| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
Purity: ≥98%
LY-344864 HCl, the hydrochloride salt of LY344864, is a novel, potent and selective receptor agonist of 5-HT1F with Ki of 6 nM. The 56 additional serotonergic and non-serotonergic neuronal binding sites that were analyzed revealed minimal affinity for it. A full agonist with an effect comparable to serotonin itself, LY344864 was demonstrated to be.
| Targets |
human 5-HT1F Receptor ( Ki = 0.006 μM ); human 5-HT1A Receptor ( Ki = 0.530 μM ); human 5-HT1B Receptor ( Ki = 0.549 μM ); human 5-HT1D Receptor ( Ki = 0.575 μM ); human 5-HT1E Receptor ( Ki = 1.415 μM ); human 5-HT2B Receptor ( Ki = 1.695 μM ); Human 5-HT2C Receptor ( Ki = 3.499 μM ); Human 5-HT3A Receptor ( Ki = 3.935 μM ); rat α2-adrenergic receptor ( Ki = 3.69 μM ); rat α1-adrenergic receptor ( Ki = 5.06 μM ); Human 5-HT7 Receptor ( Ki = 4.851 μM )
5-HT1F receptor (selective agonist, binding affinity Ki = 6 nM, EC50 = 3 nM) [2] |
|---|---|
| ln Vitro |
LY 344864 binds to human 5-HT1F, 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, 5-HT3A, 5-HT2B, 5-HT2C, and 5-HT7, as well as rat α1-adrenergic and rat α2-adrenergic receptors with Kis of 0.006, 0.530, 0.549, 0.575, 1.415, 3.935, 1.695, 3.499, 4.851, 5.06 and 3.69 μM, respectively[1]. LY 344864 is a inducer of mitochondrial biogenesis[2].
|
| ln Vivo |
LY 344864 (0-10 ng/kg; p.o. or i.v.; once) inhibits neurogenic dural inflammation in rat migraine pain model[1].
LY 344864 (1 mg/kg; intravenously; once) can partially penetrate the blood-brain barrier in rats[1]. LY 344864 (2 mg/kg; i.p.; daily for 14 days) reduces the loss of dopaminergic neurons and improves behavioral endpoints in a Parkinson’s disease mouse model[2]. In naive mice, daily intraperitoneal administration of LY344864 (2 mg·kg⁻¹) for 14 days increased mitochondrial DNA (mtDNA) content and mRNA expression of cytochrome c oxidase 1 (COX1) in the striatum and substantia nigra, and increased peroxisomal proliferator γ coactivator-1α (PGC-1α) mRNA expression in the striatum, indicating enhanced mitochondrial biogenesis (MB). No change in locomotor activity was observed. [2] In a mouse model of Parkinson's disease induced by bilateral intrastriatal 6-hydroxydopamine (6-OHDA) lesions, daily treatment with LY344864 (2 mg·kg⁻¹, i.p.) starting 7 days post-lesion for 14 days attenuated the loss of tyrosine hydroxylase immunoreactivity (TH-ir) in the striatum and substantia nigra pars compacta compared to vehicle-treated lesioned animals. LY344864 treatment also increased the number of TH-positive neurons in the substantia nigra and improved spontaneous locomotor activity (increased total distance travelled and vertical activity) in 6-OHDA-lesioned mice. [2] LY344864 treatment restored mtDNA content in the substantia nigra of 6-OHDA-lesioned mice to control levels and increased mRNA expression of PGC-1α, NDUFS1, ND1, and COX1 in the hippocampus and frontal cortex. Increased protein expression of PGC-1α and mitochondrial transcription factor A (TFAM) was observed in the striatum and substantia nigra of LY344864-treated lesioned mice. [2] |
| Animal Protocol |
Male Wistar rats, migraine pain model
1-10 ng/kg (oral), 0.3-2 ng/kg (intravenous) Oral, 75 minutes before trigeminal stimulation or intravenous, 10 minutes before trigeminal stimulation Three-month-old male wild-type C57Bl/6 mice were used. [2] For naive studies, mice received daily intraperitoneal injections of either LY344864 (2 mg·kg⁻¹) or saline (vehicle) for 14 days. [2] For Parkinson's disease model studies, mice underwent bilateral intrastriatal injections of 6-OHDA (5 µg per site in 0.9% NaCl with 0.02% ascorbate) under anesthesia to induce a progressive lesion of nigrostriatal dopaminergic neurons. [2] Seven days post-lesion, mice began daily intraperitoneal treatment with either LY344864 (2 mg·kg⁻¹) or vehicle for 14 days. [2] Locomotor activity was assessed before lesioning, 7 days post-lesion, and after the 14-day treatment period using an automated activity monitoring system. [2] After treatment, mice were euthanized, and brain regions (frontal cortex, striatum, hippocampus, substantia nigra) were collected for molecular, biochemical, and immunohistochemical analyses. [2] |
| ADME/Pharmacokinetics |
In a previously cited characterization study, after a single intravenous injection of LY344864 (1 mg·kg⁻¹) into rats, the drug concentrations in plasma and brain tissue exceeded the EC50 of the compound for at least 8 hours. After 8 hours, the plasma drug concentration decreased by approximately 85% (from 260 nM to 40 nM), while the drug concentration in brain tissue remained at around 60 nM. [2]
|
| References |
|
| Additional Infomation |
LY344864 is a selective 5-HT1F receptor agonist. [2] Stimulation of the 5-HT1F receptor by LY344864 induces mitochondrial biosynthesis (MB). [2] In Parkinson's disease, LY344864-induced MB is considered a therapeutic strategy to compensate for mitochondrial dysfunction, reduce dopaminergic neuron loss, and improve motor function. [2] This study suggests that the 5-HT1F receptor is a novel therapeutic target for Parkinson's disease. [2]
|
| Molecular Formula |
C21H23CLFN3O
|
|---|---|
| Molecular Weight |
387.878227472305
|
| Exact Mass |
387.15
|
| Elemental Analysis |
C, 65.03; H, 5.98; Cl, 9.14; F, 4.90; N, 10.83; O, 4.12
|
| CAS # |
1217756-94-9
|
| Related CAS # |
LY 344864; 186544-26-3; LY 344864 S-enantiomer; 186544-27-4; LY 344864 racemate; 186543-64-6
|
| PubChem CID |
56972176
|
| Appearance |
Solid powder
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
3
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
27
|
| Complexity |
506
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
CN(C)[C@@H]1CCC2=C(C1)C3=C(N2)C=CC(=C3)NC(=O)C4=CC=C(C=C4)F.Cl
|
| InChi Key |
OKUHLSYESBLBCP-PKLMIRHRSA-N
|
| InChi Code |
InChI=1S/C21H22FN3O.ClH/c1-25(2)16-8-10-20-18(12-16)17-11-15(7-9-19(17)24-20)23-21(26)13-3-5-14(22)6-4-13;/h3-7,9,11,16,24H,8,10,12H2,1-2H3,(H,23,26);1H/t16-;/m1./s1
|
| Chemical Name |
N-[(6R)-6-(dimethylamino)-6,7,8,9-tetrahydro-5H-carbazol-3-yl]-4-fluorobenzamide;hydrochloride
|
| Synonyms |
LY-344864 HCl; LY344864; LY 344864; LY-344864 hydrochloride; LY-344864
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5781 mL | 12.8906 mL | 25.7812 mL | |
| 5 mM | 0.5156 mL | 2.5781 mL | 5.1562 mL | |
| 10 mM | 0.2578 mL | 1.2891 mL | 2.5781 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA