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.
Physicochemical Properties
| 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) |
Biological Activity
| 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 ) |
| 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]. |
| 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 |
| References |
[1]. Characterization of LY344864 as a pharmacological tool to study 5-HT1F receptors: binding affinities, brain penetration and activity in the neurogenic dural inflammation model of migraine. Life Sci. 1997;61(21):2117-26. [2]. 5-HT1F receptor-mediated mitochondrial biogenesis for the treatment of Parkinson's disease. Br J Pharmacol. 2018 Jan;175(2):348-358. |
Solubility Data
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (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 |