of SMN2-FL transcript and SMN protein in brain and spinal cord[1].
?
Branaplam (1 mg/kg of IV; 3 mg/kg of PO) has a CL of 25 mL/min/kg and an AUC of 3.03 μM?h[2].
?
A single Branaplam (oral; 30 mg/kg) results in significant and durable SMN protein elevation in brain for up to 160 hours in C/+ mice[1].
?
Branaplam (oral; 0.03, 0.1, 0.3, 1, 3 mg/kg) improves body weight and extendes lifespan in n SMNΔ7 mice[1].
| Animal Model: | C/+ SMA mouse model[1] |
| Dosage: | 3, 10, 30 mg/kg |
| Administration: | Oral |
| Result: | Produced dose-dependent elevations of SMN2-FL transcript and SMN protein in brain and spinal cord. |
| Animal Model: | Male Sprague-Dawley rat[2] |
| Dosage: | 1 mg/kg (IV);3 mg/kg (PO) (Pharmacokinetic Analysis) |
| Administration: | IV or PO |
| Result: | Had a CL of 25 mL/min/kg and an AUC of 3.03 μM?h. |
References
[1] Palacino J, et al. SMN2 splice modulators enhance U1-pre-mRNA association and rescue SMA mice. Nat Chem Biol. 2015 Jul;11(7):511-517. DOI:10.1038/nchembio.1837
[2] Cheung AK, et al. Discovery of Small Molecule Splicing Modulators of Survival Motor Neuron-2 (SMN2) for the Treatment of Spinal Muscular Atrophy (SMA). J Med Chem. 2018 Dec 27;61(24):11021-11036. DOI:10.1021/acs.jmedchem.8b01291
LMI070Supplier
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- +86-21-20908456
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