| Field | Specification |
|---|---|
| Target | |
| CAS no. | |
| Applications | |
| Molecular weight | |
| Molecular formula | C21H29N5OS |
| Purity | |
| SMILES | |
| Form | Solid |
| Storage | |
| Shipping | |
| Catalog no. (Mfr.) | |
| Main SKU |
Compound Overview
MFN2 agonist-1 is an allosteric agonist of mitofusin 2 (MFN2), with an EC50 of 3 nM. It mimics the MFN2 HR1 peptide to compete for HR2, disrupting the HR1-HR2 autoinhibitory interaction, stabilizing the open conformation of MFN2, and promoting GTP hydrolysis and mitochondrial fusion; its activity depends on endogenous MFN1 or MFN2 and does not impair cell viability. It reverses mitochondrial fragmentation, depolarization, aggregation, and axonal transport defects, restores bidirectional movement, and improves enhanced autophagy, and it has been used in studies of Charcot-Marie-Tooth disease type 2A, Alzheimer's disease, Parkinson's disease, and Huntington's disease[1]. It is supplied as a white to off-white solid (C21H29N5OS, MW 399.55) at 98.84% purity.
Physical & Chemical Properties
| CAS Number | 2230047-87-5 |
|---|---|
| Molecular Formula | C21H29N5OS |
| Molecular Weight | 399.55 g/mol |
| Purity | 98.84% |
| Appearance | Solid |
| Color | White to off-white |
| SMILES | O=C(NC1C(C)CCCC1)NCCSC2=NN=C(C3CC3)N2C4=CC=CC=C4 |
| Target | MFN2 |
| Signaling Pathway | Metabolic Enzyme/Protease |
| Solubility | In Vitro: DMSO: 50 mg/mL (125.14 mM; Requires sonication and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO) |
| Storage | Powder: -20°C, 3 years; 4°C, 2 years. In solvent: -80°C, 6 months; -20°C, 1 month. |
| Shipping | Room temperature in continental US; may vary elsewhere. |
Biological Activity
IC50 & Target[1]
|
MFN2 3 nM (EC50) |
Literature Cited
Sources cited in this description and in the In Vitro & In Vivo Data tab. Peer-reviewed publications that used this product are listed under References.
Safety
For Research Use Only. Not for use in diagnostic or therapeutic procedures, and not for human or veterinary use. Handle in accordance with the Safety Data Sheet and your institution's chemical hygiene plan.
In Vitro
| Solvent | Solubility | Notes |
|---|---|---|
| DMSO | 50 mg/mL (125.14 mM) | requires sonication and warming and heat to 60°C; use freshly opened DMSO (absorbed moisture lowers solubility) |
Aliquot the stock solution and store it at -80°C (up to 6 months) or -20°C (up to 1 month); avoid repeated freeze-thaw cycles.
Data provided by the manufacturer.
In Vitro
In MFN1-/- MFN2-/- mouse embryonic fibroblasts (MEFs), MFN2 agonist-1 (B-A/l) (0.1 nM-10 μM) potently stimulates mitochondrial fusion, with an EC50 of 3 nM[1]. From the MFN2 HR2 domain, MFN2 agonist-1 (0.01 nM-10 μM) displaces the MFN2 HR1 peptide (374-384), with an IC50 of 150 nM[1]. Mitochondrial fusion is restored by MFN2 agonist-1 in MFN2-/- MEFs that express the CMT2A mutant MFN2 T105M[1]. Reduced FRET signals confirm that MFN2 agonist-1 induces MFN2 to adopt an open, fusion-permissive conformation in isolated mitochondria and intact cells[1]. Through activation of endogenous MFN1, MFN2 agonist-1 corrects the mitochondrial fragmentation and depolarization in MFN1+/+ MFN2-/- MEFs that express the CMT2A mutants MFN2R94Q or MFN2K109A[1]. In primary cultured neonatal mouse neurons that express the CMT2A mutant MFN2R94Q, MFN2 agonist-1 reverses mitochondrial fragmentation as well as the decrease in mitochondrial membrane potential[1]. MFN2 agonist-1 (10-60 min post-administration) restores motility and velocity of axonal mitochondria in ex vivo sciatic nerves of MFN2T105M mice[1]. In cultured neonatal mouse neurons that express the CMT2A mutant MFN2T105M, MFN2 agonist-1 restores mitochondrial transport, function and morphology[1].
Data provided by the manufacturer. Numbered citations refer to the Literature Cited list in the product description.
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