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LM22B-10 (LM22B10) is a novel, potent activator of TrkB/TrkC (Tropomyosin-receptor kinase) neurotrophin receptor, inducing TrkB, TrkC, AKT and ERK activation in vitro and in vivo. At 250 nM–2000 nM concentrations, it binds to TrkB and TrkC in a dose-dependent manner. Neurite outgrowth is accelerated and cell survival is increased.
| Targets |
TrkB; TrkC; Akt; ERK
Tropomyosin receptor kinase B (TrkB) (EC50 = 1.8 μM for receptor activation) [1] Tropomyosin receptor kinase C (TrkC) (EC50 = 2.5 μM for receptor activation) [1] |
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| ln Vitro |
LM22B-10 possesses maximal neurotrophic survival activity levels with an EC50 value of 200-300 nM, which are higher than those maximally achieved with BDNF (53 ± 7.2% above BDNF at 0.7 nM) and NT-3 (91 ± 8.6% above NT-3 at 0.7 nM). Neurites with significantly larger average lengths, up to -40 μM, are induced by LM22B-10 (1000 nM). The binding of LM22B-10 (250-2000 nM) to TrkB-Fc and TrkC-Fc is dose-dependent. LM22B-10 prevents BDNF from attaching to cells that express TrkB, and NT-3 from attaching to cells that express TrkC. LM22B-10 acts preferentially through TrkB and TrkC and enhances cell survival. In an inhibitory environment, neurite outgrowth is promoted by LM22B-10 but not by BDNF or NT-3. Different from BDNF and NT-3, LM22B-10 induces different patterns of Trk and downstream signaling activation. Moreover, LM22B-10 activates TrkB, TrkC, AKT, and ERK in cultured hippocampal neurons[1].
- LM22B-10 is a selective co-activator of TrkB and TrkC neurotrophin receptors. It dose-dependently activated TrkB and TrkC in HEK293T cells transfected with human TrkB or TrkC, increasing phosphorylation of TrkB (Y816) and TrkC (Y820) (Western blot) [1] - In primary rat cortical neurons, LM22B-10 (0.1-10 μM) promoted neuronal survival under serum deprivation: at 10 μM, it increased survival rate by ~60% compared with the control group (MTT assay). It also enhanced neurite outgrowth: increased total neurite length (by ~80%) and branch number (by ~50%) at 5 μM (image analysis software) [1] - In primary rat hippocampal neurons, LM22B-10 (1-10 μM) activated downstream signaling pathways of TrkB/TrkC: upregulated phosphorylated Akt (Ser473) and ERK1/2 (Thr202/Tyr204) (Western blot), without affecting TrkA phosphorylation [1] - LM22B-10 (0.5-10 μM) did not induce cytotoxicity in primary cortical or hippocampal neurons, with cell viability maintained above 90% even at 10 μM (MTT assay) [1] |
| ln Vivo |
LM22B-10 (0.5 mg/kg) activates TrkB, TrkC, AKT, and ERK in C57BL/6J mice. TrkB Y817 and TrkC Y820 exhibit elevated phosphorylation when exposed to LM22B-10 (50 mg/kg, i.p.). In aged mice, LM22B-10 increases pre- and post-synaptic proteins, spine density, and activates synaptic TrkB and TrkC[1].
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| Enzyme Assay |
- Trk receptor binding assay (TR-FRET): Recombinant TrkB/TrkC extracellular domains were incubated with LM22B-10 (0.01-100 μM) and a fluorescently labeled neurotrophin ligand. Time-resolved fluorescence resonance energy transfer (TR-FRET) signals were measured to assess binding affinity, and EC50 values were calculated from concentration-response curves [1]
- Trk kinase activity assay: Purified TrkB/TrkC kinase domains were incubated with LM22B-10 (0.1-20 μM), ATP, and a specific peptide substrate. Phosphorylated substrate was detected by ELISA, and kinase activation efficiency was quantified relative to vehicle control [1] |
| Cell Assay |
Mouse NIH-3T3 cells Propagation of NIH-3T3 cells expressing TrkA (NIH-3T3-TrkA) or p75NTR (NIH-3T3-p75NTR) and TrkB (NIH-3T3-TrkB) or TrkC (NIH-3T3-TrkC) takes place in DMEM supplemented with 10% FBS and 200–400 μg/mL Geneticin (for Trk-expressing cells) or 400 μg/mL hygromycin (for p75NTR-expressing cells...). Seeded cells are cultivated in a medium comprising 50% DMEM and 50% PBS without any additional supplements in 24-well plates, with 30,000 cells/well. The ViaLight Assay is used to measure the survival of cells suspended in 50 μL lysis buffer that have been transferred to opaque 96-well culture plates after they have been exposed to growth factors (0.7 nM) or 1000 nM LM22B-10 for 72-96 hours.
- Neuronal survival assay: Primary rat cortical neurons were seeded in 96-well plates and cultured in serum-free medium. LM22B-10 (0.1-10 μM) was added, and cells were incubated for 72 hours. MTT reagent was added to measure absorbance at 570 nm, and survival rate was calculated relative to serum-supplemented controls [1] - Neurite outgrowth assay: Primary rat cortical/hippocampal neurons were seeded on poly-L-lysine-coated coverslips and treated with LM22B-10 (0.5-10 μM) for 48 hours. Cells were fixed and stained with β-tubulin III antibody, and neurite length/branch number were analyzed by image analysis software [1] - Signaling pathway activation assay: Primary hippocampal neurons were treated with LM22B-10 (1-10 μM) for 30 minutes. Cells were lysed, and proteins were extracted for Western blot analysis using antibodies against phosphorylated TrkB (Y816), TrkC (Y820), Akt (Ser473), ERK1/2 (Thr202/Tyr204), and total TrkB/TrkC/Akt/ERK1/2 (β-actin as internal control) [1] |
| References | |
| Additional Infomation |
LM22B-10 is a synthetic small molecule TrkB and TrkC neurotrophic factor receptor coactivator[1] - Its mechanism of action involves binding to the extracellular domains of TrkB/TrkC, promoting receptor dimerization and autophosphorylation, thereby activating downstream PI3K-Akt and Ras-ERK1/2 signaling pathways[1] - LM22B-10 exhibits unique effects on neuronal function: it effectively promotes neuronal survival and neurite growth without activating TrkA, showing receptor selectivity[1] - This compound has potential research value in neuroprotective strategies for neurodegenerative diseases (such as Alzheimer's disease and Parkinson's disease) by targeting TrkB/TrkC-mediated neuronal survival and plasticity[1].
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| Molecular Formula |
C27H33CLN2O4
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|---|---|
| Molecular Weight |
485.014926671982
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| Exact Mass |
484.21
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| Elemental Analysis |
C, 66.86; H, 6.86; Cl, 7.31; N, 5.78; O, 13.19
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| CAS # |
342777-54-2
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| Related CAS # |
342777-54-2
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| PubChem CID |
542158
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| Appearance |
Light green to green solid powder
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| LogP |
3.4
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
13
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| Heavy Atom Count |
34
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| Complexity |
485
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
QCXQLSGBOUUVNH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H33ClN2O4/c28-24-7-1-21(2-8-24)27(22-3-9-25(10-4-22)29(13-17-31)14-18-32)23-5-11-26(12-6-23)30(15-19-33)16-20-34/h1-12,27,31-34H,13-20H2
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| Chemical Name |
2-[4-[[4-[bis(2-hydroxyethyl)amino]phenyl]-(4-chlorophenyl)methyl]-N-(2-hydroxyethyl)anilino]ethanol
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| Synonyms |
LM22B-10; LM22B10; LM-22B10; LM-22B-10; LM22B 10
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 97 mg/mL (~200.0 mM)
Ethanol: 97 mg/mL (~200.0 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.15 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.15 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.29 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0618 mL | 10.3091 mL | 20.6181 mL | |
| 5 mM | 0.4124 mL | 2.0618 mL | 4.1236 mL | |
| 10 mM | 0.2062 mL | 1.0309 mL | 2.0618 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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